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If Hannah has been taking ketoconazole to treat athlete's foot for 6 weeks, until today, she will be eligible for the primary trial next Tuesday. | Exclusion Criteria:
Use of any of these medications within 4 weeks; cyclosporine, diltiazen, ketoconazole, rifampin, fluconazole, delavirdine, nicardipine, pioglitazone, and sulfonamides, erythromycin, clarithromycin, itraconazole, erythromycin, metoclopramide, nevirapine, phenobarbital, phenytoin, indinavir, fosamprenavir, nefazadone, St Johns Wort. | Contradiction |
Neither the primary trial or the secondary trial use Low Dose Magnesium Oxide, Biopsies or Mometasone in their intervention. | INTERVENTION 1:
Moderated Group
one 12-week online support group led by a professional healthcare provider
INTERVENTION 2:
Non-facilitated (Peer-led)
12-week online support in a peer-led format
INTERVENTION 1:
Sentinel Lymph Node Biopsy With Radiolabeled Methylene Blue
One arm diagnostic using 1 mCi of 125-I Methylene blue dye to find sentinel lymph nodes | Contradiction |
Between both of the patient cohorts of the primary trial and the secondary trial there was only a single patient with a deficiency of granulocytes in the blood. | Adverse Events 1:
Total: 56/199 (28.14%)
AGRANULOCYTOSIS 1/199 (0.50%)
ANAEMIA 1/199 (0.50%)
BONE MARROW FAILURE 1/199 (0.50%)
FEBRILE NEUTROPENIA 11/199 (5.53%)
LEUKOPENIA 1/199 (0.50%)
NEUTROPENIA 1/199 (0.50%)
PANCYTOPENIA 1/199 (0.50%)
ACUTE MYOCARDIAL INFARCTION 1/199 (0.50%)
ATRIAL FLUTTER 1/199 (0.50%)
ATRIAL THROMBOSIS 0/199 (0.00%)
CARDIAC FAILURE 3/199 (1.51%)
Adverse Events 2:
Total: 66/198 (33.33%)
AGRANULOCYTOSIS 0/198 (0.00%)
ANAEMIA 0/198 (0.00%)
BONE MARROW FAILURE 0/198 (0.00%)
FEBRILE NEUTROPENIA 27/198 (13.64%)
LEUKOPENIA 0/198 (0.00%)
NEUTROPENIA 2/198 (1.01%)
PANCYTOPENIA 1/198 (0.51%)
ACUTE MYOCARDIAL INFARCTION 0/198 (0.00%)
ATRIAL FLUTTER 0/198 (0.00%)
ATRIAL THROMBOSIS 1/198 (0.51%)
CARDIAC FAILURE 4/198 (2.02%)
Adverse Events 1:
Total: 3/8 (37.50%)
Anaemia 0/8 (0.00%)
Febrile neutropenia 0/8 (0.00%)
Polycythaemia 0/8 (0.00%)
Acute coronary syndrome 0/8 (0.00%)
Vertigo 0/8 (0.00%)
Eyelid oedema 1/8 (12.50%)
Constipation 0/8 (0.00%)
Diarrhoea 0/8 (0.00%)
Nausea 0/8 (0.00%)
Stomatitis 0/8 (0.00%)
Upper gastrointestinal haemorrhage 0/8 (0.00%)
Vomiting 0/8 (0.00%)
Chest pain 0/8 (0.00%)
Adverse Events 2:
Total: 2/6 (33.33%)
Anaemia 0/6 (0.00%)
Febrile neutropenia 0/6 (0.00%)
Polycythaemia 0/6 (0.00%)
Acute coronary syndrome 0/6 (0.00%)
Vertigo 0/6 (0.00%)
Eyelid oedema 0/6 (0.00%)
Constipation 0/6 (0.00%)
Diarrhoea 0/6 (0.00%)
Nausea 0/6 (0.00%)
Stomatitis 0/6 (0.00%)
Upper gastrointestinal haemorrhage 0/6 (0.00%)
Vomiting 0/6 (0.00%)
Chest pain 1/6 (16.67%) | Entailment |
Patients participating in the primary trial and the secondary trial experienced serious eye disorders. | Adverse Events 1:
Total: 1/3 (33.33%)
Pericardial effusion [1]0/3 (0.00%)
Abdominal muscle wall hemorrhage [2]0/3 (0.00%)
Dehydration [3]0/3 (0.00%)
Gastroenteritis 0/3 (0.00%)
Dehydration 0/3 (0.00%)
Vomiting [4]0/3 (0.00%)
Colonic perforation [5]0/3 (0.00%)
Abdominal pain 0/3 (0.00%)
Chemical meningitis 0/3 (0.00%)
Lung infection 0/3 (0.00%)
Wound infection 0/3 (0.00%)
Adverse Events 2:
Total: 2/3 (66.67%)
Pericardial effusion [1]0/3 (0.00%)
Abdominal muscle wall hemorrhage [2]0/3 (0.00%)
Dehydration [3]0/3 (0.00%)
Gastroenteritis 0/3 (0.00%)
Dehydration 0/3 (0.00%)
Vomiting [4]0/3 (0.00%)
Colonic perforation [5]0/3 (0.00%)
Abdominal pain 0/3 (0.00%)
Chemical meningitis 0/3 (0.00%)
Lung infection 0/3 (0.00%)
Wound infection 1/3 (33.33%)
Adverse Events 1:
Total: 148/1755 (8.43%)
Anaemia * 1/1755 (0.06%)
Neutropenia * 0/1755 (0.00%)
Thrombocytopenia * 0/1755 (0.00%)
Thrombocytopenic purpura * 1/1755 (0.06%)
Acute cardiac event * 1/1755 (0.06%)
Aortic valve incompetence * 1/1755 (0.06%)
Arrhythmia * 1/1755 (0.06%)
Atrial fibrillation * 1/1755 (0.06%)
Cardiac failure * 0/1755 (0.00%)
Cardiac tamponade * 0/1755 (0.00%)
Adverse Events 2:
Total: 64/868 (7.37%)
Anaemia * 2/868 (0.23%)
Neutropenia * 2/868 (0.23%)
Thrombocytopenia * 1/868 (0.12%)
Thrombocytopenic purpura * 0/868 (0.00%)
Acute cardiac event * 0/868 (0.00%)
Aortic valve incompetence * 0/868 (0.00%)
Arrhythmia * 1/868 (0.12%)
Atrial fibrillation * 0/868 (0.00%)
Cardiac failure * 1/868 (0.12%)
Cardiac tamponade * 1/868 (0.12%) | Contradiction |
Patients with severe malabsorption disorders are ineligible for the primary trial, unless they are able to receive intravenous (IV) alimentation. | Patients with any of the following conditions or complications are NOT eligible for participation:
Require intravenous (IV) alimentation
Malabsorption syndrome | Contradiction |
Patients receiving intervention 1 of the primary trial, will be administered medication orally and intraveinously. | INTERVENTION 1:
Arm A : iv Vinflunine Plus Capecitabine
Vinflunine dose 280 mg/m² on day 1 of each cycle every 3 weeks, Capecitabine 825 mg/m² twice daily orally for 14 consecutive days beginning on day 1 of each cycle followed by 1 week of rest.
vinflunine: intraveinous administration day 1 once every 3 weeks, 280 mg/m²
Capecitabine: Arm A : 1650 mg/m² Arm B : 2500 mg/m²
INTERVENTION 2:
Arm B : Capecitabine
1250 mg/m² twice daily orally for 14 consecutive days beginning on day 1 of each cycle followed by 1 week of rest
Capecitabine: Arm A : 1650 mg/m² Arm B : 2500 mg/m² | Entailment |
Two dozen the primary trial participants are classified as having Pathologic Complete Response (pCR) in the Breast and Nodes. | Outcome Measurement:
Number of Participants With Pathologic Complete Response (pCR) in the Breast and Nodes
pCR was defined as no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel node identified after neoadjuvant chemotherapy.
Time frame: From the start of the study until the time of surgery (average of 221.9 days [standard deviation of 23.65 days] after study entry)
Results 1:
Arm/Group Title: AC, Followed by Weekly Paclitaxel and Concurrent Pazopanib
Arm/Group Description: Participants were treated with intravenous (IV) doxorubicin (60 milligrams per meters squared [mg/m^2]) and cyclophosphamide (AC) (600 mg/m^2) every 21 days for 4 cycles. This was followed by weekly paclitaxel (WP) 80 mg/m^2 IV on Days 1, 8, and 15 every 28 days for 4 cycles given concurrently with oral pazopanib 800 mg (2 tablets taken at the same time each day, either 1 hour before or 2 hours after a meal) taken daily and continuing until 7 days before surgery. Pazopanib was resumed at the same oral dose 4-6 weeks after surgery and was continued daily for 6 months.
Overall Number of Participants Analyzed: 93
Measure Type: Number
Unit of Measure: Participants 16 | Contradiction |
There were no cases of Leukopenia, Epitasis or Arrhythmia observed in patients participating in the primary trial. | Adverse Events 1:
Total: 18/26 (69.23%)
Thrombocytopenia * 4/26 (15.38%)
Neutropenia * 3/26 (11.54%)
Epitasis * 1/26 (3.85%)
Peripheral arterial ischemia * 1/26 (3.85%)
Thrombosis * [1]1/26 (3.85%)
Weakness * 1/26 (3.85%)
Pain * [2]2/26 (7.69%)
Febrile neutropenia * 1/26 (3.85%)
Aspartate Aminotransferase * [3]1/26 (3.85%)
Syncope * 1/26 (3.85%) | Contradiction |
Candidates for the primary trial must have a bone density scan 1 month prior to study entry, if the results from this are more than 2 standard deviations below normal, the study physician can still decide to let them participate. | Bone density scan within 2 standard deviations from normal within the past 30 days
Bone density scan 2 standard deviations below normal allowed if approved by the study physician | Entailment |
There were no patients in either cohort of the primary trial with a PFS exceeding one year. | Outcome Measurement:
Progression Free Survival (PFS)
PFS was assessed by the investigator based on World Health Organization (WHO) criteria using radiographic tumor evaluations. Disease progression was defined as the appearance of any new lesion not previously identified or an estimated increase of 25% or more in existent bidimensionally or unidimensionally measurable lesions or progression of an existing non-measurable lesion. For bidimensionally measurable malignant lesions with an area of at least 2.0 centimeters squared (cm^2) an increase of 1.0 cm^2 was required and for unidimensionally measurable lesions of 1.0 cm or less an increase of 0.5 cm was required. PFS was defined as the number of days between date of randomization and date of documented disease progression or date of death. Kaplan Meier estimates of PFS are presented.
Time frame: 24 Months, End of Study (Up to 5 years)
Results 1:
Arm/Group Title: Trastuzumab + Anastrozole
Arm/Group Description: Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.
Overall Number of Participants Analyzed: 103
Median (95% Confidence Interval)
Unit of Measure: Months 24 Months: 4.8 (3.7 to 7)
End of Study: 5.8 (4.6 to 8.3)
Results 2:
Arm/Group Title: Anastrozole
Arm/Group Description: 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.
Overall Number of Participants Analyzed: 104
Median (95% Confidence Interval)
Unit of Measure: Months 24 Months: 2.4 (2 to 4.6)
End of Study: 2.9 (2.1 to 4.5) | Entailment |
the primary trial and the secondary trial both administer Zometa to their patients through IV, although in different doses. | INTERVENTION 1:
Treatment (MEDI4736, Tremelimumab)
Patients receive anti-B7H1 monoclonal antibody MEDI4736 IV over 1 hour and tremelimumab IV over 1 hour on day 1. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Four weeks after the last combination dose, patients continue to receive anti-B7H1 monoclonal antibody MEDI4736 every 2 weeks for up to 18 additional doses in the absence of disease progression or unacceptable toxicity. Patients achieving PD or clinical benefit (CR, PR, or SD) may be retreated with anti-B7H1 monoclonal antibody MEDI4736 for an additional 52 weeks.
Anti-B7H1 Monoclonal Antibody MEDI4736: Given IV
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Tremelimumab: Given IV
INTERVENTION 1:
Zoledronic Acid 5 mg IV
Zometa (Zoledronic Acid) 5 mg IV given over 15 minutes as a one time dose. Follow-up at month 1 & every 2 months to month 12 for serum & urine markers of bone destruction (NTx & CTx). | Contradiction |
One patient in the primary trial had a 2.87 cm3 decrease in Total MRI Functional Tumor Volume (FTV) over 3 months. | Outcome Measurement:
Mean Total MRI Functional Tumor Volume (FTV) Change From Baseline to Month 3 (V3)
Mean total MRI FTV change from baseline to month 3 (V3): For patients with more than one measureable lesion on the MRI, the sum over all measureable lesions on the MRI was calculated at each time point. V3 was calculated by subtracting the total MRI FTV measured (i.e. the sum over all lesions present with MRI FTV measurements) at 3 months from the total MRI FTV measured at baseline. For V3 the raw change in the volume will be calculated for each patient and a mean and 95% confidence interval will be constructed using two-sided t-tests.
Time frame: up to 3 months from start of treatment
Results 1:
Arm/Group Title: Letrozole + MRI
Arm/Group Description: Protocol Therapy will consist of 6 months of letrozole, administered orally at a dose of 2.5 mg/day. Patients will have a bilateral MRI for disease evaluation at months 3 and 6.
Overall Number of Participants Analyzed: 68
Mean (95% Confidence Interval)
Unit of Measure: cubic centimeters -1.93 (-2.87 to -0.98) | Entailment |
Patient who have recently undergone External beam radiation therapy are eligible for the primary trial. | Inclusion Criteria:
Patients may have received prior radiation therapy | Entailment |
the primary trial treament last for a shorter period of time than the secondary trial treatment, but is administered much more often. | INTERVENTION 1:
Accelerated Partial Breast Brachytherapy
Each patient will receive accelerated partial breast brachytherapy with multiple plane implant.
Patients will receive 3400 cGy delivered in 10 twice-daily fractions. Treatment is to be given over 5-7 days with a minimum of 6 hours separation between fractions.
INTERVENTION 1:
Arm I (Cranial Microcurrent Electrical Stimulation [CES])
Patients receive a CES unit (Alpha-Stim® 100 Microcurrent Stimulator) that passes microcurrent levels of biphasic electrical stimulation via ear-lobe electrodes. The CES unit is preset to provide 1 hour of 100 μA (sub-sensory level), modified square-wave biphasic stimulation on a 50% duty cycle at .05 Hz, and to automatically turn off at the end of 1 hour. Patients use their CES unit once daily in weeks 1-18.
energy-based therapy: Given once a day for 18 weeks | Contradiction |
Cohort 1 of the primary trial reported one case of AML. | Adverse Events 1:
Total: 4/26 (15.38%)
Disseminated intravascular coagulation 1/26 (3.85%)
Cardiac failure congestive 1/26 (3.85%)
Breast cellulitis 1/26 (3.85%)
Cellulitis 1/26 (3.85%)
Acute myeloid leukaemia 1/26 (3.85%)
Seizure 0/26 (0.00%)
Pulmonary embolism 1/26 (3.85%) | Entailment |
There are no racial criteria for entry into the primary trial, however there are gender criteria. | INCLUSION CRITERIA
Males and Females 18 years old diagnosed with HER2 positive breast cancer
Scheduled to receive neoadjuvant or adjuvant trastuzumab (Herceptin®) therapy (anthracycline-containing regimens are permitted). Patients receiving Herceptin® with their chemotherapy are permitted for eligibility work-up. Taxanes are permitted. Trastuzumab (Herceptin®) therapy may be given with or after primary chemotherapy. Pertuzumab may be used in conjunction with trastuzumab.
Left Ventricular Ejection Fraction (LVEF) 50% by MUGA scan or echocardiogram
Adequate renal function for administration of trastuzumab-containing chemotherapy regimen.
Sitting systolic blood pressure of > 90 mm Hg
Pulse 60 beats/minute
Not pregnant or breastfeeding
Female patients of childbearing potential, who are sexually active, must have a negative pregnancy test before starting the study
Both men and women must be willing to use effective contraception during the study. Teratogenicity is documented for both active study agents
Able to swallow capsules
EXCLUSION CRITERIA:
Patients with metastatic disease
Prior treatment with trastuzumab or anthracyclines prior to this chemotherapy regimen
Current treatment with angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), such as losartan, β-blockers or digoxin
Known cardiac history: heart failure, myocardial infarction, radiation-induced cardiac dysfunction
Known allergy to either ACE inhibitors or β-blockers
History of bronchial asthma or related bronchospastic conditions
Hereditary or idiopathic angioedema
History of severe hypersensitivity reactions to drugs or other causes, i.e. bee stings
This protocol does not exclude patients who are participating on other investigational studies. Refer to the local IRB guidelines. | Contradiction |
Patients with hemophilia are excluded from the primary trial. | Exclusion Criteria:
active bleeding or a pathological condition that carries a high risk of bleeding | Entailment |
Patients with tumors underexpressing HER2 are excluded from the primary trial, but may be included in the secondary trial. | Inclusion Criteria:
HER-2/neu 1+ or 2+ by immunohistochemistry
Inclusion Criteria:
At least 18 years of age
Willing and able to provide informed consent
Reporting daily hot flashes
Able to read, write, and speak English
Postmenopausal to limit sample variability (> 12 months amenorrhea)
Greater then 1 month but < 5 years post-treatment (surgery, radiation, chemotherapy) for non-metastatic breast cancer.
These criteria allow inclusion of women successfully treated for recurrent breast cancer since there is no known reason to exclude them. Menopausal status is assessed using self-reports due to problems in reliably measuring follicle-stimulating hormone levels and estradiol in tamoxifen users.
Exclusion Criteria:
Exclusion criteria are current depression, history of migraines or hepatitis, abnormal chemistry profile (e.g., sodium, potassium, glucose), or a positive urine drug screen for illegal substances. | Entailment |
Candidates for the primary trial are expected to be capable of holding their breath for half a minute. | Inclusion Criteria:
Patient must be able to maintain a 30 second breath hold. | Entailment |
Patients with Breast cancers that have estrogen receptors are excluded from the primary trial. | Inclusion Criteria:
Patients with node-negative, ER or PR-positive tumors 4 cm in size whose tumors are low risk (defined as a score of 0-17) on an Oncotype DX profile are not eligible. | Entailment |
the primary trial and the secondary trial do not use the same route of administration for their interventions. | INTERVENTION 1:
Treatment (Vaccine Therapy+ex Vivo-expanded T Cells)
Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) ID on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to isolate and collect peripheral blood mononuclear cells for T-cell expansion.
Patients receive cyclophosphamide IV once on day -1 and autologous ex vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10 days for up to three immunizations. Patients receive a booster HER2/neu peptide vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.
HER-2/neu peptide vaccine: Given ID
leukapheresis: Undergo leukapheresis
ex vivo-expanded HER2-specific T cells: Given IV
cyclophosphamide: Given IV
sargramostim: Given ID
laboratory biomarker analysis: Correlative study
INTERVENTION 1:
PET Guided Biopsy
No comparison group. All enrolled participants were expected to undergo PET guided biopsy. | Entailment |
There were more cases of Febrile neutropenia than eukopenia observed in the primary trial, but less cases of Febrile neutropenia than Neutropenia. | Adverse Events 1:
Neutropenia 14/373 (3.75%)
Febrile neutropenia 10/373 (2.68%)
Leukopenia 1/373 (0.27%) | Entailment |
the primary trial patients receive Trametinib, Akt Inhibitor GSK2141795 PO QD on days 1-28, up to a maximum of 8 cycles. | INTERVENTION 1:
Study Participants
There are no arms or subgroups in this study. | Contradiction |
the route of administration for both interventions in the primary trial is a topical skin cream. | INTERVENTION 1:
Celecoxib
Randomized to receive celecoxib daily for 12 months
INTERVENTION 2:
Placebo
Randomized to receive placebo daily for 12 months | Contradiction |
One patient in the primary trial was observed suffering from Enteritis. | Adverse Events 1:
Total: 12/66 (18.18%)
Palpitations * 1/66 (1.52%)
Haematemesis * 1/66 (1.52%)
Performance status decreased * 1/66 (1.52%)
Hepatic failure * 1/66 (1.52%)
Cellulitis * 1/66 (1.52%)
Device related infection * 1/66 (1.52%)
Pneumonia * 1/66 (1.52%)
Pneumonia pneumococcal * 1/66 (1.52%)
Femur fracture * 0/66 (0.00%)
Hypokalaemia * 1/66 (1.52%)
Back pain * 2/66 (3.03%) | Contradiction |
Unlike the secondary trial, the primary trial does not provide a duration of cycles or any dosages in the intervention section. | INTERVENTION 1:
CMRM vs UMRM
[Not Specified]
INTERVENTION 1:
A: Exemestane
ARM A: Patients will be treated with exemestane.
Exemestane: 25 mg daily by mouth for 6 to 12 months.
INTERVENTION 2:
B: Docetaxel and Cytoxan
ARM B: Patients will be treated with docetaxel and cytoxan.
Docetaxel: Docetaxel (75 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks).
Cytoxan: Cytoxan (600 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks). | Entailment |
1 patient in the primary trial had a cardiac related adverse event. | Adverse Events 1:
Total: 146/573 (25.48%)
Anaemia 4/573 (0.70%)
Disseminated intravascular coagulation 0/573 (0.00%)
Neutropenia 1/573 (0.17%)
Thrombocytopenia 0/573 (0.00%)
Acute coronary syndrome 1/573 (0.17%)
Angina pectoris 1/573 (0.17%)
Atrial fibrillation 2/573 (0.35%)
Atrial flutter 0/573 (0.00%)
Cardiac arrest 1/573 (0.17%)
Cardiac failure 0/573 (0.00%)
Adverse Events 2:
Total: 101/570 (17.72%)
Anaemia 3/570 (0.53%)
Disseminated intravascular coagulation 1/570 (0.18%)
Neutropenia 1/570 (0.18%)
Thrombocytopenia 1/570 (0.18%)
Acute coronary syndrome 0/570 (0.00%)
Angina pectoris 1/570 (0.18%)
Atrial fibrillation 0/570 (0.00%)
Atrial flutter 1/570 (0.18%)
Cardiac arrest 0/570 (0.00%)
Cardiac failure 1/570 (0.18%) | Contradiction |
the primary trial had three times the occurence rate of fistula enterovesical as the secondary trial. | Adverse Events 1:
fistula enterovesical 1/74 (1.35%)
Adverse Events 1:
Total: 11/50 (22.00%)
Anemia 3/50 (6.00%)
Febrile neutropenia 1/50 (2.00%)
Arrythmia 1/50 (2.00%)
Ileus 1/50 (2.00%)
Nausea 1/50 (2.00%)
Pain-Abdominal 1/50 (2.00%)
Vomiting 1/50 (2.00%)
Bronchial infection 1/50 (2.00%)
Sepsis 1/50 (2.00%)
Neutropenia 2/50 (4.00%)
Platelet count decreased 1/50 (2.00%)
Dehydration 1/50 (2.00%)
Arthralgia 1/50 (2.00%) | Contradiction |
There were several patients who contracted Pneumonia in the primary trial. | Adverse Events 1:
Total: 20/52 (38.46%)
Febrile bone marrow aplasia * 5/52 (9.62%)
Febrile neutropenia * 6/52 (11.54%)
Leukopenia * 6/52 (11.54%)
Atrial tachycardia * 1/52 (1.92%)
Vomiting * 1/52 (1.92%)
Tooth loss * 1/52 (1.92%)
Hyperthermia * 1/52 (1.92%)
Malaise * 1/52 (1.92%)
Pyrexia * 1/52 (1.92%)
Impaired healing * 3/52 (5.77%)
Inflammation * 1/52 (1.92%) | Contradiction |
the primary trial and the secondary trial observed a different number of adverse events in their patients. | Adverse Events 1:
Total: 25/60 (41.67%)
Anaemia * 1/60 (1.67%)
Febrile neutropenia * 2/60 (3.33%)
Idiopathic thrombocytopenic purpura * 1/60 (1.67%)
Thrombocytopenia * 3/60 (5.00%)
Cardiac failure * 1/60 (1.67%)
Cardiac failure acute * 1/60 (1.67%)
Cardiogenic shock * 1/60 (1.67%)
Left ventricular dysfunction * 1/60 (1.67%)
Anal fistula * 1/60 (1.67%)
Adverse Events 1:
Total: 4/26 (15.38%)
Febrile neutropenia * 1/26 (3.85%)
Gastric volvulus * 20/26 (0.00%)
General Malaise * 21/26 (3.85%)
Hospitalisation for intrapleuric chemotherapy and thoracentesis * 21/26 (3.85%)
Acute renal failure * 21/26 (3.85%) | Entailment |
Women with chronic obstructive pulmonary disease that do not require systemic corticosteroids, are eligible for the primary trial. | No prior or currently active autoimmune disease requiring management with systemic immunosuppression. This includes inflammatory bowel disease, systemic vasculitis, scleroderma, psoriasis, multiple sclerosis, hemolytic anemia or immune-mediated thrombocytopenia, rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, sarcoidosis, or other rheumatologic disease. Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids is acceptable. | Entailment |
the primary trial recorded more seizures than the secondary trial, despite having less than one tenth the number of patients in its total cohort. | Adverse Events 1:
Seizure 1/38 (2.63%)
Adverse Events 1:
Total: 92/490 (18.78%)
Anaemia * 1/490 (0.20%)
Anaemia of malignant disease * 0/490 (0.00%)
Febrile neutropenia * 0/490 (0.00%)
Neutropenia * 0/490 (0.00%)
Thrombocytopenia * 4/490 (0.82%)
Angina pectoris * 0/490 (0.00%)
Atrial fibrillation * 1/490 (0.20%)
Cardiomyopathy * 1/490 (0.20%)
Coronary artery disease * 0/490 (0.00%)
Pericardial effusion * 0/490 (0.00%)
Adverse Events 2:
Total: 99/488 (20.29%)
Anaemia * 1/488 (0.20%)
Anaemia of malignant disease * 1/488 (0.20%)
Febrile neutropenia * 2/488 (0.41%)
Neutropenia * 1/488 (0.20%)
Thrombocytopenia * 1/488 (0.20%)
Angina pectoris * 1/488 (0.20%)
Atrial fibrillation * 0/488 (0.00%)
Cardiomyopathy * 0/488 (0.00%)
Coronary artery disease * 1/488 (0.20%)
Pericardial effusion * 2/488 (0.41%) | Entailment |
In total more participants in the primary trial had no tumor Response, than partial response, and only 3 patients had a complete response. | Outcome Measurement:
Number of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR), as Assessed by the Independent Review Committee (IRC)
OR is defined as the number of participants achieving either a confirmed CR or PR, per Response Evaluation Criteria in Solid Tumors (RECIST, v 1.0). Best OR is defined as the best response recorded from the start of treatment until progressive disease (PD)/recurrence. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of TLs, taking as a reference the Baseline sum LD and no PD, or complete resolution of TLs and the persistence of one or more non-TL(s), as assessed by the IRC. PD is defined as at least a 20% increase in the sum of the LD of TLs, taking as a reference the smallest sum LD recorded since the treatment started or the appearance of >= 1 new lesions or unequivocal progression of existing non-TLs. Responses were confirmed at subsequent assessments made >=28 days after the original response. Participants with an unknown or missing response are treated as non-responders.
Time frame: From the date of the first dose of investigational product to the first documented evidence of a confirmed CR or PR (up to Study Week 103)
Results 1:
Arm/Group Title: Lapatinib 1500 mg QD
Arm/Group Description: Participants received lapatinib 1500 mg orally QD. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Overall Number of Participants Analyzed: 69
Measure Type: Number
Unit of Measure: Participants CR: 0
PR: 15
Results 2:
Arm/Group Title: Lapatinib 500 mg BID
Arm/Group Description: Participants received lapatinib 500 mg orally BID. Treatment was continued for 12 weeks or until disease progression or withdrawal from treatment for another reason. After Week 12, participants with clinical benefit had the option to continue with the lapatinib therapy at the same dose and schedule, until disease progression, provided the treatment was tolerated.
Overall Number of Participants Analyzed: 69
Measure Type: Number
Unit of Measure: Participants CR: 0
PR: 18 | Contradiction |
the secondary trial and the primary trial interventions both require subjects to follow caloric restricted diets or gluten free diets, while completing food diaries. | INTERVENTION 1:
Lapatinib Plus Capecitabine
Participants received a daily dose of 5 tablets of lapatinib (1250 mg) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg/m^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
INTERVENTION 2:
Trastuzumab Plus Capecitabine
Participants received an IV infusion of trastuzumab 8 mg/kg on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
INTERVENTION 1:
Behavioral Dietary Intervention
Beginning 2-4 weeks after completion of lumpectomy, patients receive food diaries to complete for 7-10 days. Dietary counselors then give patients guidelines for dietary modifications to reduce caloric intake by 25% of their normal diet. Patients follow caloric restricted diet for 10 weeks (2 weeks prior to radiation therapy, during 6 weeks of radiation therapy, and at least 2 weeks after radiation therapy). Patients undergo radiation therapy QD 5 days a week for 6 weeks.
Behavioral dietary intervention: Receive caloric restricted dietary intervention
Therapeutic conventional surgery: Undergo definitive lumpectomy
Radiation therapy: Undergo radiation therapy
Counseling intervention: Receive dietary counseling
Quality-of-life assessment: Ancillary studies | Contradiction |
Abnormal LVEF, Pregnancy or lactating automatically eliminates patients from participating in the primary trial, unless treated with herbal medicines. | All herbal (alternative) medicines are prohibited.
EXCLUSION CRITERIA
Congestive heart failure, abnormal left ventricular ejection fraction (LVEF), angina pectoris, uncontrolled cardiac arrhythmias, or other significant heart disease, or who have had a myocardial infarction within the past year.
Pregnant or lactating | Contradiction |
Throughout both the secondary trial and the primary trial there was only one case of pregnancy, in cohort 1 of the secondary trial. | Adverse Events 1:
Total: 17/145 (11.72%)
ANAEMIA 0/145 (0.00%)
LEUKOPENIA 2/145 (1.38%)
NEUTROPENIA 1/145 (0.69%)
LEUKOCYTOSIS 1/145 (0.69%)
THROMBOCYTOPENIA 1/145 (0.69%)
FEBRILE NEUTROPENIA 1/145 (0.69%)
THROMBOTIC THROMBOCYTOPENIC PURPURA 0/145 (0.00%)
DISSEMINATED INTRAVASCULAR COAGULATION 0/145 (0.00%)
CARDIAC FAILURE 1/145 (0.69%)
ATRIAL FIBRILLATION 1/145 (0.69%)
Adverse Events 2:
Total: 11/144 (7.64%)
ANAEMIA 1/144 (0.69%)
LEUKOPENIA 0/144 (0.00%)
NEUTROPENIA 0/144 (0.00%)
LEUKOCYTOSIS 0/144 (0.00%)
THROMBOCYTOPENIA 0/144 (0.00%)
FEBRILE NEUTROPENIA 1/144 (0.69%)
THROMBOTIC THROMBOCYTOPENIC PURPURA 1/144 (0.69%)
DISSEMINATED INTRAVASCULAR COAGULATION 1/144 (0.69%)
CARDIAC FAILURE 0/144 (0.00%)
ATRIAL FIBRILLATION 0/144 (0.00%)
Adverse Events 1:
Total: 22/79 (27.85%)
Anaemia 0/79 (0.00%)
Right ventricular dysfunction 1/79 (1.27%)
Diarrhoea 1/79 (1.27%)
Vomiting 2/79 (2.53%)
Abdominal pain 0/79 (0.00%)
Colonic obstruction 0/79 (0.00%)
Dysphagia 1/79 (1.27%)
Nausea 1/79 (1.27%)
Mucosal inflammation 1/79 (1.27%)
Performance status decreased 1/79 (1.27%)
Sudden death 1/79 (1.27%)
Adverse Events 2:
Total: 13/76 (17.11%)
Anaemia 1/76 (1.32%)
Right ventricular dysfunction 0/76 (0.00%)
Diarrhoea 0/76 (0.00%)
Vomiting 2/76 (2.63%)
Abdominal pain 1/76 (1.32%)
Colonic obstruction 1/76 (1.32%)
Dysphagia 0/76 (0.00%)
Nausea 1/76 (1.32%)
Mucosal inflammation 0/76 (0.00%)
Performance status decreased 0/76 (0.00%)
Sudden death 0/76 (0.00%) | Contradiction |
There is no significant difference in the proportions of Subjects With Clinical Benefit in the Exemestane + Celecoxib cohort and in the Exemestane alone cohort of the primary trial. | Outcome Measurement:
Number of Subjects With Clinical Benefit
Clinical benefit was based on objective tumor assessments made according to Response Evaluation Criteria (RECIST) system of unidimensional evaluation. Includes subjects with complete response (CR), partial response (PR), and long term disease stabilization (SD) for at least 24 weeks.
Time frame: Baseline, Week 8, 16, 24, and every 12 weeks beyond 24 up to Week 108 and every 24 weeks thereafter until 9 months following last subject last visit (LSLV)
Results 1:
Arm/Group Title: Exemestane (Exemestane Alone)
Arm/Group Description: oral dose exemestane taken with food (25 mg tablet once daily)
Overall Number of Participants Analyzed: 49
Measure Type: Number
Unit of Measure: participants 24
Results 2:
Arm/Group Title: Combination (Exemestane + Celecoxib)
Arm/Group Description: oral doses to be taken with food (25 mg tablet exemestane once daily; celecoxib 2 x 200 mg tablets twice daily)
Overall Number of Participants Analyzed: 51
Measure Type: Number
Unit of Measure: participants 24 | Entailment |
on assessment 0 the primary trial Participants had a confirmed disappearance of all target and non-target lesions. | Outcome Measurement:
Number of Participants With Objective Response Based on Data Review Committee's Assessment
Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST). CR is defined as disappearance of all target and non-target lesions. PR is defined as 30% decrease in sum of the longest dimensions (LDs) of the target lesions taking as reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat evaluation 4 weeks after initial documentation of response.
Time frame: Day 1 of Cycle 2, every 6 weeks after Cycle 2, and at the end of Cycle 8.
Results 1:
Arm/Group Title: SUNITINIB+CAPECITABINE
Arm/Group Description: Sunitinib was administered orally from Day 1 at the starting dose of 37.5 mg/day on a continuous daily dosing schedule in 21-day cycles. Capecitabine was administered orally from Days 1 to 14 every 21 days at a starting dose of 2,000 mg/m^2/day. Participants were monitored for toxicity, and sunitinib and/or capecitabine dosing could be interrupted or reduced according to individual tolerance. Participants with progressive disease (PD) or intolerable toxicity were considered for discontinuation from the study.
Overall Number of Participants Analyzed: 63
Measure Type: Number
Unit of Measure: participants Total Number of Participants with CR+PR: 19
Complete Response (CR): 0
Partial Response (PR): 19 | Contradiction |
Patients who received over 5 years of anastrozole therapy, completed under a year ago, are eligible for the primary trial. | Must have received 4½ - 6 years of aromatase inhibitor therapy (e.g., letrozole, anastrozole, or exemestane), either as initial therapy or after prior tamoxifen citrate, including treatment received as part of clinical trial CAN-NCIC-MA17
Completed aromatase inhibitor therapy 2 years ago | Contradiction |
None of the adverse events which occurred in the primary trial were not GI related. | Adverse Events 1:
Total: 58/438 (13.24%)
Febrile neutropenia 13/438 (2.97%)
Neutropenia 5/438 (1.14%)
Anaemia 0/438 (0.00%)
Thrombocytopenia 0/438 (0.00%)
Haemolytic anaemia 1/438 (0.23%)
Leukopenia 1/438 (0.23%)
Cardiac failure congestive 0/438 (0.00%)
Supraventricular tachycardia 0/438 (0.00%)
Myocardial infarction 1/438 (0.23%)
Vertigo 0/438 (0.00%)
Adverse Events 2:
Total: 56/437 (12.81%)
Febrile neutropenia 10/437 (2.29%)
Neutropenia 7/437 (1.60%)
Anaemia 2/437 (0.46%)
Thrombocytopenia 1/437 (0.23%)
Haemolytic anaemia 0/437 (0.00%)
Leukopenia 0/437 (0.00%)
Cardiac failure congestive 3/437 (0.69%)
Supraventricular tachycardia 1/437 (0.23%)
Myocardial infarction 0/437 (0.00%)
Vertigo 1/437 (0.23%) | Contradiction |
Samantha has recently received a liver transplant, and is taking the combined oral contraceptive pill, she is not eligible for the primary trial, but is eligible for the secondary trial. | Exclusion criteria:
Patients with organ transplants.
Exclusion Criteria:
Current oral contraceptives | Contradiction |
The Triple-Negative Breast Cancer cohort of the primary trial had a much lower ORR than the HR+/HER2- cohort. | Outcome Measurement:
Overall Response Rate (ORR)
ORR was defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Time frame: Disease was evaluated radiologically at baseline and every 9 weeks on treatment; Maximum treatment duration was 38 cycles/26 months (Cohort 1) and 17 cycles/12 months (Cohort 2)
Results 1:
Arm/Group Title: Cohort 1: HR+/HER2-
Arm/Group Description: Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle
Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Overall Number of Participants Analyzed: 45
Measure Type: Number
Unit of Measure: percentage of participants 35.6 (24 to 49)
Results 2:
Arm/Group Title: Cohort 2: TNBC
Arm/Group Description: Eribulin: 1.4 mg/m2 administered intravenously over 2-5 minutes on days 1 and 8 of each 21 day cycle
Participants remained on single agent eribulin until disease progression or withdrawal for other reasons.
Overall Number of Participants Analyzed: 38
Measure Type: Number
Unit of Measure: percentage of participants 13.2 (5 to 26) | Entailment |
The most common adverse events in the primary trial where Infection and Stomatitis. | Adverse Events 1:
Total: 14/81 (17.28%)
Neutropenia1/81 (1.23%)
Cataract1/81 (1.23%)
Ascites1/81 (1.23%)
Gastritis Hemorrhagic1/81 (1.23%)
Nausea1/81 (1.23%)
Stomatitis2/81 (2.47%)
Malaise1/81 (1.23%)
Oedema1/81 (1.23%)
Pain1/81 (1.23%)
Pyrexia1/81 (1.23%)
Infection2/81 (2.47%)
Upper Limb Fracture1/81 (1.23%)
Dehydration1/81 (1.23%)
Hypercalcemia1/81 (1.23%) | Entailment |
There were 2 more cases of Gastrointestinal Haemorrhage in cohort 2 of the primary trial, than in cohort 1. | Adverse Events 1:
Total: 127/368 (34.51%)
ANAEMIA 3/368 (0.82%)
LEUKOPENIA 0/368 (0.00%)
NEUTROPENIA 0/368 (0.00%)
COAGULOPATHY 3/368 (0.82%)
LYMPHADENOPATHY 0/368 (0.00%)
THROMBOCYTOPENIA 2/368 (0.54%)
BONE MARROW FAILURE 0/368 (0.00%)
FEBRILE NEUTROPENIA 4/368 (1.09%)
DISSEMINATED INTRAVASCULAR COAGULATION 0/368 (0.00%)
ATRIAL FLUTTER 0/368 (0.00%)
CARDIAC ARREST 0/368 (0.00%)
Adverse Events 2:
Total: 151/369 (40.92%)
ANAEMIA 11/369 (2.98%)
LEUKOPENIA 6/369 (1.63%)
NEUTROPENIA 18/369 (4.88%)
COAGULOPATHY 0/369 (0.00%)
LYMPHADENOPATHY 1/369 (0.27%)
THROMBOCYTOPENIA 7/369 (1.90%)
BONE MARROW FAILURE 1/369 (0.27%)
FEBRILE NEUTROPENIA 15/369 (4.07%)
DISSEMINATED INTRAVASCULAR COAGULATION 1/369 (0.27%)
ATRIAL FLUTTER 1/369 (0.27%)
CARDIAC ARREST 1/369 (0.27%) | Contradiction |
There are four types of adverse events in the primary trial, for which no occurences are recorded. | Adverse Events 1:
Total: 47/254 (18.50%)
Anaemia 1/254 (0.39%)
Febrile neutropenia 1/254 (0.39%)
Lymphadenopathy 1/254 (0.39%)
Acute myocardial infarction 1/254 (0.39%)
Angina pectoris 0/254 (0.00%)
Angina unstable 0/254 (0.00%)
Bundle branch block left 0/254 (0.00%)
Cardiac failure 4/254 (1.57%)
Coronary artery disease 0/254 (0.00%)
Coronary artery stenosis 1/254 (0.39%) | Entailment |
the primary trial and the secondary trial do not employ the same route of administration for their interventions. | INTERVENTION 1:
Standard Chemotherapy
Patients receive cyclophosphamide-containing chemotherapy alone.
cyclophosphamide: Part of planned chemotherapy regimen
INTERVENTION 2:
Chemotherapy Plus Goserelin
Patients receive goserelin subcutaneously once every 4 weeks beginning 1 week before start of cyclophosphamide-containing chemotherapy. Treatment continues until completion of chemotherapy in the absence of disease progression or unacceptable toxicity.
cyclophosphamide: Part of planned chemotherapy regimen
goserelin acetate: Given subcutaneously
INTERVENTION 1:
PD-0332991 100 mg: Dose Escalation Cohort
In Phase 1-Part 1, participants received single oral dose of PD-0332991 100 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 100 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent.
INTERVENTION 2:
PD-0332991 125 mg: Dose Escalation Cohort
In Phase 1-Part 1, participants received single oral dose of PD-0332991 125 mg capsule in lead-in period (7 days prior to Cycle 1 Day 1), followed by PD-0332991 125 mg capsule orally once daily continuously for 21 days followed by 7 days off treatment in each cycle of 28 days, unless participants experienced disease progression or unacceptable toxicity or withdrew consent. | Entailment |
the primary trial participants are treated with 600 mg of Pemetrexed orally twice a month until complete response or disease progression. | INTERVENTION 1:
Pemetrexed
600 mg/m2, intravenous (IV), every 14 days until complete response or disease progression | Contradiction |
Unlike the secondary trial, the primary trial only provides the duration of cycles and drug doses in the intervention section. | INTERVENTION 1:
CMRM vs UMRM
[Not Specified]
INTERVENTION 1:
A: Exemestane
ARM A: Patients will be treated with exemestane.
Exemestane: 25 mg daily by mouth for 6 to 12 months.
INTERVENTION 2:
B: Docetaxel and Cytoxan
ARM B: Patients will be treated with docetaxel and cytoxan.
Docetaxel: Docetaxel (75 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks).
Cytoxan: Cytoxan (600 mg/m²) into a vein once every 3 weeks for 6 cycles (6 times in about 24 weeks). | Contradiction |
There less than 1% of either cohort of the primary trial was effect by Pancytopenia, but just over 5% of cohort 1 patients suffered from Coagulopathy. | Adverse Events 1:
Pancytopenia *2/425 (0.47%)
Coagulopathy *1/425 (0.24%)
Adverse Events 2:
Pancytopenia *0/406 (0.00%) | Contradiction |
Patients must have at least 3 prior treatments with trastuzumab to be eligible for the primary trial. | Inclusion Criteria:
History of trastuzumab resistance, defined as the development of progressive disease after trastuzumab-based therapy for metastatic breast cancer. Patient may not have received more than 2 prior trastuzumab-based regimens and one lapatinib-based regimen (either as single agent or in combination with chemotherapy)for metastatic breast cancer. Patients who develop metastatic disease during or after adjuvant or neoadjuvant trastuzumab are eligible. | Contradiction |
A Female patients with a mastectomy would be excluded from the primary trial. | At least 1 healthy intact breast | Contradiction |
Sarah has been experiencing epileptic seizures from a brain tumor. This will not prevent her from participating in the primary trial. | No symptomatic brain metastases | Contradiction |
Only 1 respiratory adverse event was recorded across the duration of both the secondary trial and the primary trial. | Adverse Events 1:
Total: 5/32 (15.63%)
Leukopenia 1/32 (3.13%)
Neutropenia 1/32 (3.13%)
Cataract 1/32 (3.13%)
Infection 1/32 (3.13%)
Upper respiratory tract infection 1/32 (3.13%)
Completed suicide 1/32 (3.13%)
Adverse Events 1:
Total: 4/6 (66.67%)
Anemia 0/6 (0.00%)
Takotsubo cardiomyopathy 1/6 (16.67%)
Pericardial effusion 0/6 (0.00%)
Vertigo 1/6 (16.67%)
Retinal vein occlusion 0/6 (0.00%)
Gastroenteritis 1/6 (16.67%)
Vomiting 1/6 (16.67%)
Diarrhea 0/6 (0.00%)
Death 2/6 (33.33%)
Bile duct dilatation 0/6 (0.00%)
Hepatic hemorrhage 0/6 (0.00%)
Adverse Events 2:
Total: 25/52 (48.08%)
Anemia 1/52 (1.92%)
Takotsubo cardiomyopathy 0/52 (0.00%)
Pericardial effusion 2/52 (3.85%)
Vertigo 0/52 (0.00%)
Retinal vein occlusion 1/52 (1.92%)
Gastroenteritis 0/52 (0.00%)
Vomiting 0/52 (0.00%)
Diarrhea 1/52 (1.92%)
Death 9/52 (17.31%)
Bile duct dilatation 1/52 (1.92%)
Hepatic hemorrhage 1/52 (1.92%) | Entailment |
Patients with ICDs may be eligible for the primary trial. | Exclusion Criteria:
Patients with a Pacemaker or implanted device; | Contradiction |
Asian, white british and white irish women are eligible for the primary trial, as long as they do not have uncontrolled or symptomatic brain metastases. | Inclusion Criteria:
Self-identified Black, African or African American women of 18 years of age with proven diagnosis of advanced adenocarcinoma of the breast (locoregionally recurrent or metastatic disease)
Exclusion Criteria:
Current use of food or drugs known to be potent inhibitors or inducers of CYP3A4
Active uncontrolled or symptomatic brain metastases. Previously treated and clinically stable, as per Investigator's judgment, brain metastases are permitted. | Contradiction |
Cohorts 1 of the primary trial recieves Bevacizumab at a higher frequency and dose than cohort 2. | INTERVENTION 1:
Bevacizumab Plus Paclitaxel
Bevacizumab 10 mg/kg intravenous (i.v.), days 1 and 15, every 4 weeks, Paclitaxel 90 mg/m2, days 1, 8 and 15, every 4 weeks
INTERVENTION 2:
Bevacizumab Plus Capecitabine
Bevacizumab 15 mg/kg i.v., day 1, every 3 weeks, Capecitabine 1000 mg/m² twice-daily, days 1-14, every 3 weeks | Contradiction |
Women of any age can participate in the primary trial and the secondary trial. | Inclusion Criteria:
Women at any age with early stage breast cancer (stage I-II) and American Society of Anesthesiologists (ASA) score of I-II.
Inclusion Criteria:
Age 18 years | Contradiction |
More than 2 cases of Anaphylaxis occurred in either the primary trial or the secondary trial. | Adverse Events 1:
Total: 80/260 (30.77%)
Anaemia * 2/260 (0.77%)
Febrile neutropenia * 0/260 (0.00%)
Neutropenia * 2/260 (0.77%)
Thrombocytopenia * 0/260 (0.00%)
Bundle branch block right * 0/260 (0.00%)
Pericardial effusion * 0/260 (0.00%)
Cardiopulmonary failure * 0/260 (0.00%)
Aplasia * 0/260 (0.00%)
Eye symptom * 1/260 (0.38%)
Abdominal discomfort * 0/260 (0.00%)
Adverse Events 2:
Total: 71/267 (26.59%)
Anaemia * 2/267 (0.75%)
Febrile neutropenia * 1/267 (0.37%)
Neutropenia * 0/267 (0.00%)
Thrombocytopenia * 1/267 (0.37%)
Bundle branch block right * 1/267 (0.37%)
Pericardial effusion * 5/267 (1.87%)
Cardiopulmonary failure * 1/267 (0.37%)
Aplasia * 1/267 (0.37%)
Eye symptom * 0/267 (0.00%)
Abdominal discomfort * 1/267 (0.37%)
Adverse Events 1:
Total: 13/74 (17.57%)
neutropenia 1/74 (1.35%)
left ventricular dysfunction 1/74 (1.35%)
fistula enterovesical 1/74 (1.35%)
constipation and hypokalemia 1/74 (1.35%)
nausea, vomiting and burning abdominal pain 2/74 (2.70%)
Infection 1/74 (1.35%)
febrile neutropenia 3/74 (4.05%)
speech impairment 1/74 (1.35%)
dyspnea, pain 1/74 (1.35%)
hemorrhage/bleeding 2/74 (2.70%) | Contradiction |
Patients must have a life expectancy over a year to participate in the primary trial. | Inclusion Criteria:
Patient who have estimated life expectancy of more than six months | Contradiction |
Molecular Breast Imaging is not applied in either the primary trial or the secondary trial interventions. | INTERVENTION 1:
Active Control Group
Health Education Active Control Group
INTERVENTION 2:
My Surgical Success Treatment Group
My Surgical Success Intervention Group
INTERVENTION 1:
All Study Participants, PA Compression Image Sets
All image sets (30 patient-assisted compression image sets) were evaluated for acceptability of overall clinical image quality by two (2) readers.
INTERVENTION 2:
All Study Participants, TC Compression Image Sets
All image sets (30 TC compression image sets) were evaluated for acceptability of overall clinical image quality by two (2) readers. | Entailment |
Every patient in the primary trial and the secondary trial suffered at least 1 Treatment-emergent adverse event over a span of 2 years. | Outcome Measurement:
Incidence of Treatment-emergent AE's
[Not Specified]
Time frame: 2 years
Results 1:
Arm/Group Title: MM-111 + Herceptin
Arm/Group Description: MM-111 will be combined with Herceptin
MM-111 and Herceptin: For Phase 1: Dose escalation cohorts, MM-111 and Herceptin are administered weekly or bi-weekly via IV
Overall Number of Participants Analyzed: 16
Measure Type: Number
Unit of Measure: participants 16
Outcome Measurement:
Number of Participants With Trastuzumab-Induced Cardiotoxicity After 52 Weeks of Treatment
Reduction in incidence of trastuzumab-induced cardiotoxicity after 52 weeks of treatment as measured by preservation of Left Ventricular Ejection Fraction (LVEF). Number of Patients who experienced a cardiotoxicity.
Time frame: 2 years
Results 1:
Arm/Group Title: Arm I Lisinopril
Arm/Group Description: Patients receive oral lisinopril once daily.
lisinopril: Given orally
Overall Number of Participants Analyzed: 152
Measure Type: Count of Participants
Unit of Measure: Participants 45 29.6% | Contradiction |
All patients in the primary trial must have a bilateral breast mammography prior to study entry. | Inclusion Criteria:
Women 18-75 years old with newly diagnosed breast cancer who are considered candidates for breast conserving surgery (i.e. lumpectomy).
Exclusion Criteria:
Children (<18 years old)
Pregnant or Lactating women
Diabetic patients (Type I or II)
Patients who are scheduled for a sentinel node procedure using radioactive Tc-99m within 24 hours of PEM
Patients who have NOT undergone a standard of care bilateral breast MRI at UC. | Contradiction |
Cohort 1 of the primary trial does not receive any Eribulin Mesylate or Vorinostat, whereas both cohorts in the secondary trial receive some of both. | INTERVENTION 1:
Vorinostat +Trastuzumab
Trastuzumab: 6 mg/kg once on Day 1, infused over 90 minutes, every 3 weeks;
Vorinostat 200 mg of SAHA orally twice a day, daily for 14 days out of a 21-day cycle
INTERVENTION 1:
Cohort 1: Eribulin Mesylate With Filgrastim as Needed
Participants initially received doxorubicin (60 mg/m^2) plus cyclophosphamide (600 mg/m^2) intravenously (IV) on Day 1, of every 14-day cycle for 4 cycles. Eribulin mesylate was administered following the doxorubicin plus cyclophosphamide regimen at a dose of 1.4 mg/m^2 IV over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle for 4 cycles (Cycles 5 to 8). In this Cohort growth factors, subcutaneous pegfilgrastim (6 mg) or filgrastim, could be used with eribulin therapy at the physician's discretion if neutropenia occurred that recovered to Grade 2. | Contradiction |
Patients must have eceptorsestrogen receptor (ER) -, progesterone receptor (PR) - and human epidermal growth factor receptor 2 (HER2) - non metastatic breast cancer, aswell as not having Dysphagia. | Inclusion Criteria:
recurrent or progressive locally advanced, or 'triple negative' metastatic breast cancer
Exclusion Criteria:
Unable to take oral medication | Contradiction |
the primary trial results show that Participants receiving lapatinib 1500 milligrams (mg) orally were twice as likely to achieve DFS at 5 years than placebo patients. | Outcome Measurement:
Number of Participants (Par.) With Any Recurrence of the Initial Disease, Second Primary Cancer, Contralateral Breast Cancer, or Death (Disease-free Survival [DFS])
DFS=interval between the date of randomization and the date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause. The date of the event is the earliest date of the occurrence of any of the following: local recurrence (LR) following mastectomy; LR in ipsilateral breast following lumpectomy; regional recurrence; distant recurrence; contralateral breast cancer, including ductal carcinoma in situ; other second primary cancer (excluding squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, or lobular carcinoma in situ of the breast); death from any cause without a prior event. Par. who started additional anti-cancer adjuvant therapy prior to the recurrence of their disease were to be censored. Par. who did not withdraw from the study and did not experience a specified event or death were to be censored (follow-up ongoing) at the last visit date available at which progression was assessed.
Time frame: From randomization until date of the first occurrence of an objective disease recurrence, a second primary cancer, or death from any cause (assessed up to 6 years; 1 year of treatment, 5 years of follow-up [median of 5.3 years for final analysis])
Results 1:
Arm/Group Title: Lapatinib 1500 mg
Arm/Group Description: Participants received lapatinib 1500 milligrams (mg) orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed: 1571
Measure Type: Number
Unit of Measure: Participants Any recurrence or death: 252
Censored, New Anti-cancer Agent/Radiotherapy: 1
Censored, Follow-up Ended: 1318
Results 2:
Arm/Group Title: Placebo
Arm/Group Description: Participants received matching placebo orally once daily. Treatment was continued for a maximum of 12 months or until disease recurrence or development of a second primary cancer, withdrawal from study treatment due to unacceptable toxicity, or consent withdrawal.
Overall Number of Participants Analyzed: 1576
Measure Type: Number
Unit of Measure: Participants Any recurrence or death: 290
Censored, New Anti-cancer Agent/Radiotherapy: 1
Censored, Follow-up Ended: 1285 | Contradiction |
Patients with Class III obesity cannot be included in the primary trial, but can be entered into the secondary trial, as long as they do not have uncontrolled Hypertension. | Inclusion Criteria:
Body mass index (BMI) of 19 to 40 kg/m^2 , inclusive
Inclusion Criteria:
Patients must have histologically-confirmed adenocarcinoma of the breast with operable or inoperable stage 1c (primary tumor > 1.0 cm), II or III disease.
Measurable disease by physical examinations or diagnostic breast imaging (mammography, ultrasonography or MR).
Pre-treatment core or incisional biopsy. Patients may not have had definitive primary surgery.
Male or female, 18 years of age or older.
ECOG performance status 0 or 1.
Adequate organ function as defined in the protocol.
Exclusion Criteria:
Prior radiation therapy, cytotoxic therapy or systemic therapy for breast cancer. Prior use of tamoxifen or raloxifene as chemoprevention is allowed but must be discontinued prior to study entry.
Metastatic (Stage IV) breast cancer
Patients who have had only a pre-treatment fine needle aspiration (FNA) are excluded.
Current therapeutic treatment on another clinical trial with an investigational agent.
Any of the following within the 6 months prior to starting study treatment: -myocardial infarction -severe/unstable angina -coronary/peripheral artery bypass graft -congestive heart failure -cerebrovascular accident including transient ischemic attack -pulmonary embolus
Ongoing cardiac dysrhythmias of NCI CTCAE grade >=2, atrial fibrillation of any grade, or QTc interval >450 msec for males or >470 msec for females.
Hypertension that cannot be controlled by medications.
Current treatment with therapeutic doses of any anti-coagulant. Prophylactic use of anticoagulants is allowed.
Known human immunodeficiency virus (HIV) infection.
Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test prior to first day of study medication.
Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study. | Entailment |
the primary trial and the secondary trial both report cases of confusion in their patient cohorts. | Adverse Events 1:
Confusion 1/33 (3.03%)
Adverse Events 1:
Confusion 1/11 (9.09%)
Adverse Events 2:
Confusion 0/12 (0.00%) | Entailment |
Only patients capable of understanding english are eligible for the primary trial. | Inclusion Criteria:
Participants must be able to understand English and able to complete assessment forms (all assessment forms are in English). | Entailment |
Intervention 1 for the secondary trial and the primary trial either include no treatment at all, or a placebo. | INTERVENTION 1:
IUS Alone
IUS alone imaging
INTERVENTION 2:
Imagio (IUS+OA)
IUS+OA imaging
INTERVENTION 1:
Placebo
Subjects will be randomly selected to receive saline (placebo), administered to the breast area to cover the intercostal nerves supplying the breast tissue during surgery.
Saline: If randomized to this arm, subjects will receive an intraoperative injection of saline. (2.5 mg/ml)
INTERVENTION 2:
0.25 % Bupivacaine w/ Epinephrine & 4mg Dexamethasone
Subjects will be randomly selected to receive selective block with a local anesthetic solution containing 0.25 % bupivacaine (2.5 mg/ml) with 1:100,000 epinephrine and 4 mg dexamethasone. The injection will be performed in certain locations of the breast area to cover the intercostal nerves supplying the breast tissue.
Subjects will be randomly selected to receive the local anesthetic solution containing 0.25 % bupivacaine (2.5 mg/ml) with 1:100,000 epinephrine and 4 mg dexamethasoneadministered to the breast area to cover the intercostal nerves supplying the breast tissue during surgery.
0.25 % bupivacaine (2.5 mg/ml) w/ 1:100,000 epinephrine & 4 mg dexamethasone: If randomized to this arm, subjects will receive a selective block with a local anesthetic solution containing 0.25 % bupivacaine.
(2.5 mg/ml) with 1:100,000 epinephrine and 4 mg dexamethasone intraoperatively. | Contradiction |
There were twice as many patients with DLT in cohort 2 of the primary trial than in cohort 1. | Outcome Measurement:
Number of Participants With Dose Limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0)
The following events, if considered to be study-treatment-related by the Investigator, were considered a DLT:
Hematologic:
Grade 4 neutropenia lasting 8 days;
Febrile neutropenia Grade 3 or Grade 4; or
Grade 4 thrombocytopenia requiring platelet transfusion, or Grade 3 thrombocytopenia with bleeding
Non-hematologic:
Grade 4 toxicity;
Grade 3 symptomatic hepatic toxicities lasting >48 hours, or Grade 3 asymptomatic hepatic toxicities lasting 7 days; or
Grade 3 non-hematologic, non-hepatic organ toxicity, with exceptions
Other:
Any treatment delays for 14 days due to unresolved toxicity;
Grade 5 treatment-related adverse event (AE);
A dose reduction of study treatment during the DLT evaluation period.
Time frame: Cycle 1 Day 1 through end of Cycle 3 and Cycle 6 Day 1 through end of Cycle 7 (Up to ~150 days from first dose of first combination regimen); Each cycle was 21 days.
Results 1:
Arm/Group Title: Cohort A: KNp / KAC
Arm/Group Description: Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Overall Number of Participants Analyzed: 10
Measure Type: Count of Participants
Unit of Measure: Participants 2 20.0%
Results 2:
Arm/Group Title: Cohort B: KNpCb (Regimen 1) / KAC
Arm/Group Description: Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Overall Number of Participants Analyzed: 10
Measure Type: Count of Participants
Unit of Measure: Participants 4 40.0% | Entailment |
the primary trial does not investigate the effects of its intervention on patient tpCR. | Outcome Measurement:
Progression Free Survival (PFS)
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by investigator review of tumor assessments by RECIST, v1.1 or death on study (<=30 days after the last dose of study treatment regimen) from any cause, whichever occurred first.
Time frame: Baseline up to 30 days after the last dose of study drug administration (Clinical Cut Off Date: 07 June 2016) | Entailment |
There were 6 adverse event categories for cohort 1 of the primary trial which recorded at least three cases. | Adverse Events 1:
Total: 16/56 (28.57%)
Pancytopenia 0/56 (0.00%)
Pericarditis 0/56 (0.00%)
Abdominal pain 1/56 (1.79%)
Anal fissure 1/56 (1.79%)
Ascites 1/56 (1.79%)
Constipation 0/56 (0.00%)
Diarrhoea 1/56 (1.79%)
Nausea 0/56 (0.00%)
Oesophageal pain 0/56 (0.00%)
Vomiting 0/56 (0.00%)
Disease progression 2/56 (3.57%)
Infusion related reaction 1/56 (1.79%)
Pain 0/56 (0.00%) | Contradiction |
Breast breast irradiation is used in some form for both cohorts of the secondary trial, but not at all in the primary trial. | INTERVENTION 1:
Sentinel Lymph Node Biopsy With Radiolabeled Methylene Blue
One arm diagnostic using 1 mCi of 125-I Methylene blue dye to find sentinel lymph nodes
INTERVENTION 1:
Whole Breast Irradiation (WBI)
Conventional whole breast irradiation (WBI)
Whole breast irradiation (WBI): Conventional whole breast irradiation (WBI)
INTERVENTION 2:
Partial Breast Irradiation (APBI)
Accelerated partial breast irradiation (APBI)
Accelerated partial breast irradiation (APBI): Accelerated partial breast irradiation (APBI) using intensity modulated radiotherapy (IMRT) | Entailment |
the primary trial requires participants to have a primary tumor > 5cm in longest dimension. | Inclusion Criteria:
Patients must have completed definitive resection of primary tumor with adequate excision of gross disease. | Contradiction |
Patients in the primary trial receive 5 doses of Azacitidine (Vidaza) every month and 3 doses of Nab-paclitaxel (Abraxane) per month. | INTERVENTION 1:
Phase 1
Azacitidine (Vidaza): 50mg/m2, 75mg/m2 or 100mg/m2 daily for 5 days for each 4-week cycle
Nab-paclitaxel (Abraxane): 100mg/m2 weekly for 3 weeks of each 4-week cycle | Entailment |
The difference in median, maximum and minimum Overall Survival (OS) of Patients between the two cohort of the primary trial was less than one month. | Outcome Measurement:
Overall Survival (OS) of Patients
To compare Overall Survival (OS) of patients who receive 145 mg/m2 NKTR-102 given once every 21 days (q21d) with OS of patients who receive Treatment of Physician's Choice (TPC). Overall survival is defined as the time from the date of randomization to the date of death from any cause. Patients will be followed until their date of death or until final database closure. Patients who are lost-to-follow-up or are alive at the time of analysis will be censored at the time they were last known to be alive or at the date of event cut-off for OS analysis.
Time frame: Within 3 years from study start
Results 1:
Arm/Group Title: NKTR-102
Arm/Group Description: In Group A, NKTR-102 will be administered at a dose level of 145 mg/m2 on a q21d schedule as a 90-minute intravenous (IV) infusion on Day 1 of each treatment cycle.
Overall Number of Participants Analyzed: 92
Median (95% Confidence Interval)
Unit of Measure: months 7.8 (6.1 to 10.2)
Results 2:
Arm/Group Title: Treatment of Physician's Choice (TPC)
Arm/Group Description: In Group B, TPC will be administered per standard of care. Patients randomized to TPC will receive single-agent IV chemotherapy, limited to choice of one of the following 7 agents: eribulin, ixabepilone, vinorelbine, gemcitabine, paclitaxel, docetaxel, or nab-paclitaxel.
Overall Number of Participants Analyzed: 86
Median (95% Confidence Interval)
Unit of Measure: months 7.5 (5.8 to 10.4) | Entailment |
There are four types of adverse events in the primary trial, for which one occurence is recorded. | Adverse Events 1:
Total: 47/254 (18.50%)
Anaemia 1/254 (0.39%)
Febrile neutropenia 1/254 (0.39%)
Lymphadenopathy 1/254 (0.39%)
Acute myocardial infarction 1/254 (0.39%)
Angina pectoris 0/254 (0.00%)
Angina unstable 0/254 (0.00%)
Bundle branch block left 0/254 (0.00%)
Cardiac failure 4/254 (1.57%)
Coronary artery disease 0/254 (0.00%)
Coronary artery stenosis 1/254 (0.39%) | Contradiction |
1 patient in the primary trial was affected by Sepsis, and several were affected in the secondary trial. | Adverse Events 1:
Total: 17/40 (42.50%)
Anaemia 2/40 (5.00%)
Febrile Neutropenia 3/40 (7.50%)
Neutropenia 2/40 (5.00%)
Thrombocytopenia 5/40 (12.50%)
Pericardial Effusion 1/40 (2.50%)
Abdominal Pain Lower 1/40 (2.50%)
Disease Progression 6/40 (15.00%)
Fatigue 1/40 (2.50%)
Pyrexia 3/40 (7.50%)
Septic Shock 1/40 (2.50%)
Streptococcal Infection 1/40 (2.50%)
Adverse Events 1:
Total: 1/3 (33.33%)
Pain 0/3 (0.00%)
Cellulitis 0/3 (0.00%)
Influenza 0/3 (0.00%)
Osteomyelitis 0/3 (0.00%)
Pneumonia 0/3 (0.00%)
Humerus Fracture 0/3 (0.00%)
Brain Oedema 0/3 (0.00%)
Cerebral Haemorrhage 0/3 (0.00%)
Convulsion 0/3 (0.00%)
Dysarthria 0/3 (0.00%)
Hepatic Encephalopathy 0/3 (0.00%)
Confusional State 0/3 (0.00%)
Dyspnoea 1/3 (33.33%)
Adverse Events 2:
Total: 1/1 (100.00%)
Pain 0/1 (0.00%)
Cellulitis 0/1 (0.00%)
Influenza 0/1 (0.00%)
Osteomyelitis 0/1 (0.00%)
Pneumonia 0/1 (0.00%)
Humerus Fracture 0/1 (0.00%)
Brain Oedema 0/1 (0.00%)
Cerebral Haemorrhage 0/1 (0.00%)
Convulsion 0/1 (0.00%)
Dysarthria 0/1 (0.00%)
Hepatic Encephalopathy 0/1 (0.00%)
Confusional State 0/1 (0.00%)
Dyspnoea 0/1 (0.00%) | Contradiction |
Patients in the primary trial and the secondary trial did not suffer from any of the same adverse events. | Adverse Events 1:
Total: 5/261 (1.92%)
Cholecystitis chronic 1/261 (0.38%)
Post procedural bile leak 1/261 (0.38%)
Spinal column stenosis 1/261 (0.38%)
Depression 1/261 (0.38%)
Mania 1/261 (0.38%)
Pulmonary embolism 1/261 (0.38%)
Adverse Events 1:
Total: 12/63 (19.05%)
Febrile neutropenia * [1]4/63 (6.35%)
Congestive heart failure * [2]1/63 (1.59%)
Cardiac-ischemia/infarction * 1/63 (1.59%)
Vomiting * [1]1/63 (1.59%)
Acute Pharyngitis * 1/63 (1.59%)
Infection * 3/63 (4.76%)
Neutrophil count decreased * [1]1/63 (1.59%)
Pneumonitis/pulmonary infiltrates * [3]1/63 (1.59%) | Entailment |
The duration of treatment in the primary trial is half as long as in the secondary trial, but twice as frequent. | INTERVENTION 1:
Letrozole
Letrozole, 2.5 mg daily for six months
INTERVENTION 1:
Celecoxib
Randomized to receive celecoxib daily for 12 months
INTERVENTION 2:
Placebo
Randomized to receive placebo daily for 12 months | Contradiction |
The longest Time to Disease Progression the primary trial was over 21 days in the Docetaxel Plus Capecitabine group. | Outcome Measurement:
Time to Disease Progression (Initial Treatment)
Time to disease progression (TTDP) at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first. TTDP censored at earliest of: 1) date of death not due to disease; or 2) date of last contact for participants alive without disease progression; or 3) start date of other anti-tumor therapy; or 4) first dose date of crossover treatment.
Time frame: Randomization date to the earliest date of first documented disease progression date or the date of death if the participant died due to study disease (up to 82 months)
Results 1:
Arm/Group Title: Gemcitabine Plus Docetaxel
Arm/Group Description: gemcitabine 1000 milligrams per meter squared (mg/m2) intravenous, days 1 and 8 every 21 days plus docetaxel 75 mg/m2, intravenous, day 1 every 21 days.
Treatment continues until progression of disease at which time crossover treatment begins.
Overall Number of Participants Analyzed: 239
Median (95% Confidence Interval)
Unit of Measure: months 9.28 (7.73 to 10.79)
Results 2:
Arm/Group Title: Docetaxel Plus Capecitabine
Arm/Group Description: docetaxel 75 mg/m2, intravenous, day 1 every 21 days plus capecitabine 1000 mg/m2, by mouth twice a day, days 1-14 every 21 days. Treatment continues until progression of disease, at which time crossover treatment begins.
Overall Number of Participants Analyzed: 236
Median (95% Confidence Interval)
Unit of Measure: months 8.88 (7.37 to 11.05) | Contradiction |
the primary trial results indicate that CoQ10 reduces the PFS of breast cancer patients compared to a placebo by about 8% | Outcome Measurement:
Effects of Coenzyme Q10 on Fatigue (as Measured by POMS-F) 24 Weeks Following Randomization
POMS-F is the Profile of Mood States - fatigue scale. It ranges from 0 to 28; higher values indicate greater fatigue.
Time frame: 24 weeks
Results 1:
Arm/Group Title: Arm 1 - CoQ10 & Vitamin E
Arm/Group Description: CoQ10 100mg capsule combined with Vitamin E 100 IU taken orally three times per day.
Overall Number of Participants Analyzed: 122
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale 6.96 (0.71)
Results 2:
Arm/Group Title: Arm 2 - Placebo & Vitamin E
Arm/Group Description: Placebo-Vitamin E 100 mg/day in 3 doses
Overall Number of Participants Analyzed: 114
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale 8.33 (0.79) | Contradiction |
At least one type of respiratory illness was observed in patients from both the primary trial and the secondary trial. | Adverse Events 1:
Parainfluenzae virus infection 1/39 (2.56%)
Adverse Events 1:
PNEUMONIA 1/70 (1.43%) | Entailment |
Patients may be forced to take part in the secondary trial and the primary trial, even against their consent, as long as it is in their best interests. | Inclusion Criteria:
ability and willingness to sign written consent
Inclusion Criteria:
Written informed consent | Contradiction |
The most common adverse event in the primary trial was Febrile neutropenia (14.29%), whereas in the secondary trial it was a decrease in Ejection fraction (4.95%). | Adverse Events 1:
Total: 7/7 (100.00%)
Febrile neutropenia 3/7 (42.86%)
Cardiac failure 1/7 (14.29%)
Neutrophil count decreased 1/7 (14.29%)
Muscular weakness 1/7 (14.29%)
Epistaxis 1/7 (14.29%)
Interstitial lung disease 1/7 (14.29%)
Pleural effusion 2/7 (28.57%)
Adverse Events 1:
Total: 8/101 (7.92%)
Vertigo * 1/101 (0.99%)
Infected lymphocele * 1/101 (0.99%)
Ejection fraction decreased * 5/101 (4.95%)
Lymphoedema * 1/101 (0.99%) | Contradiction |
2 patients in the primary trial suffer from DVT, 0 in the secondary trial. | Deep vein thrombosis 1/28 (3.57%)
Adverse Events 1:
Total: 1/24 (4.17%)
Pericardial effusion *1/24 (4.17%)
Other cardiac disorder *0/24 (0.00%)
Ejection fraction decrease *0/24 (0.00%)
Hypertension *0/24 (0.00%)
Salivary gland infection *0/24 (0.00%)
Pleural effusion *0/24 (0.00%)
Adverse Events 2:
Total: 6/30 (20.00%)
Pericardial effusion *1/30 (3.33%)
Other cardiac disorder *1/30 (3.33%)
Ejection fraction decrease *1/30 (3.33%)
Hypertension *1/30 (3.33%)
Salivary gland infection *1/30 (3.33%)
Pleural effusion *2/30 (6.67%) | Contradiction |
Intervention 2 of the primary trial resulted in a lower percentage change in tumor diameter than intervention 1. | Outcome Measurement:
Percent Change (Between Baseline and Month 12) in Mammographic Density by the Boyd Method Compared Between Arms
To evaluate change in mammographic density using the Boyd method after one year of vitamin D supplementation compared to placebo in premenopausal women. The percent change in breast density will be reported here.
Time frame: 12 months
Results 1:
Arm/Group Title: Placebo
Arm/Group Description: Patients receive oral placebo once daily for 12 months.
Overall Number of Participants Analyzed: 46
Mean (Standard Deviation)
Unit of Measure: percent change -3.4 (7.1)
Results 2:
Arm/Group Title: Vitamin D
Arm/Group Description: Patients receive oral vitamin D (2000 IU) once daily for 12 months.
Overall Number of Participants Analyzed: 40
Mean (Standard Deviation)
Unit of Measure: percent change -1.4 (11.9) | Contradiction |
All participants in the primary trial had a Central Nervous System (CNS) Progression Free Survival (PFS) >= 16 weeks. | Outcome Measurement:
Percent of Participants With Central Nervous System (CNS) Progression Free Survival (PFS)
The study team will assess the percent of participants without CNS progression at 3 months. The study team will generate a Kaplan- Meier curve of CNS PFS and estimate the PFS and 95% confidence interval (CI) of the PFS. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.
Time frame: At 12 weeks
Results 1:
Arm/Group Title: Eribulin Mesylate
Arm/Group Description: The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate
Eribulin Mesylate: Most subjects will begin eribulin mesylate at 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle.
MRI: An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate
Pre-Medication: Zofran: Zofran at 8mg orally. Given at the discretion of the treating physician
Pre-Medication: Decadron: decadron at 8mg orally. Given at the discretion of the treating physician
Overall Number of Participants Analyzed: 9
Measure Type: Number
Unit of Measure: percentage of participants 88.9 (51 to 99.7) | Contradiction |
the secondary trial and the primary trial are evaluating interventions associated with breast reconstruction for patients that have had mastectomies. | INTERVENTION 1:
Nipple Reconstruction Cylinder
Nipple reconstruction: Biodesign® Nipple Reconstruction Cylinder
INTERVENTION 1:
Arm 1: BREASTChoice (Decision Tool)
Investigators recruited patients scheduled for a plastic/reconstruction consult. Investigators identified patients who completed a mastectomy, or were scheduled for one, and considering reconstruction, but didn't have an appointment with a plastic/reconstructive surgeon. A study team member called the patient to determine their interest and offered for them to come to their scheduled appointment 30 minutes early to meet a coordinator or offered them the option to complete pre-appointment procedures at home. Patients randomized using computer random assignment. If the patient didn't have an appointment, she scheduled a convenient time to complete study procedures with research staff. Patients interacted with the decision tool. They were asked to answer a survey. After the appointment, the team collected information consult duration, decision process quality, and measures of shared decision making. Patient participation was approximately 30 minutes. | Entailment |
Both cohorts of the primary trial in a negative (mean) Percent Change From Baseline of Creatinine-adjusted Urinary N-telopeptide (uNTx/Cr). | Outcome Measurement:
Percent Change From Baseline to Week 13 in Creatinine-adjusted Urinary N-telopeptide (uNTx/Cr)
Percent change from Baseline to Week 13 in Urinary N-telopeptide corrected by creatinine (uNTx/Cr) calculated using ((Week 13 value - Baseline value) / Baseline value ) x 100.
Time frame: Baseline and Week 13
Results 1:
Arm/Group Title: Bisphosphonate IV Q4W
Arm/Group Description: Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
Overall Number of Participants Analyzed: 38
Mean (Standard Deviation)
Unit of Measure: Percent change -10.19 (208.84)
Results 2:
Arm/Group Title: Denosumab 30 mg Q4W
Arm/Group Description: Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
Overall Number of Participants Analyzed: 40
Mean (Standard Deviation)
Unit of Measure: Percent change -52.87 (95.14) | Entailment |
Breast implants and Diffuse microcalcifications will not disqualify a patient from entry to the primary trial. | Inclusion Criteria:
Female, 18-100 years old
Not pregnant or breastfeeding
Pre-study radiologic documentation of:
size 5 cm
unicentric, unilateral
suspicious mass or calcification
BIRADS classification IV
location of abnormality > 1 cm from skin
Ductal or Infiltrating Ductal Carcinoma
Grade I-III on final pathology
Good general health
Zubrod Performance Status of 0,1, or 2
No previous chemotherapy
No palpable axillary or supraclavicular lymph nodes
If prior non-breast malignancy, must have > 5 year disease-free survival
Exclusion Criteria:
Patient < 18 y/o or > 100 y/o
Pregnant or breastfeeding
Male
Breast implants
Multicentric disease or bilateral disease
Lesions > 5 cm in diameter
Lesions < 1.0 cm from the skin
Previous prior radiation to the breast
Need for mastectomy
Diffuse microcalcifications (as determined by the Investigator) | Contradiction |
Cohort 2 subjects of the primary trial receive 3.25 mg of vaginal DHEA gel QD more than cohort 1 subjects, of the two cohorts in the secondary trial only the cohort without pain recieves Duloxetine 30 mg daily. | INTERVENTION 1:
Arm I Low Dose DHEA
Participants apply a low dose (3.25 mg) of vaginal prasterone (dehydroepiandrosterone [DHEA]) gel once daily (QD), at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.
INTERVENTION 2:
Arm II High Dose DHEA
Participants apply a high dose (6.5 mg) of vaginal DHEA gel QD, at bed time, for 12 weeks. Treatment continues until unacceptable adverse events or patient refusal to continue participation on the study.
INTERVENTION 1:
Arm 1 (Patients With Pain)
Duloxetine 30 mg daily x 1 week, then 60 mg daily x 4 weeks, then 30 mg daily x 2 weeks.
Duloxetine: Subjects will receive 30 mg duloxetine orally for 7 days, then 60 mg duloxetine orally for 28 days, then 30 mg duloxetine orally x 14 days.
INTERVENTION 2:
Arm 2 (Patients Without Pain -- Control)
Patient reported pain and symptoms assessment for comparison at baseline. | Contradiction |
Patients must have a confirmed pregnancy by positive Hcg test, if they are to take part in the primary trial. | Postmenopausal status defined as cessation of menses for >1 year or FSH > 20 mIU/mL (within the past month) | Contradiction |
There was less than a 5% difference in the Percentage of Participants With Objective Response in the GTx-024 9 mg and GTx-024 18 mg group in the primary trial. | Outcome Measurement:
Clinical Benefit Rate, in Centrally Confirmed Androgen Receptor (AR)+ Subjects
To estimate the clinical benefit rate (defined as complete response, partial response, or stable disease) according to RECIST 1.1, in subjects with estrogen receptor positive/androgen receptor positive (ER+/AR+) BC who have centrally confirmed AR+ status. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR; Clinical Benefit Rate (CBR)= CR + PR + SD.
Time frame: 24 weeks
Results 1:
Arm/Group Title: GTx-024 9 mg
Arm/Group Description: Drug: GTx-024 GTx-024 softgel capsules will be administered once daily to a total dose of 9 mg
GTx-024: To determine whether either or both doses result in an acceptable clinical benefit rate.
Overall Number of Participants Analyzed: 50
Measure Type: Number
Unit of Measure: participants 16
Results 2:
Arm/Group Title: GTx-024 18 mg
Arm/Group Description: Drug: GTx-024 GTx-024 softgel capsules will be administered once daily to a total dose of 18 mg
GTx-024: To determine whether either or both doses result in an acceptable clinical benefit rate.
Overall Number of Participants Analyzed: 52
Measure Type: Number
Unit of Measure: participants 15 | Contradiction |
the primary trial records a total of 7 different types of infections. | Adverse Events 1:
Total: 22/123 (17.89%)
Cardiac Ischemia/Infarction [1]1/123 (0.81%)
Pain - Chest 2/123 (1.63%)
Dehydration 2/123 (1.63%)
Death [2]1/123 (0.81%)
Weakness 1/123 (0.81%)
Pain - Liver 1/123 (0.81%)
Infection - Skin [3]3/123 (2.44%)
Infection - Gastrointestinal [4]1/123 (0.81%)
Infection - Vein [5]2/123 (1.63%)
Infection - Pneumonia 1/123 (0.81%) | Contradiction |
There are no details concerning the duration or frequency of administration in the intervention sections of the primary trial and the secondary trial | INTERVENTION 1:
All Study Participants: Patient Assisted Compression
All subjects will undergo standard of care imaging on one breast. The other breast will be imaged using Patient-Assisted Compression (PAC), followed by Technologist-controlled (TC) Compression.
Patient-Assisted Compression (PAC): The technologist will properly position the breast and apply minimum compression. The subject will be instructed to apply compression as the technologist ensures the breast tissue is in appropriate position and tautness. The technologist will then guide the subject to achieve appropriate compression level, sufficient but not excessive, and the image will be acquired. This will be done for both standard views CC & MLO.
INTERVENTION 2:
All Study Participants: Technologist Compression
All subjects will undergo standard of care imaging on one breast. The other breast will be imaged using Patient-Assisted Compression (PAC), followed by Technologist-controlled (TC) Compression.
Technologist-Controlled (TC) Compression: TC compression will be conducted per standard of care practices at the site.
INTERVENTION 1:
FFDM Plus DBT
Breast Images with FFDM and DBT FFDM Plus DBT: FujiFilm Aspire Cristalle System.
This endpoint will be evaluated qualitatively. The Pass Criteria require adequate performance in non-cancer cases (recall rate) and in cancer cases (detection rate).
INTERVENTION 2:
Full-Field Digital Mammography (FFDM)
Breast Images with FFDM alone FFDM: FujiFilm Aspire Cristalle System.
This endpoint will be evaluated qualitatively. The Pass Criteria require adequate performance in non-cancer cases (recall rate) and in cancer cases (detection rate). | Entailment |
the primary trial and the secondary trial do not use any of the same drugs in their interventions. | INTERVENTION 1:
Treatment Schedule (Weekly)
Arm C, Docetaxel and Gemcitabine (Weekly):
Docetaxel: 30 mg/m², 30-60 min IV infusion on Days 1, 8, and 15 to be given 30 minutes prior to Gemcitabine, repeated every 28 days (weekly) for 10 cycles for CRs or PRs; 6 cycles for SD; or until PD.
Gemcitabine: 800 mg/m², 30 min IV infusion on Days 1, 8, and 15 repeated every 28 days for 10 cycles for CRs or PRs; 6 cycles for SD; or until PD.
Arm D, Paclitaxel and Gemcitabine (Weekly):
Paclitaxel: 80 mg/m², IV infusion over approximately 1 hour, Days 1, 8, and 15, followed by Gemcitabine, repeated every 28 days (weekly) for 10 cycles for CRs or PRs; 6 cycles for SD; or until PD.
Gemcitabine: 800 mg/m², 30 min IV infusion on Days 1, 8, and 15 repeated every 28 days for 10 cycles for CRs or PRs; 6 cycles for SD; or until PD.
INTERVENTION 2:
Treatment Schedule (3 Weekly)
Arm A, Docetaxel and Gemcitabine (3 Weekly):
Docetaxel: 75 mg/m², 60 min IV infusion on Day 1 only, to be given 30 min prior to Gemcitabine, repeated every 21 days (tri-weekly) for 10 cycles for CRs or PRs; 6 cycles for SD; or until PD.
Gemcitabine: 1000 mg/m², 30 min IV infusion on Days 1 and 8, repeated every 21 days for 10 cycles for CRs or PRs; 6 cycles for SD; or until PD.
Arm B, Paclitaxel and Gemcitabine (3 Weekly):
Paclitaxel: 175 mg/m², IV infusion over approximately 3 hours followed by Gemcitabine, repeated every 21 days (tri-weekly) for 10 cycles for CRs or PRs; 6 cycles for SD; or until PD.
Gemcitabine: 1250 mg/m², 30 min IV infusion on Days 1 and 8, repeated every 21 days for 10 cycles for CRs or PRs; 6 cycles for SD; or until PD.
INTERVENTION 1:
Treatment (Enzyme Inhibitor Therapy, AI Sensitization Therapy)
Patients receive vorinostat PO QD for 2 weeks followed by AI therapy comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
vorinostat: Given PO
laboratory biomarker analysis: Correlative studies
biopsy: Optional correlative studies
F-18 16 alpha-fluoroestradiol: Correlative studies
positron emission tomography: Correlative studies
anastrozole: Given PO
letrozole: Given PO
exemestane: Given PO
gene expression analysis: Correlative studies | Entailment |
In total Over 85% patient in the primary trial achieve Recurrence-free Survival after 3 years. | Outcome Measurement:
Recurrence-free Survival
2 years for the primary analysis + 3 additional years for secondary analysis (From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 5 years)
Time frame: 5 years
Results 1:
Arm/Group Title: Ketorolac 30 mg
Arm/Group Description: Active drug to be compared with placebo
Ketorolac 30 mg IV
Overall Number of Participants Analyzed: 96
Measure Type: Count of Participants
Unit of Measure: Participants 80 83.3%
Results 2:
Arm/Group Title: NaCl 0.9% 3mL
Arm/Group Description: Ketorolac 30 mg IV
Overall Number of Participants Analyzed: 107
Measure Type: Count of Participants
Unit of Measure: Participants 96 89.7% | Contradiction |
Throughout both the secondary trial and the primary trial there was only one case of sudden and unexpected death, in cohort 1 of the secondary trial. | Adverse Events 1:
Total: 17/145 (11.72%)
ANAEMIA 0/145 (0.00%)
LEUKOPENIA 2/145 (1.38%)
NEUTROPENIA 1/145 (0.69%)
LEUKOCYTOSIS 1/145 (0.69%)
THROMBOCYTOPENIA 1/145 (0.69%)
FEBRILE NEUTROPENIA 1/145 (0.69%)
THROMBOTIC THROMBOCYTOPENIC PURPURA 0/145 (0.00%)
DISSEMINATED INTRAVASCULAR COAGULATION 0/145 (0.00%)
CARDIAC FAILURE 1/145 (0.69%)
ATRIAL FIBRILLATION 1/145 (0.69%)
Adverse Events 2:
Total: 11/144 (7.64%)
ANAEMIA 1/144 (0.69%)
LEUKOPENIA 0/144 (0.00%)
NEUTROPENIA 0/144 (0.00%)
LEUKOCYTOSIS 0/144 (0.00%)
THROMBOCYTOPENIA 0/144 (0.00%)
FEBRILE NEUTROPENIA 1/144 (0.69%)
THROMBOTIC THROMBOCYTOPENIC PURPURA 1/144 (0.69%)
DISSEMINATED INTRAVASCULAR COAGULATION 1/144 (0.69%)
CARDIAC FAILURE 0/144 (0.00%)
ATRIAL FIBRILLATION 0/144 (0.00%)
Adverse Events 1:
Total: 22/79 (27.85%)
Anaemia 0/79 (0.00%)
Right ventricular dysfunction 1/79 (1.27%)
Diarrhoea 1/79 (1.27%)
Vomiting 2/79 (2.53%)
Abdominal pain 0/79 (0.00%)
Colonic obstruction 0/79 (0.00%)
Dysphagia 1/79 (1.27%)
Nausea 1/79 (1.27%)
Mucosal inflammation 1/79 (1.27%)
Performance status decreased 1/79 (1.27%)
Sudden death 1/79 (1.27%)
Adverse Events 2:
Total: 13/76 (17.11%)
Anaemia 1/76 (1.32%)
Right ventricular dysfunction 0/76 (0.00%)
Diarrhoea 0/76 (0.00%)
Vomiting 2/76 (2.63%)
Abdominal pain 1/76 (1.32%)
Colonic obstruction 1/76 (1.32%)
Dysphagia 0/76 (0.00%)
Nausea 1/76 (1.32%)
Mucosal inflammation 0/76 (0.00%)
Performance status decreased 0/76 (0.00%)
Sudden death 0/76 (0.00%) | Entailment |
For all adverse event types in the primary trial, at least one case was recorded. | Adverse Events 1:
Total: 6/8 (75.00%)
Thrombocytopenia 1/8 (12.50%)
Hypertension 1/8 (12.50%)
Hepatotoxicity 3/8 (37.50%)
Pancreatectomy * 1/8 (12.50%) | Entailment |