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Both cohorts the primary trial apply the topical intervention for approximately every 4-6 hours every day for a week of the study. | INTERVENTION 1:
Arm I (Curcumin-based Gel)
Patients apply curcumin-based gel topically TID approximately every 4-6 hours beginning on the first day of radiation therapy and continuing until 1 week after completion of radiation therapy.
Curcumin-based Gel: Applied topically
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies
INTERVENTION 2:
Arm II (HPR Plus)
Patients apply HPR Plus™ topically TID approximately every 4-6 hours beginning on the first day of radiation therapy and continuing until 1 week after completion of radiation therapy.
Dermatologic Complications Management: Apply HPR Plus topically
Laboratory Biomarker Analysis: Correlative studies
Questionnaire Administration: Ancillary studies | Entailment |
the primary trial recorded half as many patients vomiting as the secondary trial. | Adverse Events 1:
Nausea 1/20 (5.00%)
Adverse Events 1:
Nausea/vomiting 4/39 (10.26%) | Contradiction |
Cohort 2 of the primary trial recieves Doxorubicin only during cycles 1-4, and then Doxorubicin, cyclophosphamide, Herceptin and docetaxel during Cycle 5 of the study. | INTERVENTION 2:
AC Followed by Docetaxel + Herceptin (AC→TH)
Doxorubicin 60 mg/m² IV bolus injection in combination with cyclophosphamide 600 mg/m² IV bolus Injection on Day 1 of every 3 weeks for 4 cycles. Herceptin 4 mg/kg IV infusion on Day 1 of Cycle 5, followed by Herceptin 2 mg/kg by IV infusion weekly starting from Day 8; and docetaxel 100 mg/m² IV infusion on Day 2 of Cycle 5, then on Day 1 of every 3 weeks for all subsequent cycles ( total 4 cycles). After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose. | Contradiction |
Only Chinese women with stage 4 or Unresectable, locally recurrent cancer breast cancer are eligible for the primary trial. | Inclusion Criteria:
Female patients of Chinese origin with histologically or cytologically proven diagnosis of breast cancer.
Unresectable, locally recurrent breast cancer or stage IV disease. | Entailment |
Participants of cohort 1 in the primary trial received more Dasatinib and Paclitaxel than those in cohort 2. | INTERVENTION 1:
Phase I: Dasatinib 100mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2
Cohort 1: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 100mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days.
INTERVENTION 2:
Phase I: Dasatinib 140mg/Trastuzumab 2mg/kg/Paclitaxel 80mg/m2
Cohort 2: Eligible patients were enrolled and treated with 4-week cycles of trastuzumab 2 mg/kg IV weekly (following a loading dose of 4 mg/kg in cycle 1) and paclitaxel 80 mg/m2 weekly x 3 weeks followed by a rest period of 7 days. Dasatinib 140mg was administered orally once daily (QD). Treatment was repeated on Day 1 of a 28-day cycle until radiographic or symptomatic progression or unacceptable toxicity occured. Only in the phase I, the first cycle lasted 38 days. | Contradiction |
the primary trial recorded 23 adverse events. | Adverse Events 1:
Total: 0/23 (0.00%) | Contradiction |
There were no adverse event in the primary trial which affected more than 10% of a particular patient cohort. | Adverse Events 1:
Febrile neutropenia 30/280 (10.71%) | Contradiction |
Patients with pure ductal carcinoma in situ (DCIS) or Melanoma are eligible for both the secondary trial and the primary trial, and are able to participate in these trials alongside other drug trials, up to a maximum of 3. | Inclusion Criteria:
The patient is currently not participating in another investigational drug study.
Patients with pure ductal carcinoma in situ (DCIS) or non-invasive carcinoma if lymph node biopsy is part of the surgical plan.
Inclusion Criteria:
Ductal or Infiltrating Ductal Carcinoma | Contradiction |
Patients must have histologically or cytologically confirmed PR+ invasive breast cancer, with Primary tumor > 2 cm in diameter TO PARTICIPATE in the primary trial. | Inclusion Criteria:
Patients must have histologically or cytologically confirmed primary invasive breast cancer
Primary tumor is larger than 2 cm in diameter (T2) as measured by caliper or ultrasound
Overexpression and/or amplification of HER2 is confirmed by immunohistochemistry (IHC) 3+ or fluorescence in situ hybridization (FISH) + when IHC 2+ | Contradiction |
There was 16.67% more cases of hemorrhaging in the primary trial than in the secondary trial. | Adverse Events 1:
Total: 7/15 (46.67%)
Cardiac arrest * 1/15 (6.67%)
Chest pain - cardiac * 1/15 (6.67%)
Diarrhea * 1/15 (6.67%)
Duodenal hemorrhage * 1/15 (6.67%)
Fatigue * 1/15 (6.67%)
Fever * 1/15 (6.67%)
Sudden death NOS * 1/15 (6.67%)
Sepsis * 1/15 (6.67%)
Skin infection * 1/15 (6.67%)
Neutrophil count decreased * 1/15 (6.67%)
Platelet count decreased * 1/15 (6.67%)
Adverse Events 1:
Total: 69/258 (26.74%)
Anaemia 3/258 (1.16%)
Febrile neutropenia 13/258 (5.04%)
Neutropenia 5/258 (1.94%)
Thrombocytopenia 1/258 (0.39%)
Atrial fibrillation 0/258 (0.00%)
Mitral valve incompetence 1/258 (0.39%)
Pericardial effusion 0/258 (0.00%)
Sinus tachycardia 0/258 (0.00%)
Abdominal pain 3/258 (1.16%)
Abdominal pain upper 1/258 (0.39%)
Colitis 1/258 (0.39%)
Adverse Events 2:
Total: 64/224 (28.57%)
Anaemia 2/224 (0.89%)
Febrile neutropenia 4/224 (1.79%)
Neutropenia 1/224 (0.45%)
Thrombocytopenia 0/224 (0.00%)
Atrial fibrillation 1/224 (0.45%)
Mitral valve incompetence 0/224 (0.00%)
Pericardial effusion 2/224 (0.89%)
Sinus tachycardia 1/224 (0.45%)
Abdominal pain 3/224 (1.34%)
Abdominal pain upper 0/224 (0.00%)
Colitis 0/224 (0.00%) | Contradiction |
In the primary trial, Dasatinib, 70 mg, Twice Daily results in a better median PFS than Dasatinib, 100 mg, Daily. The opposite was true in the secondary trial. | Outcome Measurement:
Progression-free Survival
RECIST progression defined as 20% increase in the sum of longest diameters of target measurable lesions over the smallest sum observed, unequivocal progression of non-measurable disease, the appearance of any new lesion/site, death due to disease without prior documentation of progression and without symptomatic deterioration, development of one or more new bone lesions from baseline, or symptomatic deterioration related to disease progression. Time from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at last date of contact.
Time frame: Up to 2 years
Results 1:
Arm/Group Title: Dasatinib, 100 mg, Daily
Arm/Group Description: Dasatinib, 100 mg PO daily until progression of disease
Overall Number of Participants Analyzed: 41
Median (95% Confidence Interval)
Unit of Measure: weeks 10.3 (8.4 to 16.7)
Results 2:
Arm/Group Title: Dasatinib, 70 mg, Twice Daily
Arm/Group Description: Dasatinib, 70 mg PO twice daily until progression of disease
Overall Number of Participants Analyzed: 38
Median (95% Confidence Interval)
Unit of Measure: weeks 15.3 (8.7 to 20.1)
Outcome Measurement:
Number of Patients With Objective Treatment Response (Complete or Partial) in the CNS
Imaging was performed at 8-week intervals to assess response to treatment. Patients with known or suspected leptomeningeal disease were deemed to have a complete response if CSF cytology converted to negative (if positive at baseline) and all meningeal enhancement or nodularity of brain and/or spine MRI resolved. A modified RECIST 1.0 criteria was used to assess CNS response for patients with new or progressing brain metastases. In this modified RECIST criteria, CNS lesions <1cm were not considered measurable, but were considered evaluable for response and progression. Progressive disease for patients with lesions <1 cm was defined as follows: growth of a lesion from less than or equal to 5 mm to greater than or equal to 10mm; or, growth of a 6-9 mm lesion by at least 5 mm in the case of non-target parenchymal brain metastases.
Time frame: Baseline scan prior to study entry was performed within 14 days of cycle 1 day 1, then every 8 weeks from then until disease progression or up to 2 years
Results 1:
Arm/Group Title: Irinotecan and Temozolomide
Arm/Group Description: irinotecan hydrochloride administered intravenously (IV) at a starting dose of 125 mg/m2 on days 1 and 15 of a 28 day cycle
temozolomide orally for seven days at a starting dose of 100 mg/m2 on days 1-7 and days 15-21 of a 28 day cycle
Overall Number of Participants Analyzed: 30
Measure Type: Count of Participants
Unit of Measure: Participants 2 6.7% | Contradiction |
Between both of the patient cohorst of the primary trial and the secondary trial there was only a single patient who suffered heart failure. | 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%) | Contradiction |
At least one participant in the primary trial receiving an oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusions of Vinorelbine 25 mg/meter^2 (meter=m) had a PFS over 9 months. | Outcome Measurement:
Progression-free Survival (PFS)
PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by investigator according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment.
Only data collected until the cut-off date for RECIST 1.1 based endpoints (08Jun2013) were considered.
Progression of disease was determined if at least 1 of the following criteria applied:
At least a 20% increase in the sum of the diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the treatment started, together with an absolute increase in the SoD of at least 5 mm
Appearance of 1 or more new lesions
Unequivocal progression of existing non-target lesions
Time frame: From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months
Results 1:
Arm/Group Title: Afatinib + Vinorelbine (AV)
Arm/Group Description: Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.
Overall Number of Participants Analyzed: 339
Median (Inter-Quartile Range)
Unit of Measure: Months 5.49 (3.55 to 9.07) | Entailment |
the primary trial and the secondary trial do not have any overlapping inclusion or exclusion criteria. | Inclusion Criteria:
Previous participation in study 971-ONC-0028-080.
Exclusion Criteria:
Subjects who had not previously participated in study 971-ONC-0028-080.
DISEASE CHARACTERISTICS:
Diagnosis of breast cancer at high risk for recurrence, defined by one of the following:
Stage IV that is free of all known disease after eradication by surgery, radiotherapy, or chemotherapy
May or may not have elevated CA 15-3 or CEA levels
Stage I, II, or III previously treated with adjuvant chemotherapy and clinically free of identifiable disease, but have rising CA 15-3 or CEA levels
Rising CA 15-3 and CEA defined as a prior normal level increased on 2 consecutive occasions at least 2 weeks apart
For patients with a significant history of smoking who have a chronically elevated CEA (less than 15), CEA must be increased at least 1.5 times the uppermost chronic value on 2 consecutive occasions at least 2 weeks apart
Stage III and completed adjuvant therapy no more than 24 months ago
Recurrence in the ipsilateral axilla after lumpectomy and/or axillary dissection or modified radical mastectomy
Recurrence in the ipsilateral breast after lumpectomy and/or axillary dissection
Stage II with at least 4 positive axillary nodes and completed adjuvant therapy no more than 24 months ago
Stage IV that is stable on hormonal therapy
Hormone receptor status:
Not specified
PATIENT CHARACTERISTICS:
Age:
18 and over
Sex:
Male or female
Menopausal status:
Not specified
Performance status:
Karnofsky 80-100%
Life expectancy:
Not specified
Hematopoietic:
Lymphocyte count at least 500/mm^3
WBC at least 3,000/mm^3
Hepatic:
AST no greater than 1.5 times upper limit of normal (ULN)
Alkaline phosphatase no greater than 1.5 times ULN
Renal:
Creatinine no greater than 1.5 times ULN
Cardiovascular:
No clinically significant New York Heart Association class III or IV cardiac disease
Other:
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception
No prior seafood allergy
No known prior immunodeficiency or autoimmune disease
No other active cancer except basal cell or squamous cell skin cancer
PRIOR CONCURRENT THERAPY:
Biologic therapy:
At least 6 weeks since prior immunotherapy
No prior vaccine with any of the antigens in this study
Chemotherapy:
See Disease Characteristics
At least 4 weeks since prior chemotherapy
No concurrent chemotherapy
Endocrine therapy:
See Disease Characteristics
Radiotherapy:
See Disease Characteristics
At least 4 weeks since prior radiotherapy
No concurrent radiotherapy
Surgery:
See Disease Characteristics
At least 4 weeks since prior surgery
Concurrent surgery for local recurrence allowed if patient remains disease free | Entailment |
A patient who underwent T-cell transfer therapy in the past 2 weeks would be excluded from the primary trial. | Must be 4 weeks since all of the following treatments (recovered from toxicity of prior treatment to Grade 1, excluding alopecia):
immunotherapy; | Entailment |
Patients with Cancer that has spread from a breast tumor to their bone marrow are excluded from the primary trial. | No histologically proven bone marrow metastasis | Entailment |
Cohort 2 of the primary trial and the secondary trial are test groups. | INTERVENTION 1:
Glutamine
10 grams three times a day (orally) for four days and then stop
glutamine: 10 grams three times a day (orally) for four days and then stop
INTERVENTION 2:
Placebo
10 grams three times a day (orally) for four days and then stop
Placebo: 10 grams three times a day (orally) for four days and then stop
INTERVENTION 1:
Mammography Only
For this reporting arm, the interpretation and analysis was done with mammography only.
INTERVENTION 2:
Gamma Imaging
For this reporting arm, the interpretation and analysis was done with gamma imaging only. | Contradiction |
the secondary trial has more patients cohorts than the primary trial. | INTERVENTION 1:
Electronic Brachytherapy
Radiation therapy was delivered using the 510(k) cleared Xoft Axxent System. Accelerated partial breast irradiation is the method of radiation therapy administration that has been commonly used by physicians using Iridium-192, but was FDA cleared for use prior to commencing study enrollment using an electronic source.
INTERVENTION 1:
Initial Cohort
Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG Subcutaneous administration 5 doses of 300 micrograms
Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG: All research participants will receive the Mimotope P10s-PADRE/MONTANIDE ISA 51 VG vaccine via subcutaneous (SC) injection following the schedule
INTERVENTION 2:
Escalation Cohort
Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG Subcutaneous administration of 5 doses of 500 micrograms
Vaccination with Mimotope P10s-PADRE/MONTANIDE ISA 51 VG: All research participants will receive the Mimotope P10s-PADRE/MONTANIDE ISA 51 VG vaccine via subcutaneous (SC) injection following the schedule | Entailment |
Patients will have to undergo an MRI scan for before entry for both the secondary trial and the primary trial, for the primary trial patients will also need to have a brain MR and PET imaging, after study entry. | Inclusion Criteria:
Ability to undergo brain MR and PET imaging
Subjects with prior resection of brain metastases with progressions on brain MRI.
Inclusion Criteria:
clinical and imaging complete or near-complete response on MRI | Entailment |
histologically confirmed invasive ductal breast cancer would result in exclusion from the primary trial, but not from the secondary trial. | Exclusion Criteria:
No histologic evidence of EIC | Contradiction |
the primary trial uses a 3 week cycle for SB-715992 administration. | INTERVENTION 1:
SB-715992
The eligible participants were administered Ispinesib, intravenously as a one-hour infusion on Day 1 of every 21-day treatment cycle, at a dose of 18 mg/m^2. The dosing was repeated for up to multiple cycles, until disease progression or removal from treatment due to an unacceptable toxicity or withdrawal of consent. | Entailment |
Not all subjects in the primary trial and the secondary trial will be adminstered 4-8 mCi Tc-99m sestamibi. | INTERVENTION 1:
Overall Population
Each subject served as her own control, with imaging of each mass by both the test and control modalities. Specificity difference is a single measure for the overall ITD population.
INTERVENTION 1:
Molecular Breast Imaging
Molecular breast imaging performed after injection of 4 mCi Tc-99m sestamibi and again after 8 mCi Tc-99m sestamibi. | Entailment |
Women of any age can participate in the primary trial or the secondary trial. | Key Inclusion Criteria:
- Women with locally advanced, recurrent, or metastatic breast cancer along with confirmation of estrogen-receptor positive (ER+). Measurable disease defined as at least one lesion 10 mm by CT or MRI that can be accurately measured in at least one dimension (CT scan slice thickness 5 mm) OR Bone lesions: lytic or mixed (lytic + blastic) in the absence of measurable disease as defined above.
Key Exclusion Criteria:
- Patients who received more than one chemotherapy line. Patients with only non-measurable lesions other than lytic or mixed (lytic and blastic) bone metastasis.Previous treatment with exemestane, mTOR inhibitors, PI3K inhibitors or AKT inhibitors.
Inclusion Criteria:
Assigned female at birth;
18 years and older; | Contradiction |
Nausea and Death are two of the most common adverse events for patients in cohort 1 of the primary trial | Adverse Events 1:
Total: 7/26 (26.92%)
Febrile neutropenia 1/26 (3.85%)
Neutropenia 0/26 (0.00%)
Thrombocytopenia 0/26 (0.00%)
Cardiac failure congestive 0/26 (0.00%)
Extrasystoles 0/26 (0.00%)
Nausea 1/26 (3.85%)
Abdominal pain 0/26 (0.00%)
Constipation 0/26 (0.00%)
Gastrointestinal haemorrhage 0/26 (0.00%)
Death - unknown cause 1/26 (3.85%)
Thrombosis in device 0/26 (0.00%) | Entailment |
the primary trial recorded a multitude of patients with chest pain, whereas the secondary trial observed only one patient with abdominal pain. | Adverse Events 1:
Angina pectoris * 1/298 (0.34%)
Adverse Events 1:
Abdominal pain 1/38 (2.63%) | Contradiction |
Cohort 1 and 2 of the primary trial recorded exactly the same number of each type of adverse events. | Adverse Events 1:
Total: 17/94 (18.09%)
Anaemia 2/94 (2.13%)
Lymphadenopathy 0/94 (0.00%)
Angina pectoris 0/94 (0.00%)
Ischaemic cardiomyopathy 0/94 (0.00%)
Myocardial infarction 1/94 (1.06%)
Haemorrhoids 1/94 (1.06%)
Ileus 1/94 (1.06%)
Nausea 1/94 (1.06%)
Vomiting 1/94 (1.06%)
Asthenia 1/94 (1.06%)
Disease progression 0/94 (0.00%)
Oedema peripheral 1/94 (1.06%)
Adverse Events 2:
Total: 9/39 (23.08%)
Anaemia 2/39 (5.13%)
Lymphadenopathy 0/39 (0.00%)
Angina pectoris 0/39 (0.00%)
Ischaemic cardiomyopathy 0/39 (0.00%)
Myocardial infarction 1/39 (2.56%)
Haemorrhoids 1/39 (2.56%)
Ileus 1/39 (2.56%)
Nausea 1/39 (2.56%)
Vomiting 1/39 (2.56%)
Asthenia 1/39 (2.56%)
Disease progression 0/39 (0.00%)
Oedema peripheral 1/39 (2.56%) | Entailment |
the primary trial is a phase II trial in which all participants will recieve topical fluocinonide 0.05% cream to apply to their genitalia twice daily for two weeks. | INTERVENTION 1:
Supportive Care (Fluocinonide Cream)
This is a single-arm, single-stage, open-label phase II trial of topical fluocinonide 0.05% cream to improve vaginal symptoms.
All subjects will receive topical fluocinonide 0.05% cream to apply twice daily for two weeks and then once daily for two weeks to the vagina. The duration of treatment will be 4 weeks. | Entailment |
the primary trial has a 5 year long intervention, the duration of the secondary trial is only a single day after removal of the drains. | INTERVENTION 1:
Tamoxifen
Tamoxifen 20mg orally daily for 5 years
INTERVENTION 2:
Ovarian Function Suppression
Tamoxifen 20mg orally daily or Exemestane 25mg orally daily for 5 years plus ovarian function suppression (OFS; triptorelin (GnRH analogue) 3.75 mg by im injection q28 days for 5 years; or surgical oophorectomy; or ovarian irradiation)
Note: Data were collected separately for the T+OFS and E+OFS participants in the parent study, IBCSG 24-02 (SOFT). The sample size for this Co-SOFT substudy was small, so the analysis plan was revised to pre-specify collective analysis for all patients receiving OFS.
INTERVENTION 1:
Single Drain
Insertion of a single drain: A negative pressure drain will be inserted below the lower flap directing to the axilla in the single drain group.
Ultrasonography after removal of the drains: One day after removal of the drains seroma under the flaps and in the axilla will be examined by ultrasonography.
Insertion of a single drain: A negative pressure drain will be inserted below the lower flap directing to the axilla.
Ultrasonography after removal of the drains: One day after removal of the drains seroma under the flaps and in the axilla will be examined by ultrasonography.
INTERVENTION 2:
Double Drain
Insertion of double drains: Two negative pressure drains will be inserted into the axilla and below the lower flap in the double drains group.
Ultrasonography after removal of the drains: One day after removal of the drains seroma under the flaps and in the axilla will be examined by ultrasonography.
Insertion of double drains: Two drains will be inserted into the axilla and below the lower flap in the double drains group.
Ultrasonography after removal of the drains: One day after removal of the drains seroma under the flaps and in the axilla will be examined by ultrasonography. | Contradiction |
the secondary trial and the primary trial both have a placebo arm and a test arm. | INTERVENTION 2:
Fulvestrant & Placebo
Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus placebo daily x 12 cycles.
Fulvestrant: Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).
If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.
Placebo: Placebo for Everolimus (2 tablets) daily x 12 cycles. Placebo manufactured to mimic everolimus tablet.
INTERVENTION 1:
Arm A: Triptorelin + Letrozol
Arm A: Triptorelin 3.75 mg i.m. on day 1 every 28 days for 6 cycles + letrozole 2.5 mg/day orally for 6 cycles
Triptorelin: Triptorelin 3.75 mg injected into the muscle on day 1 every 28 days for 6 cycles (1 cycle= 28 days)
Letrozole: Letrozole 2.5 mg orally every day for 6 cycles
INTERVENTION 2:
Arm B: Degarelix + Letrozol
Arm B: Degarelix 240 mg s.c. on day 1 of cycle 1, followed by 80 mg s.c. on day 1 of cycles 2 to 6 + letrozole 2.5 mg every day orally for 6 cycles
Degarelix: Degarelix 240 mg injected under the skin given as two injections of 120 mg on the first day of treatment, followed by injection of 80 mg on day 1 of cycles 2 to 6 (1 cycle=28 days)
Letrozole: Letrozole 2.5 mg orally every day for 6 cycles | Contradiction |
Throughout the duration of the primary trial, pariticpants receive increasing doses of Fulvestrant. | INTERVENTION 1:
Fulvestrant 250 mg + Tipifarnib 300 mg
Patients receive fulvestrant 250 mg intramuscularly on day 1 and oral tipifarnib 300 mg twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity | Contradiction |
Patients that have previously been trated with bevacizumab are not eligible for the primary trial. | Exclusion Criteria:
Prior treatment with Abraxane®, carboplatin or bevacizumab, or any taxane for metastatic breast cancer; | Entailment |
the secondary trial and the primary trial both use Pathologic complete response (pCR) as their outcome measure, and use a 6 month time frame. | Outcome Measurement:
Clinical Benefit Rate (CR + PR + SD > 6 Months).
To determine the clinical benefit rate (Complete Response + Partial Response + Stable Disease > 6 months) per Response Evaluation Criteria in Solid tumors (RECIST version 1.0). of MPA monotherapy and MPA + low dose oral cyclophosphamide and methotrexate (ldoCM) in patients with refractory hormone receptor negative metastatic breast cancer. This will show the percent of patients who had Clinical Benefit and the Exact 95% Confidence Interval.
Time frame: baseline through end of study, up to 3 years
Outcome Measurement:
Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort
Pathologic complete response (pCR) defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of 24 weeks of treatment by local assessment (ypT0/Tis ypN0). Patients who experienced progression of disease while undergoing neoadjuvant therapy, or who did not receive surgery for any reason, or received antineoplastic treatment other than study drug(s) before surgery were considered as non-responders for the calculation of pCR rate.
Time frame: After 24 weeks of treatment | Contradiction |
Patients with stage 3 Cervical carcinoma are excluded from the primary trial. | Inclusion Criteria:
no prior or current neoplasm except for non-melanoma skin cancer, or in situ cancer of the cervix; | Entailment |
2 of the patients in the primary trial were either symptomatic, but able to swallow a modified diet; symptomatic and unable to aliment or hydrate orally or had symptoms associated with life-threatening consequences. | Outcome Measurement:
Number of Participants With Stomatitis Grade 2
The incidence of grade 2 stomatitis was reported. Grade 1 = minimal symptoms, normal diet; grade 2 = symptomatic, but able to swallow a modified diet; grade 3 = symptomatic and unable to aliment or hydrate orally; and grade 4 = symptoms associated with life-threatening consequences.
Time frame: 56 days
Results 1:
Arm/Group Title: Dexamethasone Based Mouthwash
Arm/Group Description: Participants swished and spat 10mL of 0.5mg/5mL dexamethasone steroid mouthwash (investigational treatment) 4 times daily (qid) orally for 2 minutes each for 8 weeks. Participants remained without food or drink (NPO) for one hour after administration of the mouthwash. Also, participants received everolimus 10 mg and exemstane 25 mg (study treatments) according to local regulations.
Overall Number of Participants Analyzed: 86
Measure Type: Number
Unit of Measure: Participants Stomatitis grade >=2: Yes: 2
Stomatitis grade >=2: No: 83
Stomatitis grade >=2: Not evaluable: 1 | Entailment |
Between all cohorts in the primary trial and the secondary trial Omega-3-fatty Acids are only used in one cohort. | INTERVENTION 1:
Participants With Stage 0-III Breast Cancer
Women with Stage 0-III breast cancer, treated with breast conserving surgery or mastectomy and clear margins, will receive 15 doses of radiation over three weeks.
Hypofractionated Simultaneous Integrated Boost Radiotherapy: Participants will receive radiotherapy treatments to the whole breast or chest wall to a dose of 2.66 Gy per day x 15 fractions simultaneously with a boost treatment. The boost treatment will be given on the same days as the whole breast treatment. The lumpectomy cavity + scar (in lumpectomy patients) or chest wall scar (mastectomy patients) will receive 0.54 Gy per day x 15 fractions.
INTERVENTION 1:
Arm I (Omega-3-fatty Acid)
Patients receive oral omega-3-fatty acid twice daily (BID) or three times daily (TID) for 24 weeks in the absence of disease progression or unacceptable toxicity
INTERVENTION 2:
Arm II (Placebo)
Patients receive oral placebo BID or TID for 24 weeks in the absence of disease progression or unacceptable toxicity | Entailment |
Cohort 2 of the primary trial receive a higher dose of Ixabepilone, at a higher frequency, than cohort 1, | INTERVENTION 1:
Ixabepilone 25 mg^m2 + Epirubicin 75 mg^m2
Participants received 25 mg/m^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m^2 epirubicin every 21 days.
INTERVENTION 2:
Ixabepilone 30 mg^m2 + Epirubicin 75 mg^m2
Participants received 30 mg/m^2 Ixabepilone as a 3-hour IV infusion following a 3- to 5-minute IV infusion of 75 mg/m^2 epirubicin every 21 days. | Contradiction |
There results section indicates there were no patients in the primary trial with 0 adverse events. | Outcome Measurement:
Number of Participants With Adverse Events (AEs)
Number of participants with any grade of adverse events (AEs) graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Daratumumab
Time frame: From first dose to 30 days post last dose (up to 34 months)
Results 1:
Arm/Group Title: Nivolumab + Daratumumab (TNBC)
Arm/Group Description: Triple-negative breast cancer (TNBC) treated with Triple-negative breast cancer (TNBC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)
Overall Number of Participants Analyzed: 41
Measure Type: Count of Participants
Unit of Measure: Participants 41 100.0%
Results 2:
Arm/Group Title: Nivolumab + Daratumumab (NSCLC)
Arm/Group Description: Non-small cell lung cancer (NSCLC) treated with Nivolumab IV 240 mg Q2W (weeks 3 to 24) + Daratumumab IV 16 mg/kg Q1W (weeks 1 to 8), Daratumumab IV 16 mg/kg Q2W (weeks 9-24)
Overall Number of Participants Analyzed: 21
Measure Type: Count of Participants
Unit of Measure: Participants 21 100.0% | Entailment |
The interventions in the primary trial and the secondary trial are so different that it is not possible or useful to compare them. | INTERVENTION 1:
Molecular Breast Imaging
Molecular breast imaging performed after injection of 4 mCi Tc-99m sestamibi and again after 8 mCi Tc-99m sestamibi.
INTERVENTION 1:
Control Arm
Mail
Standard Reminder Postcard
INTERVENTION 2:
Family Physician Reminder Letter Arm
Mail
Standard Reminder Postcard
Family Physician Reminder Letter | Entailment |
There was over 14 weeks difference in Progression-free Survival between the minimum and maximum PFS in the primary trial. | Outcome Measurement:
Progression-free Survival (PFS)
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier survival curves will be used. A 95% confidence interval for the median PFS will be calculated. A lower bound greater than 8 months would be strong evidence that Nab-Paclitaxel- bevacizumab induction therapy followed by bevacizumab-erlotinib hydrochloride maintenance therapy is superior to paclitaxel and bevacizumab. However, a median PFS of 13 months or greater (regardless of whether the 95% confidence interval for the median extends below 8 months) could also indicate promising results.
Time frame: Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 8 years
Results 1:
Arm/Group Title: Tx (Chemo, MoAb, and Enzyme Inhibitor)
Arm/Group Description: INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity.
paclitaxel albumin-stabilized nanoparticle formulation: Given IV
bevacizumab: Given IV
erlotinib hydrochloride: Given PO
Overall Number of Participants Analyzed: 55
Median (95% Confidence Interval)
Unit of Measure: Months 9.1 (7.2 to 11.1) | Entailment |
Patients that are not willing to sign and give written informed consent for participation of the primary trial or the secondary trial will not be made to take part. | Inclusion Criteria:
Women >=18 years of age
HER2-negative metastatic breast cancer
Previous adjuvant chemotherapy or hormonal treatment
>=1 measurable target lesion
Exclusion Criteria:
Previous treatment with chemotherapy, an anti-angiogenic agent, or a biologic therapy for advanced or metastatic cancer
Radiation therapy within 4 weeks of study treatment start or insufficient recovery from the effects of prior radiation therapy
Central nervous system metastases
Other malignancy within last 5 years, except cured basal cell carcinoma of skin and carcinoma in situ of uterine cervix
Serious concurrent infection
All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines. | Entailment |
The Median length of time that a patient in Arm A of the primary trial survived after receiving a TNBC diagnosis was 6 months. | Outcome Measurement:
Progression-free Survival (PFS)
Analysis of the primary endpoint, PFS, will be performed using Cox regression with treatment group as a single covariate.
Time frame: From randomization to the earliest date of documentation of disease progression, up to 5 years
Results 1:
Arm/Group Title: Arm A
Arm/Group Description: Patients receive oral capecitabine twice daily on days 1-14 and oral lapatinib ditosylate once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. lapatinib ditosylate: Given PO and capecitabine: Given PO
Overall Number of Participants Analyzed: 19
Median (95% Confidence Interval)
Unit of Measure: Median survival and CI in months 6.0 (4.3 to 8.6) | Contradiction |
The majority of patients in the primary trial experienced at least one adverse event. | Adverse Events 1:
Total: 20/88 (22.73%) | Contradiction |
In total more than 5 patients in the primary trial and the secondary trial experienced Earache. | Adverse Events 1:
Total: 107/383 (27.94%)
Anaemia 4/383 (1.04%)
Febrile neutropenia 7/383 (1.83%)
Haemoytique anaemia 0/383 (0.00%)
Leukopenia 1/383 (0.26%)
Neutropenia 6/383 (1.57%)
Thrombocytopenia 2/383 (0.52%)
Anginal pectoris 1/383 (0.26%)
Cardiomyopathy 0/383 (0.00%)
Ear pain 0/383 (0.00%)
Abdominal distension 1/383 (0.26%)
Abdominal pain 6/383 (1.57%)
Adverse Events 2:
Total: 85/383 (22.19%)
Anaemia 3/383 (0.78%)
Febrile neutropenia 2/383 (0.52%)
Haemoytique anaemia 0/383 (0.00%)
Leukopenia 0/383 (0.00%)
Neutropenia 1/383 (0.26%)
Thrombocytopenia 1/383 (0.26%)
Anginal pectoris 0/383 (0.00%)
Cardiomyopathy 1/383 (0.26%)
Ear pain 1/383 (0.26%)
Abdominal distension 0/383 (0.00%)
Abdominal pain 3/383 (0.78%)
Adverse Events 1:
Total: 427/2002 (21.33%)
ANAEMIA 13/2002 (0.65%)
BONE MARROW FAILURE 1/2002 (0.05%)
DISSEMINATED INTRAVASCULAR COAGULATION 1/2002 (0.05%)
FEBRILE NEUTROPENIA 1/2002 (0.05%)
THROMBOCYTOPENIA 11/2002 (0.55%)
ACUTE CORONARY SYNDROME 3/2002 (0.15%)
ANGINA PECTORIS 1/2002 (0.05%)
CARDIAC ARREST 1/2002 (0.05%)
CARDIAC FAILURE 1/2002 (0.05%)
CARDIAC TAMPONADE 1/2002 (0.05%)
Adverse Events 2:
Total: 36/181 (19.89%)
ANAEMIA 0/181 (0.00%)
BONE MARROW FAILURE 0/181 (0.00%)
DISSEMINATED INTRAVASCULAR COAGULATION 0/181 (0.00%)
FEBRILE NEUTROPENIA 0/181 (0.00%)
THROMBOCYTOPENIA 10/181 (5.52%)
ACUTE CORONARY SYNDROME 1/181 (0.55%)
ANGINA PECTORIS 0/181 (0.00%)
CARDIAC ARREST 0/181 (0.00%)
CARDIAC FAILURE 0/181 (0.00%)
CARDIAC TAMPONADE 0/181 (0.00%) | Contradiction |
the primary trial and the secondary trial recorded the exact same number of cases of nausea. | Adverse Events 1:
Nausea 1/23 (4.35%)
Adverse Events 1:
Nausea * 1/52 (1.92%) | Entailment |
Candidates for the primary trial do not need to meet a specific life expectancy criteria. | Life expectancy
Not specified | Entailment |
Patients in the primary trial will not be made to take Herceptin© (trastuzumab) or paclitaxel intravenously like those in the secondary trial. | INTERVENTION 1:
Diagnostic (18F-FLT)
Patients undergo 18F-FLT PET/CT at baseline (prior to chemotherapy, FLT-1), early therapy (5-10 days after the initiation of the first course of chemotherapy, FLT-2), and post therapy (within 3 weeks prior to surgery, FLT-3). Patients undergo standard surgical resection of residual tumor following completion of neoadjuvant chemotherapy.
Fluorothymidine F-18: Undergo 18F-FLT PET/CT
Positron Emission Tomography: Undergo 18F-FLT PET/CT
Computed Tomography: Undergo 18F-FLT PET/CT
Laboratory Biomarker Analysis: Correlative studies
INTERVENTION 1:
Herceptin© + Taxane
Part 1: Herceptin© (trastuzumab) intravenously+ paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.
Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to Herceptin© (trastuzumab) alone once every 3 weeks until DP or subject withdrawal .
INTERVENTION 2:
MYL-1401O Trastuzumab + Taxane
Part 1:Myl 1401OTrastuzumab Intravenously + paclitaxel 80 mg/m2 weekly intravenously or docetaxel 75 mg/m2 intravenously once every three weeks (investigators choice) for 8 cycles then evaluate for primary endpoint.
Part 2: If SD or PR, CR at cycle 9 (week 24) proceed to Myl 1401O( Mylan Trastuzumab) alone once every 3 weeks until DP or subject withdrawal. | Entailment |
Patients must have a life expectancy over half a year to participate in the primary trial. | Inclusion Criteria:
Patient who have estimated life expectancy of more than six months | Entailment |
A 30% of patients in the primary trial suffered a life-threatening reaction to an infection. | Adverse Events 1:
Total: 9/90 (10.00%)
Febrile neutropenia 2/90 (2.22%)
Ascites 0/90 (0.00%)
Nausea 0/90 (0.00%)
Vomiting 0/90 (0.00%)
Death NOS 1/90 (1.11%)
Fever 0/90 (0.00%)
Other general disorders, administration site conditions 0/90 (0.00%)
Other hepatobiliary disorders 1/90 (1.11%)
Lung infection 2/90 (2.22%)
Sepsis 2/90 (2.22%)
Spinal fracture 0/90 (0.00%)
Adverse Events 2:
Total: 12/89 (13.48%)
Febrile neutropenia 0/89 (0.00%)
Ascites 1/89 (1.12%)
Nausea 1/89 (1.12%)
Vomiting 1/89 (1.12%)
Death NOS 2/89 (2.25%)
Fever 1/89 (1.12%)
Other general disorders, administration site conditions 1/89 (1.12%)
Other hepatobiliary disorders 0/89 (0.00%)
Lung infection 0/89 (0.00%)
Sepsis 1/89 (1.12%)
Spinal fracture 1/89 (1.12%) | Contradiction |
The only adverse event observed in Patients from both the secondary trial and the primary trial, was Endocervical cancer. | Adverse Events 1:
Total: 14/69 (20.29%)
Febrile neutropenia 0/69 (0.00%)
Anaemia 0/69 (0.00%)
Atrial fibrillation 1/69 (1.45%)
Cardiopulmonary failure 0/69 (0.00%)
Supraventricular extrasystoles 1/69 (1.45%)
Abdominal pain 1/69 (1.45%)
Intestinal obstruction 0/69 (0.00%)
Vomiting 1/69 (1.45%)
Chills 1/69 (1.45%)
Oedema peripheral 0/69 (0.00%)
Pyrexia 1/69 (1.45%)
Adverse Events 2:
Total: 17/66 (25.76%)
Febrile neutropenia 6/66 (9.09%)
Anaemia 1/66 (1.52%)
Atrial fibrillation 1/66 (1.52%)
Cardiopulmonary failure 1/66 (1.52%)
Supraventricular extrasystoles 0/66 (0.00%)
Abdominal pain 0/66 (0.00%)
Intestinal obstruction 1/66 (1.52%)
Vomiting 0/66 (0.00%)
Chills 0/66 (0.00%)
Oedema peripheral 1/66 (1.52%)
Pyrexia 0/66 (0.00%)
Adverse Events 1:
Total: 0/244 (0.00%)
Pregnancy *0/244 (0.00%)
Endocervical cancer *0/244 (0.00%)
Nosocomial pneumonia *0/244 (0.00%)
Venous thrombosis *0/244 (0.00%) | Contradiction |
Patients with HER2 negative tumours are eligible for the primary trial but not for the secondary trial | Inclusion Criteria:
Inoperable estrogen receptor positive and HER2 negative breast cancer.
Inclusion Criteria:
Patients with newly diagnosed stage I (T>1cm), II or III triple negative breast cancer who have not had definitive breast surgery or received systemic chemotherapy | Contradiction |
the secondary trial and the primary trial do not require participants to be of a particular ethnicity, to be able to speak a specific language or to be above a certain height threshold. | Inclusion criteria:
Female patients >=18 years with proven diagnosis of HER2-overexpressing, histologically confirmed breast cancer
Locally advanced or metastatic disease
Must have disease that can be evaluated according to RECIST 1.1 (Response Evaluation Criteria for Solid Tumours version 1.1)
For trastuzumab pre-treated patients, must have failed prior trastuzumab treatment
Investigator-confirmed diagnosis of Inflammatory Breast Cancer
Must have biopsiable disease
Exclusion criteria:
Prior treatment with HER2-targeted small molecules or antibodies other than trastuzumab (which must have been given in the trastuzumab-failure study population)
Must not have received prior vinorelbine treatment
INCLUSION CRITERIA:
Postmenopausal female.
Postmenopausal defined as no menses for at least 12 months or bilateral oophorectomy. In unclear cases, (e.g. 50 year old who has had hysterectomy) chemical confirmation of postmenopausal status may be confirmed with follicle stimulating hormone (FSH) greater than 35 U/L.
Elevated risk for developing invasive breast cancer by virtue of one of the following criteria:
Gail Model risk of greater than or equal to 1.7% over 5 years from study entry. (This is the same minimum level of risk required for a subject to be eligible for the recently completed NSABP-P1 tamoxifen breast cancer prevention trial).
Lobular neoplasia.
Atypical ductal hyperplasia.
DCIS (ductal carcinoma in situ) that has been previously treated with mastectomy or lumpectomy and radiation, +/- tamoxifen.
Deleterious mutations in BRCA1 or 2 OR A priori risk assessment of 20% chance or greater of carrying BRCA1/2 gene mutation. The BRCAPRO and Couch model will both be used to asses this risk. If a woman has a 20% risk of carrying a BRCA1/2 mutation by either model, she will meet eligibility criteria.
Prior stage I or II breast cancer at least 2 years out from treatment for invasive disease and no prior use of aromatase inhibitors.
Subjects should be willing to abstain from use of hormonal therapies (e.g. tamoxifen, hormone replacement therapy, oral contraceptive pills, hormone-containing intrauterine devices (IUDs). E-string is acceptable). Venlafaxine will be offered as supportive care for women with menopausal symptoms.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Subject has been counseled regarding her options and has signed the informed consent document.
Baseline dual-emission x-ray absorptiometry (DEXA) scan with bone mineral density (BMD) T-score greater than or equal to 2.5 at antero posterior (AP) spine.
Hemoglobin greater than or equal to 11 g/dl.
Creatinine less than 1.5 times the upper limits of normal.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) less than 2.5 times upper limit of normal.
No investigational agent for the past 30 days.
If history of cancer (other than squamous or basal cell skin cancers), subject must have no evidence of disease at time of enrollment AND no history of cancer directed treatment in the 2 years preceding enrollment.
EXCLUSION CRITERIA:
Current or recent chronic use (within 3 months) of hormonal medications, e.g. oral contraceptive pills, hormone replacement therapy, tamoxifen, raloxifene, IUD with progestins or corticosteroids. (Subjects on chronic topical or inhaled steroids will be eligible for the study.) Current use of phenytoin, carbamazepine, rifampin due to increased estrogen metabolism.
History of clotting or bleeding disorder.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to exemestane (e.g. anastrozole, letrozole, formestane).
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. | Entailment |
Intervention 1 of the primary trial require participants to take 300 mg alpelisib once daily. | INTERVENTION 1:
Alpelisib + Letrozole
Participants took alpelisib 300 mg once daily plus letrozole 2.5 mg once daily. | Entailment |
the primary trial and the secondary trial have the same number of study groups, and are both testing the effectiveness of Full-Field Digital Mammography. | 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).
INTERVENTION 1:
Active Control Group
Health Education Active Control Group
INTERVENTION 2:
My Surgical Success Treatment Group
My Surgical Success Intervention Group | Contradiction |
Patients under the age of 18, wanting to participate in the primary trial, must discontinue any Antitumoral hormonal treatment prior to study entry, and have a life expectancy of more than 3 months. | Inclusion Criteria:
Antitumoral hormonal treatment must be discontinued prior to enrollment.
Estimated life expectancy of at least 3 months.
Female participants must be at least 18 years of age. | Contradiction |
Females over the age of 20 with no prior chemotherapy with therapeutic intent for current cancer, are eligible for the primary trial. | Inclusion Criteria:
No prior chemotherapy, endocrine therapy or radiation therapy with therapeutic intent for this cancer
Female subjects age 18 - 70 years | Entailment |
Cohort 2 of the primary trial recieves Doxorubicin, cyclophosphamide, Herceptin and docetaxel throughout the cycles of the study. | INTERVENTION 2:
AC Followed by Docetaxel + Herceptin (AC→TH)
Doxorubicin 60 mg/m² IV bolus injection in combination with cyclophosphamide 600 mg/m² IV bolus Injection on Day 1 of every 3 weeks for 4 cycles. Herceptin 4 mg/kg IV infusion on Day 1 of Cycle 5, followed by Herceptin 2 mg/kg by IV infusion weekly starting from Day 8; and docetaxel 100 mg/m² IV infusion on Day 2 of Cycle 5, then on Day 1 of every 3 weeks for all subsequent cycles ( total 4 cycles). After completion of the last cycle of chemotherapy, Herceptin 6 mg/kg IV infusion was administered every 3 weeks until 1 year from date of initial Herceptin dose. | Entailment |
At least 400 participants in the primary trial receiving an oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusions of Vinorelbine 25 mg/meter^2 (meter=m) had a PFS over 9 months. | Outcome Measurement:
Progression-free Survival (PFS)
PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by investigator according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment.
Only data collected until the cut-off date for RECIST 1.1 based endpoints (08Jun2013) were considered.
Progression of disease was determined if at least 1 of the following criteria applied:
At least a 20% increase in the sum of the diameters (SoD) of target lesions taking as reference the smallest SoD recorded since the treatment started, together with an absolute increase in the SoD of at least 5 mm
Appearance of 1 or more new lesions
Unequivocal progression of existing non-target lesions
Time frame: From randomization (07Sep2010) until disease progression, death or data cut-off (08Jun2013); Up to 34 months
Results 1:
Arm/Group Title: Afatinib + Vinorelbine (AV)
Arm/Group Description: Participants received oral treatment of film-coated Afatinib tablet at a starting dose of 40 milligram (mg) once daily and weekly 10 minutes intravenous infusion of Vinorelbine 25 mg/meter^2 (meter=m) on days 1, 8, 15, and 22 of each course. The treatment was administered in treatment courses of 28 days. For Afatinib, a protocol-defined dose-reduction scheme was to be followed if a participant experienced certain pre-specified adverse events. From 26 April 2013, any participant who had been randomised to the AV arm stopped treatment, had the option to switch to Trastuzamb + Vinorelbine.
Overall Number of Participants Analyzed: 339
Median (Inter-Quartile Range)
Unit of Measure: Months 5.49 (3.55 to 9.07) | Contradiction |
Patients with unexplained fever below thirty eight degrees Celsius may be included in the secondary trial and the primary trial. | Exclusion Criteria:
Active infection or unexplained fever >38.5°C during screening.
Inclusion Criteria:
Tissue diagnosis of a breast carcinoma
The oncologist must have prescribed doxorubicin as part of the planned chemotherapy regimen
Have acceptable organ function within 14 days of enrollment defined as:
liver function: total bilirubin, AST and ALT within normal institutional limits
kidney function: estimated Creatinine Clearance > 60 ml/min calculated creatinine clearance (for females) - formula: (140 - age) x weight x .85 divided by (sCr x 72)
At least 18 years old
Patient must have given written informed consent indicating an understanding of the investigational nature of the study
Agrees not to consume grapefruit juice while on the study
Exclusion Criteria:
Known allergy to enalapril
Taking any known P450 cytochrome inducers or inhibitors
Taking any herbal supplements while on the study or the week prior to receiving doxorubicin
Taking an ace-inhibitor or angiotensin receptor blocker
Pregnant or lactating. Enalapril is Pregnancy Categories C (first trimester) and D (second and third trimesters) | Contradiction |
Patients must have ductal carcinoma, that can be felt by touch to be eligible for the primary trial. | Inclusion Criteria:
Histologic diagnosis of palpable invasive breast cancer or ductal carcinoma in situ | Contradiction |
the secondary trial and the primary trial do not both use Clinical Benefit Rate as their outcome measure, and they do not use the same time frame. | Outcome Measurement:
Clinical Benefit Rate (CR + PR + SD > 6 Months).
To determine the clinical benefit rate (Complete Response + Partial Response + Stable Disease > 6 months) per Response Evaluation Criteria in Solid tumors (RECIST version 1.0). of MPA monotherapy and MPA + low dose oral cyclophosphamide and methotrexate (ldoCM) in patients with refractory hormone receptor negative metastatic breast cancer. This will show the percent of patients who had Clinical Benefit and the Exact 95% Confidence Interval.
Time frame: baseline through end of study, up to 3 years
Outcome Measurement:
Pathological Complete Response (pCR) Per Investigator Assessment for Alpelisib vs. Placebo for PIK3CA Mutant Cohort
Pathologic complete response (pCR) defined as absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of 24 weeks of treatment by local assessment (ypT0/Tis ypN0). Patients who experienced progression of disease while undergoing neoadjuvant therapy, or who did not receive surgery for any reason, or received antineoplastic treatment other than study drug(s) before surgery were considered as non-responders for the calculation of pCR rate.
Time frame: After 24 weeks of treatment | Entailment |
Patients with histologically confirmed, newly diagnosed stage 0 bilateral breast cancer cannot take part in the primary trial, but may still be eligible for the secondary trial. | Patient has bilateral breast cancer or metastatic disease or inflammatory breast cancer
Inclusion Criteria:
Survivors: Latina, has been diagnosed with breast cancer, speaks English or Spanish, has a Caregiver who is willing to participate.
Caregivers: a primary caregiver for a Latina breast cancer survivor, speak English or Spanish
Exclusion Criteria:
Inability to understand spoken English and/or Spanish and/or
Cognitive impairment that precludes informed consent (determined by the PIs or Co-Investigators who are mental health professionals). | Entailment |
Patients in the primary trial and the secondary trial are administered daily oral medication. | INTERVENTION 1:
Usual Care
Usual Care is the comparison Clinic Patients, where there is no change in their standard or usual care.
INTERVENTION 2:
BreastCARE Intervention
Intervention Clinic Patients: The participants will answer questions on the tablet-PC to calculate their breast cancer risk.
Intervention Patient Report. Once the patient completes the BreastCare Computer survey, the program will immediately generate a personal feedback report containing information about her risk factors and recommendations to reduce her risk. This report will be printed and given to the patients before she meets with her doctor.
BreastCARE : The physician will receive a physician report that contains information similar to the patient report.
Patients receive oral vitamin D (2000 IU) once daily for 12 months. | Contradiction |
No less than 2 patients from either cohorts of the primary trial felt nauseous. | Adverse Events 1:
NAUSEA 1/101 (0.99%)
Adverse Events 2:
NAUSEA 0/103 (0.00%) | Contradiction |
There were 2 instances of patients with Atrial tachycardia in the primary trial. | Adverse Events 1:
Total: 3/31 (9.68%)
Edema: limb * 2/31 (6.45%)
Neutrophils/granulocytes (ANC/AGC) * 0/31 (0.00%)
Cardiac General - Other (Specify, __) * [1]0/31 (0.00%)
Cardiac General - Other (Specify, __) * [2]0/31 (0.00%)
Left ventricular diastolic dysfunction * 0/31 (0.00%)
Supraventricular and nodal arrhythmia - Atrial tachycardia/Paroxysmal Atrial Tachycardia * 0/31 (0.00%)
Adverse Events 2:
Total: 8/25 (32.00%)
Edema: limb * 1/25 (4.00%)
Neutrophils/granulocytes (ANC/AGC) * 0/25 (0.00%)
Cardiac General - Other (Specify, __) * [1]1/25 (4.00%)
Cardiac General - Other (Specify, __) * [2]0/25 (0.00%)
Left ventricular diastolic dysfunction * 1/25 (4.00%)
Supraventricular and nodal arrhythmia - Atrial tachycardia/Paroxysmal Atrial Tachycardia * 0/25 (0.00%) | Contradiction |
10 of the patients in Cohort 1 of the primary trial suffered from Hypotension. | Adverse Events 1:
Hypotension 0/50 (0.00%) | Contradiction |
Only people who have previously been diagnosed with cancer and have no signs of cancer after finishing treatment are eliglbe for the primary trial, as long as they are over the age of 20. | Inclusion Criteria:
breast cancer survivors over 20 years-old | Entailment |
the secondary trial and the primary trial both used MRI and Letrozole for their interventions. | INTERVENTION 1:
Letrozole, Breast Enhancement, Safety
Single arm of healthy postmenopausal women to have two breast MRI (baseline and post-treatment). Letrozole of 12.5 mg/day is given for three successive days just prior to the second MRI.
INTERVENTION 1:
Healthy Volunteers
Healthy women will be screened for Magnetic Resonance Imaging (MRI) contraindications, and then undergo contrast injection, and SWIFT acquisition.
Magnetic resonance imaging: Patients and healthy volunteers will be first screened for MRI contraindications. The SWIFT MRI workflow will be performed as follows: | Contradiction |
Patients must have a confirmed Postmenopausal status, defined as a lack of menses for over a year, 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) | Entailment |
Any patients with breast cancer above stage, currently receiving radiation therapy or biotherapy are excluded from the primary trial. | Exclusion Criteria:
Patients with stage IV breast cancer or undergoing chemotherapy, radiation therapy, immunotherapy, or biotherapy for current breast cancer. | Entailment |
the primary trial and the secondary trial are both evaluating patient assisted imaging interventions. | 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.
INTERVENTION 1:
Overall Population
Each subject served as her own control, with imaging of each mass by both the test and control modalities. Specificity difference is a single measure for the overall ITD population. | Contradiction |
the secondary trial and the primary trial do not test the same modalities of cancer treatments. | 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 | Entailment |
The difference in Percentage of Participants With At Least 1 Adverse Event (AE) During the Treatment Period in both cohorts of the primary trial is less than 1%. | Outcome Measurement:
Percentage of Participants With At Least 1 Adverse Event (AE) During the Treatment Period
Participants were planned to receive a total of 18 cycles of SC Herceptin. An AE was defined as any untoward medical occurrence in a participant administered SC Herceptin. Examples included unfavorable/unintended signs and symptoms, new or exacerbated disease, recurrence of intermittent condition, deterioration in laboratory value or other clinical test, or adverse procedure-related events. The percentage of participants with at least 1 AE during the treatment period (regardless of severity or seriousness) was reported.
Time frame: From Day 1 up to 19 cycles (cycle length 3 weeks) (approximately 1 year)
Results 1:
Arm/Group Title: Cohort A: SC Herceptin by Needle/Syringe
Arm/Group Description: Participants received SC Herceptin by an assisted administration as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was taken from a single-use vial and injected by needle/syringe.
Overall Number of Participants Analyzed: 1864
Measure Type: Number
Unit of Measure: percentage of participants 88.6
Results 2:
Arm/Group Title: Cohort B: SC Herceptin by SID
Arm/Group Description: Participants received SC Herceptin as 600 mg every 3 weeks for a total of 18 doses/cycles. Each dose of SC Herceptin was administered from a pre-filled SID. The first administration was performed by an HCP. Subsequent doses were self-administered by participants who were willing and judged competent by the HCP.
Overall Number of Participants Analyzed: 709
Measure Type: Number
Unit of Measure: percentage of participants 89.0 | Entailment |
Although there is a much higher percentage of patients with Thrombocytopenia in the secondary trial than in cohort 1 of the primary trial, no robust comparisons can be made due to the significant differences in cohort sizes. | Adverse Events 1:
Total: 59/199 (29.65%)
Anaemia 7/199 (3.52%)
Thrombocytopenia 2/199 (1.01%)
Adverse Events 1:
Total: 6/8 (75.00%)
Thrombocytopenia 1/8 (12.50%) | Entailment |
Men with Left ventricular ejection fraction > 50% are excluded from participating in the primary trial. | LVEF 50% as measured by echocardiogram or MUGA scan
Male or female | Contradiction |
The highest number of occurences for any adverse event in both the primary trial and the secondary trial was 2. | Adverse Events 1:
Total: 39/2240 (1.74%)
Supraven.arrhyth. Atrial fibrillation 1/2240 (0.04%)
Cardiac ischemia/infarction 2/2240 (0.09%)
Valvular heart disease 1/2240 (0.04%)
Cardiac General - Other 2/2240 (0.09%)
Endocrine - Other 1/2240 (0.04%)
Ocular - Other 1/2240 (0.04%)
Colitis 2/2240 (0.09%)
Diarrhea 1/2240 (0.04%)
Dysphagia 1/2240 (0.04%)
Gastritis 1/2240 (0.04%)
Adverse Events 1:
Total: 6
Agranulocytosis 0/42 (0.00%)
Anaemia 2/42 (4.76%)
Febrile neutropenia 1/42 (2.38%)
Leukopenia 0/42 (0.00%)
Neutropenia 1/42 (2.38%)
Thrombocytopenia 1/42 (2.38%)
Cardio-respiratory arrest 0/42 (0.00%)
Pericardial effusion 1/42 (2.38%)
Gastric ulcer haemorrhage 0/42 (0.00%)
Melaena 0/42 (0.00%)
Fatigue 1/42 (2.38%)
Multi-organ failure 0/42 (0.00%)
Adverse Events 2:
Total: 13
Agranulocytosis 1/61 (1.64%)
Anaemia 1/61 (1.64%)
Febrile neutropenia 0/61 (0.00%)
Leukopenia 2/61 (3.28%)
Neutropenia 2/61 (3.28%)
Thrombocytopenia 1/61 (1.64%)
Cardio-respiratory arrest 1/61 (1.64%)
Pericardial effusion 0/61 (0.00%)
Gastric ulcer haemorrhage 1/61 (1.64%)
Melaena 1/61 (1.64%)
Fatigue 1/61 (1.64%)
Multi-organ failure 1/61 (1.64%) | Entailment |
the secondary trial exclusively uses radiotherapy in its intervention, whereas the primary trial gives its patient cohorts Stem Cell Transplants on the first day of the study. | INTERVENTION 1:
High-dose Chemotherapy
Carboplatin + Cyclophosphamide + Thiotepa
Carboplatin : Target AUC of 20, then divided into 4 doses given by vein (IV) days -6, -5, -4, -3 prior to stem cell infusion.
Thiotepa : 120 mg/m^2 by vein days -6, -5, -4, -3 prior to stem cell infusion.
Stem Cell Transplant : Stem Cell Transplant on Day 0.
Cyclophosphamide : 1.5 gm/m^2 by vein days -6, -5, -4, -3 prior to stem cell infusion.
INTERVENTION 1:
Samarium 153-EDTMP + Stem Cell Transplant
Samarium 153-EDTMP tracer dose = 30 millicurie (mCi) intravenous Day 1; or with study drug to bones, receive higher therapy dose of 153 Sm-EDTMP 7-14 days after tracer dose. Stem Cell Transplant Day 0, about 14-21 days after Samarium 153-EDTMP. | Contradiction |
Patients with Cervical carcinoma in situ are excluded from the primary trial. | Inclusion Criteria:
no prior or current neoplasm except for non-melanoma skin cancer, or in situ cancer of the cervix; | Contradiction |
There were no patients with paranasal sinus reactions in the primary trial. | Adverse Events 1:
Total: 21/107 (19.63%)
Febrile neutropenia * 10/107 (9.35%)
Neutropenia * 1/107 (0.93%)
Left ventricular dysfunction * 0/107 (0.00%)
Angina pectoris * 0/107 (0.00%)
Cardiac failure congestive * 0/107 (0.00%)
Diarrhoea * 2/107 (1.87%)
Abdominal strangulated hernia * 0/107 (0.00%)
Duodenal ulcer haemorrhage * 0/107 (0.00%)
Pyrexia * 1/107 (0.93%)
Adverse Events 2:
Total: 22/107 (20.56%)
Febrile neutropenia * 8/107 (7.48%)
Neutropenia * 6/107 (5.61%)
Left ventricular dysfunction * 3/107 (2.80%)
Angina pectoris * 1/107 (0.93%)
Cardiac failure congestive * 0/107 (0.00%)
Diarrhoea * 0/107 (0.00%)
Abdominal strangulated hernia * 1/107 (0.93%)
Duodenal ulcer haemorrhage * 0/107 (0.00%)
Pyrexia * 1/107 (0.93%) | Entailment |
Patients with cytologically confirmed, metastatic, early stage invasive breast cancer with an Allred score of 3 are eligible for the primary trial. | Inclusion Criteria:
Patients must have histologically or cytologically confirmed early stage, ER-positive (Allred score 3), invasive breast cancer that is not either locally advanced by criteria other than size or inflammatory, and is not metastatic. - Patients must be candidates for surgical removal of the tumor by lumpectomy or mastectomy. | Contradiction |
the primary trial administers the placebo and Urea/Lactic Acid Cream in the same frequency and on the same areas of the skin. | INTERVENTION 1:
Urea/Lactic Acid Cream
Patients receive topical urea/lactic acid-based cream applied to palms and soles twice daily.
INTERVENTION 2:
Placebo Cream
Patients receive placebo cream applied to palms and soles twice daily. | Entailment |
In order to participate in the primary trial, participants must be aware of where they are, and what day it is. | Inclusion Criteria:
Cognitively oriented to time, place, and person (determined via nurse recruiter) | Entailment |
There was a dental adverse event 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%) | Entailment |
Neither the primary trial or the secondary trial require participants to practice yoga while Wearing a Fitbit activity monitoring device. | INTERVENTION 1:
Group I (SparkPeople Program)
Participants receive training on how to use the SparkPeople website, self-monitor their diet using the SparkPeople tool, and to self-monitor their activity daily using the Fitbit monitoring device.
Participants receive weekly motivational reminders to log into the website for 3 months via email, text, or phone, based on patient preference (active phase). Participants then enter the maintenance phase for 3 months without reminders.
Behavioral Dietary Intervention: Use SparkPeople web-based program
Exercise Intervention: Use Fitbit monitor and SparkPeople web-based program
Activity Monitoring Device: Wear Fitbit activity monitoring device
INTERVENTION 2:
Group II (Wait List)
Participants receive the weight loss handout and a Fitbit activity monitor. After 6 months, participants receive the SparkPeople treatment.
Exercise Intervention: Use Fitbit monitor
Activity Monitoring Device: Wear Fitbit activity monitoring device
INTERVENTION 1:
Arm 1: Yoga Intervention
Yoga Intervention
Yoga: Yoga sessions
INTERVENTION 2:
Arm 2: Educational Wellness Group
Educational Wellness Group
Education: Educational Wellness Group | Entailment |
Patients in the primary trial receive an Infusion of Perflutren Lipid Microspheres, whereas in the secondary trial subjects are implanted with a Meso BioMatrix Acellular Peritoneum Matrix. | INTERVENTION 1:
Definity Infusion
Infusion of Definity (Perflutren Lipid Microspheres)
Definity infusion: 3 ml of Perflutren Lipid Microspheres (Definity) mixed in 50 ml of saline is infused at a rate of approximately 4ml/min
INTERVENTION 1:
Meso BioMatrix Acellular Peritoneum Matrix
All subjects had the Meso BioMatrix Acellular Peritoneum Matrix implanted along with a tissue expander during the first stage of breast reconstruction. After tissue expansion, the tissue expander was replaced with a breast implant during the second stage of reconstruction. | Entailment |
Cohort 1 of the primary trial recieves less than 60% of cohort 2's dose of LA-EP2006. | INTERVENTION 1:
Neratinib 40 mg
Neratinb 40 mg qd
INTERVENTION 2:
Neratinib 80 mg
Neratinib 80 mg qd | Entailment |
There were 0 observed cases of Tibia or Fibula fractures in the primary trial or the secondary trial. | Adverse Events 1:
Total: 16/149 (10.74%)
Anaemia 0/149 (0.00%)
Febrile neutropenia 7/149 (4.70%)
Neutropenia 1/149 (0.67%)
Pancytopenia 1/149 (0.67%)
Atrial fibrillation 2/149 (1.34%)
Cardiac failure congestive 0/149 (0.00%)
Abdominal pain 0/149 (0.00%)
Diarrhoea 2/149 (1.34%)
Dyspepsia 0/149 (0.00%)
Gastritis haemorrhagic 0/149 (0.00%)
Nausea 2/149 (1.34%)
Adverse Events 2:
Total: 20/151 (13.25%)
Anaemia 1/151 (0.66%)
Febrile neutropenia 4/151 (2.65%)
Neutropenia 2/151 (1.32%)
Pancytopenia 0/151 (0.00%)
Atrial fibrillation 0/151 (0.00%)
Cardiac failure congestive 1/151 (0.66%)
Abdominal pain 1/151 (0.66%)
Diarrhoea 3/151 (1.99%)
Dyspepsia 1/151 (0.66%)
Gastritis haemorrhagic 1/151 (0.66%)
Nausea 1/151 (0.66%)
Adverse Events 1:
Total: 5/95 (5.26%)
Febrile neutropenia 0/95 (0.00%)
Neutropenia 0/95 (0.00%)
Atrial fibrillation 0/95 (0.00%)
Pleuropericarditis 0/95 (0.00%)
Vomiting 0/95 (0.00%)
Pryexia 0/95 (0.00%)
Anaphylactic shock 1/95 (1.05%)
Gastroenteritis 0/95 (0.00%)
Fibula fracture 1/95 (1.05%)
Tibia fracture 1/95 (1.05%)
Intervertebral disc protrusion 0/95 (0.00%)
Adverse Events 2:
Total: 3/20 (15.00%)
Febrile neutropenia 0/20 (0.00%)
Neutropenia 0/20 (0.00%)
Atrial fibrillation 1/20 (5.00%)
Pleuropericarditis 1/20 (5.00%)
Vomiting 0/20 (0.00%)
Pryexia 0/20 (0.00%)
Anaphylactic shock 0/20 (0.00%)
Gastroenteritis 1/20 (5.00%)
Fibula fracture 0/20 (0.00%)
Tibia fracture 0/20 (0.00%)
Intervertebral disc protrusion 1/20 (5.00%) | Contradiction |
In order to be eligible for the primary trial, patients must not have prior radiation, anthracycline or systemic anticancer therapy , and must have T1-4, N1 and M1 bilateral breast cancer. | Exclusion Criteria:
Prior systemic anticancer therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
Prior anthracycline therapy or taxoids (paclitaxel, docetaxel) for any malignancy.
Prior radiation therapy for breast cancer.
Any T4 or N1-3 or M1 breast cancer. | Contradiction |
In total Over 82% patient in the primary trial achieve Recurrence-free Survival after 5 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% | Entailment |
INR of 1.35 is enough for participation in the primary trial and the secondary trial. | Inclusion Criteria:
International normalized ratio (INR) <=1.5 or prothrombin time (PT)/partial
Inclusion Criteria:
Female subjects participating in FMSU004A protocol with known clinical status
Exclusion Criteria:
Subjects with unknown clinical status not participating in FMSU004A protocol. | Contradiction |
One patient in cohort 2 of the primary trial crashed their motorbike. | Adverse Events 2:
Total: 8/537 (1.49%)
Hypertension 1/537 (0.19%)
Acoustic Neuroma 0/537 (0.00%)
Diarrhea 1/537 (0.19%)
Colitis 0/537 (0.00%)
Elevated ALT or AST enzyme 0/537 (0.00%)
Diagnosis of Uterine Cancer 2/537 (0.37%)
Motorcycle accident 1/537 (0.19%)
Fall 1/537 (0.19%)
Surgery 2/537 (0.37%) | Entailment |
There was over 10 more cases of adverse events in cohort 2 than in cohort 1 of the primary trial. | Adverse Events 1:
Total: 2/15 (13.33%)
Adverse Events 2:
Total: 11/35 (31.43%) | Contradiction |
A higher percentage of cohort 1 of the primary trial showed signs of fever, compared to cohort 2. | Adverse Events 1:
Fever * 2/41 (4.88%)
Adverse Events 2:
Fever * 0/5 (0.00%) | Entailment |
59% of Arm A of the primary trial achieved a best overall response, classified as a complete or partial (confirmed) tumor response or stable disease for at least 6 months. | Outcome Measurement:
Clinical Benefit Response (Independent Reviewer-assessed)
CBR is defined as the percentage of participants receiving at least one dose of study medication who achieved a best overall response classified as a complete or partial (confirmed) tumor response or stable disease for at least 6 months (24 weeks). A "complete response" is defined as the disappearance of all target or non-target lesions, "partial response" and "disease progression" as at least a 30% decrease and at least a 20% increase, respectively, in the sum of the longest diameter of target lesions, and "stable disease" as neither "partial response" nor "disease progression."
Time frame: Baseline, every 6 weeks until Week 24 and then every 12 weeks until disease progression (up to Week 119)
Results 1:
Arm/Group Title: Lapatinib 1250 mg and Capecitabine 2000 mg/m^2
Arm/Group Description: Participants took lapatinib and capecitabine. Lapatinib was orally administered at 1250 milligrams (mg) once daily. Capecitabine was orally administered at 1000 mg per square meter (mg/m^2) twice daily on the first day through the fourteenth day of each 21-day cycle.
Overall Number of Participants Analyzed: 51
Measure Type: Number
Unit of Measure: percentage of participants 59 | Entailment |
There is the same number of cases of Diplopia in the primary trial as anemia in the secondary trial. | Adverse Events 1:
Total: 1/6 (16.67%)
Angina pectoris 0/6 (0.00%)
Pericardial effusion 0/6 (0.00%)
Diplopia 0/6 (0.00%)
Abdominal pain 0/6 (0.00%)
Colitis 0/6 (0.00%)
Gastritis 0/6 (0.00%)
Nausea 0/6 (0.00%)
Vomiting 0/6 (0.00%)
Fatigue 0/6 (0.00%)
General physical health deterioration 0/6 (0.00%)
Generalised oedema 0/6 (0.00%)
Hepatic failure [1]0/6 (0.00%)
Adverse Events 2:
Total: 2/6 (33.33%)
Angina pectoris 0/6 (0.00%)
Pericardial effusion 0/6 (0.00%)
Diplopia 0/6 (0.00%)
Abdominal pain 0/6 (0.00%)
Colitis 0/6 (0.00%)
Gastritis 0/6 (0.00%)
Nausea 0/6 (0.00%)
Vomiting 0/6 (0.00%)
Fatigue 0/6 (0.00%)
General physical health deterioration 0/6 (0.00%)
Generalised oedema 0/6 (0.00%)
Hepatic failure [1]0/6 (0.00%)
Adverse Events 1:
Total: 0/2 (0.00%)
ANAEMIA 0/2 (0.00%)
FEBRILE NEUTROPENIA 0/2 (0.00%)
LYMPHADENOPATHY 0/2 (0.00%)
NEUTROPENIA 0/2 (0.00%)
PANCYTOPENIA 0/2 (0.00%)
THROMBOCYTOPENIA 0/2 (0.00%)
ATRIAL FIBRILLATION 0/2 (0.00%)
CARDIAC TAMPONADE 0/2 (0.00%)
PERICARDIAL EFFUSION 0/2 (0.00%)
TACHYCARDIA 0/2 (0.00%)
ABDOMINAL PAIN 0/2 (0.00%)
ABDOMINAL PAIN UPPER 0/2 (0.00%)
Adverse Events 2:
Total: 0/1 (0.00%)
ANAEMIA 0/1 (0.00%)
FEBRILE NEUTROPENIA 0/1 (0.00%)
LYMPHADENOPATHY 0/1 (0.00%)
NEUTROPENIA 0/1 (0.00%)
PANCYTOPENIA 0/1 (0.00%)
THROMBOCYTOPENIA 0/1 (0.00%)
ATRIAL FIBRILLATION 0/1 (0.00%)
CARDIAC TAMPONADE 0/1 (0.00%)
PERICARDIAL EFFUSION 0/1 (0.00%)
TACHYCARDIA 0/1 (0.00%)
ABDOMINAL PAIN 0/1 (0.00%)
ABDOMINAL PAIN UPPER 0/1 (0.00%) | Entailment |
the primary trial studies the effects of CTX/IMQ/RT and Epothilone on Central Nervous System (CNS) Progression-free Survival(PFS), 9 weeks after the start of treatment. | Outcome Measurement:
Systemic Tumor Response Rates (Complete Response+Partial Response)
The systemic tumor response refers to the response at the time of best overall response. The response criteria are specially adapted from Response Evaluation Criteria in Solid Tumor for Immunotherapies (Wolchok, et al., 2009).
Time frame: 9 weeks from the start of the treatment of RT | Contradiction |
Patients diagnosed with intradural tumors are excluded from the primary trial. | Exclusion Criteria:
No metastatic disease to the Central Nervous System | Entailment |
the primary trial participants will receive either Lapatinib, WBRT or Herceptin. | INTERVENTION 1:
Lapatinib,Whole Brain Radiation,Herceptin
Lapatinib before and during Whole Brain Radiation Therapy (WBRT), then Herceptin 4mg/kg IV weekly | Contradiction |
There was less than a 5% difference in the results from the 9 mg and 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 | Entailment |
the primary trial has a topical intervention, whereas the secondary trial has both oral and IV interventions. | INTERVENTION 1:
Mometasone
Patients apply 2.5 mL mometasone furoate cream once daily to the treatment area (breast or chest wall) for the duration of planned radiotherapy.
INTERVENTION 2:
Placebo
Patients apply 2.5 mL of an identical-appearing placebo cream to the treatment area as in arm A.
INTERVENTION 1:
Afatinib Monotherapy
Patient received Afatinib monotherapy orally once daily at a dose of 40 milligram (mg) film-coated tablets until progression of their disease, unacceptable adverse events or other reason necessitating withdrawal. Patients could have dose reduced if 40 mg was not tolerated.
INTERVENTION 2:
Afatinib and Paclitaxel or Vinorelbine Combination Therapy
Patient received Afatinib monotherapy orally once daily at a dose of 40 mg film-coated tablets until progression of their disease, unacceptable adverse events or other reason necessitating withdrawal (Patients could have dose reduced if 40 mg was not tolerated) and 80 mg/square meter (m2) Paclitaxel concentrate for intravenous infusion or 25 mg/m2 Vinorelbine concentrate for intravenous infusion once weekly starting after treatment failure on afatinib monotherapy | Entailment |
All patients in the Letrozole group of the primary trial had a decreased Bone Mineral Density of the Lumbar Spine after 3 years. | Outcome Measurement:
Percent Change From Baseline of Bone Mineral Density of the Lumbar Spine (L2-l4)
Lumbar spine (L2-L4) BMD measurements by dual energy X-ray absorptiometry (DXA) were performed after surgery and within 2 weeks prior to randomization and repeated every 6 months for the first 2 years and annually thereafter until 5 years after enrollment. The primary scanning site was the lumbar spine (L2 to L4) and the secondary scanning site was the total hip. All DXA scans were evaluated by a central reader.
Time frame: Baseline, 24 months
Results 1:
Arm/Group Title: Letrozole
Arm/Group Description: 2.5 mg once daily (q.d.)orally for 5 years
Overall Number of Participants Analyzed: 63
Median (Full Range)
Unit of Measure: Percent Change -4.63 (-14.21 to 4.32)
Results 2:
Arm/Group Title: Tam-Let
Arm/Group Description: 20 mg Tamoxifen once daily (q.d.) orally for 2 years followed by Letrozole 2.5 mg q.d. orally for 3 years.
Overall Number of Participants Analyzed: 68
Median (Full Range)
Unit of Measure: Percent Change 0.37 (-6.98 to 15.21) | Contradiction |