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enterocolitis was a common condition among participants in both the secondary trial and the primary trial. | Adverse Events 1:
Total: 20/167 (11.98%)
Cardiac failure acute 0/167 (0.00%)
Diarrhoea 5/167 (2.99%)
Colitis 2/167 (1.20%)
Enterocolitis 1/167 (0.60%)
Enterocolitis haemorrhagic 1/167 (0.60%)
Stomatitis 1/167 (0.60%)
Impaired healing 1/167 (0.60%)
Sudden death 1/167 (0.60%)
Postoperative wound infection 2/167 (1.20%)
Erysipelas 2/167 (1.20%)
Bacterial diarrhoea 1/167 (0.60%)
Adverse Events 2:
Total: 4/167 (2.40%)
Cardiac failure acute 1/167 (0.60%)
Diarrhoea 0/167 (0.00%)
Colitis 0/167 (0.00%)
Enterocolitis 0/167 (0.00%)
Enterocolitis haemorrhagic 0/167 (0.00%)
Stomatitis 0/167 (0.00%)
Impaired healing 0/167 (0.00%)
Sudden death 0/167 (0.00%)
Postoperative wound infection 1/167 (0.60%)
Erysipelas 0/167 (0.00%)
Bacterial diarrhoea 0/167 (0.00%)
Adverse Events 1:
Total: 112/458 (24.45%)
Febrile neutropenia 8/458 (1.75%)
Neutropenia 6/458 (1.31%)
Anaemia 3/458 (0.66%)
Thrombocytopenia 3/458 (0.66%)
Pancytopenia 2/458 (0.44%)
Myocardial infarction 0/458 (0.00%)
Pericardial effusion 0/458 (0.00%)
Tachycardia 0/458 (0.00%)
Acute myocardial infarction 1/458 (0.22%)
Atrial fibrillation 0/458 (0.00%)
Adverse Events 2:
Total: 39/221 (17.65%)
Febrile neutropenia 5/221 (2.26%)
Neutropenia 1/221 (0.45%)
Anaemia 2/221 (0.90%)
Thrombocytopenia 0/221 (0.00%)
Pancytopenia 0/221 (0.00%)
Myocardial infarction 2/221 (0.90%)
Pericardial effusion 2/221 (0.90%)
Tachycardia 2/221 (0.90%)
Acute myocardial infarction 0/221 (0.00%)
Atrial fibrillation 1/221 (0.45%) | Contradiction |
in the cohorts of the primary clinical trial, no incidents of death were reported. | Outcome Measurement:
Patients Event-free at 12 Months (Where Event = Death (From Any Cause), Disseminated Tumour Cells (DTC) Positive at 12 Months or Clinical Disease Recurrence)
Number of patients event-free
Time frame: 12 month period following randomisation
Results 1:
Arm/Group Title: Fulvestrant + Anastrozole
Arm/Group Description: fulvestrant 500 mg + anastrozole 1 mg
Overall Number of Participants Analyzed: 6
Measure Type: Number
Unit of Measure: Participants 6
Results 2:
Arm/Group Title: Anastrozole
Arm/Group Description: anastrozole 1 mg
Overall Number of Participants Analyzed: 7
Measure Type: Number
Unit of Measure: Participants 7 | Entailment |
patients with a predicted survival of at least one year are qualified to participate in the primary clinical trial | Inclusion criteria:
Female patients 18 years of age.
Written informed consent given.
Histologically confirmed Stage IV breast cancer with at least one bone metastasis radiologically confirmed.
Previous treatment with zoledronic acid every 3-4 weeks, for 9-12 infusions over no more than 15 months.
Eastern Cooperative Oncology Group (ECOG) performance status 2 .
Life expectancy 1 year.
Exclusion criteria:
More than 3 months since last infusion of Zoledronic Acid (Zometa®).
Treatments with other bisphosphonate than Zoledronic Acid (Zometa®) at any time prior to study entry.
Serum creatinine > 3 mg/dL (265 μmol/L) or calculated (Cockcroft-Gault formula) creatinine clearance (CLCr) < 30 mL/min CrCl = ({[140-age (years)] x weight(kg)}/ [72 x serum creatinine (mg/dL)])x 0.85
Corrected (adjusted for serum albumin) serum calcium < 8 mg/dl (2 mmol/L) or > 12 mg/dL ( 3.0 mmol/L).
Current active dental problem including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a recurrent or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
Recent (within 6 weeks) or planned dental or jaw surgery (e.g. extraction, implants).
Pregnant patients (with a positive pregnancy test prior to study entry) or lactating patients. Women of childbearing potential not using effective methods of birth control (e.g. abstinence, oral contraceptives or implants, IUD, vaginal diaphragm or sponge, or condom with spermicide).
History of non-compliance to medical regimens or potential unreliable behavior.
Known sensitivity to study drug(s) or class of study drug(s).
Patients with severe medical condition(s) that in the view of the investigator prohibits participation in the study
Use of any other investigational agent in the last 30 days. | Entailment |
dose limiting toxicities were suffered by 50% of cohort 2 patients in the primary clinical trial | Outcome Measurement:
Phase I: The Number of Dose Limiting Toxicities in AZD8931 in Combination With Weekly Paclitaxel
DLT is an AE or laboratory abnormality related to AZD8931, starting during the DLT evaluation period and meeting any of the following criteria (further detail in protocol): Symptomatic ocular surface lesion; CTCAE grade 4 haematological AE; CTCAE grade 3 of febrile neutropenia / neutropenia / thrombocytopenia / hyperkalaemia / hyperglycaemia / hypotension / urological toxicity / ILD / pneumonitis; QTcF interval > 500 msec, two ECGs 30 minutes apart; Symptomatic congestive cardiac failure and a drop in LVEF; Decrease in LVEF of 20% to below the LLN; CS rash remaining CTCAE grade 3 for 5 days despite optimal treatment; CTCAE grade 3 nausea, vomiting or diarrhoea, despite optimal therapy; Other CTCAE grade 3 toxicity which, in the opinion of the investigator, is CS and related to AZD8931; Delay to the administration of paclitaxel on D1 of Cycle 2 by 7 days. Patients could have more than one DLT.
Time frame: Weekly visits for routine safety monitoring from Day 1 to Day 28 for each participant
Results 1:
Arm/Group Title: AZD8931 160 mg bd
Arm/Group Description: Part A: AZD8931 160mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle
Overall Number of Participants Analyzed: 6
Measure Type: Number
Unit of Measure: Number of Dose Limiting Toxicities Total: 2
Eye disorders: Keratitis: 1
Eye disorders: Photophobia: 1
Gastrointestinal disorders: Diarrhoea: 1
Gastrointestinal disorders: Oesophagitis: 0
Infections and infestations: Rash pustular: 0
Results 2:
Arm/Group Title: AZD8931 120 mg bd
Arm/Group Description: Part A: AZD8931 120mg (bd) plus weekly paclitaxel of 90mg/m2 on days 1, 8 and 15 of each 28 day cycle
Overall Number of Participants Analyzed: 2
Measure Type: Number
Unit of Measure: Number of Dose Limiting Toxicities Total: 1
Eye disorders: Keratitis: 0
Eye disorders: Photophobia: 0
Gastrointestinal disorders: Diarrhoea: 1
Gastrointestinal disorders: Oesophagitis: 0
Infections and infestations: Rash pustular: 0 | Entailment |
only those diagnosed with her2-positive breast cancer can participate in the primary clinical trial | Inclusion Criteria:
Archival tumor samples must be obtained from primary and/or metastatic sites
Able to submit tumor tissue that is evaluable for programmed death- ligand 1 (PD-L1) expression
HER-2 positive BC as defined by an immunohistochemistry score of 3 or gene amplified by in-situ hybridization as defined by a ratio of greater than or equal to (>=) 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies
Histologically or cytologically confirmed invasive BC: incurable, unresectable, locally advanced BC previously treated with multimodality therapy or metastatic BC
Prior treatment for BC in the: adjuvant; unresectable locally advanced; or metastatic settings; which must include both, a taxane and trastuzumab (alone or in combination with another agent)
Progression must have occurred during or after most recent treatment for locally advanced/metastatic BC or within 6 months after completing adjuvant therapy
Participants must have measurable disease that is evaluable as per RECIST v1.1
Eastern Cooperative Oncology Group Performance Status of 0 or 1
Negative serum pregnancy test within 7 days of enrollment for pre-menopausal women and for women less than 12 months after the onset of menopause
Use of highly effective method of contraception as defined by the protocol
Exclusion Criteria:
Prior treatment with trastuzumab emtansine, cluster of differentiation 137 agonists, anti-programmed death-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
Receipt of any anti-cancer drug/biologic or investigational treatment within 21 days prior to Cycle 1 Day 1 except hormone therapy, which can be given up to 7 days prior to Cycle 1 Day 1; recovery of treatment related toxicity consistent with other eligibility criteria
Radiation therapy within 2 weeks prior to Cycle 1, Day 1
History of exposure to the cumulative doses of anthracyclines
History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or participants who have undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to be at low risk for recurrence
Cardiopulmonary dysfunction, symptomatic pleural effusion, pericardial effusion, or ascites
Participants with severe infection within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
Current severe, uncontrolled systemic disease
Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, sclerosis cholangitis or active infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus
Need for current chronic corticosteroid therapy (>=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids)
Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for greater than (>) 2 weeks prior to randomization
Participants with known central nervous system disease
Leptomeningeal disease
History of autoimmune disease
Prior allogeneic stem cell or solid organ transplantation
Active tuberculosis
Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study
Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization
Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial
Participants who are breastfeeding, or intending to become pregnant during the study | Entailment |
a malignant brain tumour diagnosis qualifies a patient for inclusion in the primary clinical trial | Inclusion Criteria:
Must have received prior chemotherapy with Taxol (paclitaxel) or Taxotere (docetaxel).
Less than 3 different chemotherapy treatments for metastatic disease.
Prior treatment with hormonal and/or radiation therapy.
Must have disease that can be measured.
Must be able to take care of self needs for example personal hygiene
Exclusion Criteria:
Must not be pregnant or breast-feeding.
Cancer that has spread to the brain.
Treatment with Gemcitabine or Pemetrexed
Unable to take folic acid or Vitamin B12
Treatment for another cancer within the last 5 years | Contradiction |
most participants in the first and second cohort of the primary clinical trial failed to attain 5 years of disease-free survival. | Outcome Measurement:
Disease-free Survival: Any Recurrence, Contralateral Breast Cancer, Second Primary Cancer, Death From Any Cause Prior to Recurrence or Second Primary Cancer
The percentage of patients alive and cancer-free.
Time frame: 5 years
Results 1:
Arm/Group Title: Group 1: TAC X 6
Arm/Group Description: Doxorubicin, cyclophosphamide, and docetaxel.
Cyclophosphamide: Group 1: cyclophosphamide 500 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: cyclophosphamide 600 mg/m2 IV every 14 days for 4 cycles
Docetaxel: 75 mg/m2 IV every 21 days for 6 cycles
Doxorubicin: Group 1: 50 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: 60 mg/m2 IV every 14 days for 4 cycles
Overall Number of Participants Analyzed: 1610
Measure Type: Number
Unit of Measure: percentage of patients 80.1 (78.0 to 82.0)
Results 2:
Arm/Group Title: Group 2: AC X 4 Then P X 4
Arm/Group Description: Doxorubicin, cyclophosphamide, and paclitaxel
Cyclophosphamide: Group 1: cyclophosphamide 500 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: cyclophosphamide 600 mg/m2 IV every 14 days for 4 cycles
Paclitaxel: 175 mg/m2 IV every 14 days for 4 cycles
Doxorubicin: Group 1: 50 mg/m2 IV every 21 days for 6 cycles
Group 2 and Group 3: 60 mg/m2 IV every 14 days for 4 cycles
Overall Number of Participants Analyzed: 1618
Measure Type: Number
Unit of Measure: percentage of patients 82.2 (80.2 to 84.0) | Contradiction |
everolimus is given intramuscularly (to the deltoid) and fulvestrant orally in the context of the primary clinical trial. | INTERVENTION 1:
Fulvestrant + Everolimus
Fulvestrant + Everolimus
Fulvestrant was administered intramuscularly (in the gluteus maximus) in a loading dose schedule as follows: 500 mg in two divided doses-one on each side on day 1, then 250 mg on day 14, and then 250 mg on day 28 and every 4 weeks ± 3 days thereafter. Everolimus was administered initially at a dose of 5 mg daily in the first 5-patient cohort for the first month of treatment and then increased to 10 mg PO daily after that. | Contradiction |
if an individual is qualified to participate in the secondary clinical trial, they will also be qualified for the primary clinical trial | Inclusion Criteria:
Female or male patients with diagnosis of invasive adenocarcinoma of the breast confirmed at MSKCC.
For the phase I portion, patients with any ER/PR/HER2 disease status, no longer eligible for hormonal therapy or HER2-targeted therapy, will be eligible.
For the phase II portion, there needs to be documentation of negative HER2 (IHC 0-1+ or FISH/CISH negative) status. Patients with any ER/PR disease status are eligible.
A paraffin-embedded tissue block or unstained slides from prior surgery must be available.
Evidence of recurrent or progressive locally advanced or metastatic breast cancer.
Presence of:
For the phase I portion: at least one evaluable or measurable metastatic lesion ,
For the phase II portion: at least one measurable metastatic lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Ascites, pleural effusion, and bone metastases are not considered measurable. Minimum indicator lesion size: > or = to 10 mm measured by spiral CT or > or = to 20 mm measured by conventional techniques.
Prior therapies:
For the phase I portion: Any number of prior endocrine or biologic therapies is permitted . In addition, patients may be untreated in the metastatic setting or have received any number of prior cytotoxic regimens.
For the phase II portion: 0-2 prior therapies for metastatic disease are allowed.
Prior taxane therapy, either in the adjuvant or in the metastatic setting, either deliver weekly, q 2 weeks or q 3 weeks, will be permitted. Prior therapy with bevacizumab will be allowed. All previous chemotherapy, radiotherapy and intravenous biphosphonates must have been discontinued at least 3 weeks prior to study entry, 3 weeks also for trastuzumab and bevacizumab. All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to NCI CTC (Version 3) Grade 1.
Endocrine therapy with an aromatase inhibitor, SERM (ie, tamoxifen) or fulvestrant is permitted, however it must be discontinued before enrolling in the study.
ECOG performance status of 0 or 1.
Age > or = to 18 years old. Adequate Organ Function
Total bilirubin 1.5 times the institutional Upper Limit of Normal (ULN)
Hepatic enzymes (AST, ALT ) 2.5 times the institutional ULN
Serum Na, K+, Mg2+, Phosphate and Ca2+ Lower Limit of Normal (LLN)
Serum Creatinine 1.5 time the institutional ULN
Neutrophil count, Platelets, both Grade 0-1
PT (INR) and PTT Grade 0-1, except for patients on Coumadin or low molecular weight heparin
Ability to take oral medication (dasatinib must be swallowed whole)
Concomitant Medications:
Patient agrees to discontinue St. Johns Wort while receiving dasatinib therapy
Patient agrees that IV biphosphonates will be withheld for the first 8 weeks of dasatinib therapy due to risk of hypocalcemia. Concomitant Medications, any of the following should be considered for exclusion:
Patient agrees to discontinue QT-prolonging agents strongly associated with Torsades de Pointes including: (patients must discontinue drug 7 days prior to starting dasatinib) such as:
quinidine, procainamide, disopyramide
amiodarone, sotalol, ibutilide, dofetilide
erythromycin, clarithromycin
chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide
cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine.
The concomitant use of H2 blockers or proton pump inhibitors with dasatinib is not recommended. The use of antacids should be considered in place of H2 blockers or proton pump inhibitors in patients receiving dasatinib therapy. If antacid therapy is needed, the antacid dose should be administered at least 2 hours prior to or 2 hours after the dose of dasatinib.
Patient may not be receiving any potent CYP3A4 inhibitors. These are prohibited (patients must discontinue drug 7 days prior to starting dasatinib) and include:
itraconazole, ketoconazole, miconazole, coriconazole
amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir
ciprofloxacin, clarithromycin, diclofenac, doxycycline, enoxacin, imatinib, isoniazid
ketamine, nefazodone, nicardipine, propofol, quinidine, telithromycin
Women of childbearing potential (WOCBP) must have:
A negative serum or urine pregnancy test within 72 hours prior to the start of study drug administration
Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 4 weeks after study drug is stopped
Pregnant or nursing women may not participate. Patients of reproductive potential may not participate unless they have agreed to use an effective method of contraception and to continue contraception for 30 days from the date of the last study drug administration. Postmenopausal woman must be amenorrheic for at least 12 months to be considered of non-childbearing potential.
Signed written informed consent including a HIPAA form according to institutional guidelines.
Exclusion Criteria:
Life expectancy < 3 months.
Prior severe allergic reaction to paclitaxel therapy.
Presence of new or recurrent pleural effusion which is symptomatic and/or requiring medical intervention (NCI CTC Grade 2, 3 or 4).
Completion of previous chemotherapy regimen < 3 weeks prior to the start of study treatment.
Prior hormonal therapy must be discontinued prior to treatment start. Biologic therapy (eg, bevacizumab, trastuzumab) for the treatment of metastatic disease must be discontinued > or = to 3 weeks from the start of protocol treatment.
Concurrent medical condition which may increase the risk of toxicity.
Patients may not have any clinically significant cardiovascular disease including the following:
myocardial infarction or ventricular tachyarrhythmia within 6 months
prolonged QTc >480 msec (Fridericia correction)
ejection fraction less than institutional normal
major conduction abnormality (unless a cardiac pacemaker is present)
Patients with any cardiopulmonary symptoms of unknown cause (e.g. shortness of breath, chest pain, etc.) should be evaluated by a baseline echocardiogram with or without stress test as needed in addition to electrocardiogram (EKG) to rule out QTc prolongation. The patient may be referred to a cardiologist at the discretion of the principal investigator. Patients with underlying cardiopulmonary dysfunction should be excluded from the study.
Subjects with hypokalemia or hypomagnesemia if it cannot be corrected prior to dasatinib administration
History of significant bleeding disorder unrelated to cancer, including:
Diagnosed congenital bleeding disorders (e.g., von Willebrand's disease)
Diagnosed acquired bleeding disorder within one year (e.g., acquired antifactor VIII antibodies)
Ongoing or recent ( 3 months) significant gastrointestinal bleeding Other medical condition which in the opinion of the Investigator might confer an unacceptable increase in risk.
Patients with symptomatic CNS metastases that remain untreated by radiation therapy are excluded from this trial. The presence of asymptomatic brain metastases or brain metastases that have been previously irradiated are not grounds for trial exclusion.
History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
Presence of uncontrolled gastrointestinal malabsorption syndrome.
Unwillingness to give written informed consent or unwillingness to participate or inability to comply with the protocol for the duration of the study. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures are necessary for participation in this clinical trial.
Concurrent radiotherapy is not permitted for disease progression on treatment on protocol, but might allowed for pre-existing non-target lesions with approval from the principal investigator of the trial.
Patients with > Grade 1 neuropathy will be excluded form this trial.
Inclusion criteria:
Signed Informed Consent
ErbB2(HER2)overexpressing breast cancer.
Brain lesion(s) which are progressing.
Prior treatment of brain metastases with Whole Brain Radiotherapy (WBR)and/or Stereotactic Radiosurgery (SRS).
Prior treatment with trastuzumab (Herceptin), either alone or in combination with chemotherapy.
Cardiac ejection fraction(LVEF)within the institutional range of normal as measured by Echocardiogram.
Able to swallow an oral medication.
Adequate kidney and liver function.
Adequate bone marrow function.
Exclusion criteria:
Pregnant or lactating females.
Conditions that would effect the absorption of an oral drug.
History of immediate or delayed hypersensitivity reaction to gadolinium contrast agents.
Pre-existing severe cerebral vascular disease, such as stroke involving a major vessel.
Serious medical or psychiatric disorder that would interfere with the patient's safety or informed consent. | Contradiction |
absence of radiographically confirmed metastases to the brain is a prerequisite for eligibility in the primary clinical trial. | DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed breast cancer with radiographically confirmed metastases to the brain
Extracranial metastases allowed
Must have demonstrated progression of brain metastases after prior treatment for brain metastases, including any of the following:
External beam radiotherapy
Brachytherapy
Stereotactic radiosurgery
Surgery
Chemotherapy
Treatments with investigational drugs, biologics, or devices
Disease progression in the CNS must meet 1 of the following criteria:
New lesions in the CNS on an imaging study (contrast-enhanced CT scan or MRI)
Progressive lesions on an imaging study (contrast-enhanced CT scan or MRI)
New or progressive lesions that do not meet measurable disease definition allowed
Leptomeningeal disease allowed if concurrent progression or parenchymal brain metastases
Not a candidate for surgical resection and/or further stereotactic radiosurgery
Hormone receptor status not specified
PATIENT CHARACTERISTICS:
Menopausal status not specified
ECOG performance status 0-2
Life expectancy 1 month
Hemoglobin 10 g/dL (transfusion allowed)
ANC 1,500/mm³
Granulocyte count 1,500/mm³
Platelet count 100,000/mm³
Creatinine 1.5 mg/dL
Total bilirubin 1.5 times upper limit of normal (ULN)
AST and ALT 3 times ULN
Must be able to swallow and retain oral medications
No other active malignancy except for any of the following:
Curatively treated basal or squamous cell carcinoma of the skin
Carcinoma in situ of the cervix
Other malignancies considered disease-free
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of immediate or delayed-type hypersensitivity reaction to gadolinium contrast agents or other contraindication to gadolinium contrast
No other known contraindication to MRI including, but not limited to, any of the following:
Cardiac pacemaker
Implanted cardiac defibrillator
Brain aneurysm clips
Cochlear implant
Ocular foreign body
Shrapnel
No active or uncontrolled infection
PRIOR CONCURRENT THERAPY:
See Disease Characteristics
Recovered from the side effects of prior chemotherapy, surgery, or radiotherapy for extracranial disease or brain metastases
Concurrent trastuzumab, bisphosphonate, and/or corticosteroid therapy allowed
At least 1 week since prior or on current stable dose of corticosteroid therapy
Patients on an enzyme-inducing anti-epileptic agent (EIAE) or valproic acid are eligible if they are switched to an alternate non-EIAE medication
Concurrent coumadin allowed
No prophylactic use of filgrastim (G-CSF) during first course of treatment | Contradiction |
the incidence of recorded musculoskeletal adverse events was distributed evenly between the two cohorts of the secondary clinical trial | Adverse Events 1:
Total: 0/34 (0.00%)
Adverse Events 1:
Total: 6/62 (9.68%)
Musculoskeletal * 1/62 (1.61%)
Mood Alteration: Depression * 1/62 (1.61%)
renal - Other * 1/62 (1.61%)
Obstruction, GU: Uterus * 1/62 (1.61%)
Sexual * 0/62 (0.00%)
Pulmonary/Upper Respiratory: Dyspnea * 1/62 (1.61%)
Ulceration * 1/62 (1.61%)
Adverse Events 2:
Total: 1/64 (1.56%)
Musculoskeletal * 0/64 (0.00%)
Mood Alteration: Depression * 0/64 (0.00%)
renal - Other * 0/64 (0.00%)
Obstruction, GU: Uterus * 0/64 (0.00%)
Sexual * 1/64 (1.56%)
Pulmonary/Upper Respiratory: Dyspnea * 0/64 (0.00%)
Ulceration * 0/64 (0.00%) | Contradiction |
the only case of congestive heart failure in the primary clinical trial emerged in cohort 2. | Adverse Events 1:
Total: 1/35 (2.86%)
congestive heart failure *1/35 (2.86%)
Adverse Events 2:
Total: 0/40 (0.00%)
congestive heart failure *0/40 (0.00%) | Contradiction |
vaginal cream dosage form is a cream intended for administration in or around the vagina. The the primary trial intervention involves one drug taken orally and the secondary trial intervention is based on a medical procedure. | INTERVENTION 1:
Letrozole
Participants received 2.5 milligram (mg) of Letrozole tablets orally once daily (QD) for a period of 24 weeks.
INTERVENTION 1:
Sentinel Lymph Node Biopsy
[Not Specified] | Contradiction |
participants who wish to join the primary clinical trial should have a confirmed tnbc status and an lvef rate of 50% or greater | Inclusion Criteria:
For women of childbearing potential and men with partners of childbearing potential, agreement to use a highly-effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by the participant and/or partner
Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection; participants with measurable and/or non-measurable disease are eligible
Known and documented HER2-positive
Known and documented LVEF of at least 50 percent (%)
Adequate organ function
A negative serum beta-human chorionic gonadotropin (beta-HCG) test for women of childbearing potential (premenopausal, or less than [<] 12 months of amenorrhea post-menopause, and women who have not undergone surgical sterilization [absence of ovaries and/or uterus]) within 7 days prior to the first dose of study treatment with the result available prior to first dosing
Exclusion Criteria:
Previous systemic non-hormonal anti-cancer therapy for the metastatic or locally recurrent disease
Pregnant or lactating women
Current clinical or radiographic evidence of central nervous system (CNS) metastases
Disease progression while receiving or within 12 months of completion of trastuzumab and/or lapatinib treatment in the adjuvant or neo-adjuvant setting
History of LVEF decline to below 50% during or after prior trastuzumab adjuvant or neo-adjuvant therapy | Contradiction |
posterior tibial artery branch is any artery arising from the posterior tibial artery. there is a minimal difference between the results from the two the primary trial cohorts. | Outcome Measurement:
Event-free Survival
Event free survival, the primary endpoint of this study, is defined as the time from randomization to the time of documented locoregional or distant recurrence, new primary breast cancer, or death from any cause.
Time frame: 5 years
Results 1:
Arm/Group Title: Exemestane
Arm/Group Description: Patients receive oral exemestane (25 mg) once daily for 5 years.
exemestane: Given orally
Overall Number of Participants Analyzed: 3789
Measure Type: Number
Unit of Measure: percentage of participants 88 (87 to 89)
Results 2:
Arm/Group Title: Anastrozole
Arm/Group Description: Patients receive oral anastrozole (1 mg) once daily for 5 years.
anastrozole: Given orally
Overall Number of Participants Analyzed: 3787
Measure Type: Number
Unit of Measure: percentage of participants 89 (88 to 90) | Entailment |
to be accepted into the primary clinical trial, patients need to have a tangible carcinoma | Inclusion Criteria Phase 1
Age greater than/equal to 18 years
Histologic diagnosis of palpable invasive breast cancer or ductal carcinoma in situ
Patient desire to undergo breast surgery
3. Patients will have provided informed consent to participate, documented by their signature on the study consent form 4. The cancer enhances on breast MRI imaging.
Inclusion Criteria Phase 2
Age greater than/equal to 18 years
Histologic diagnosis of invasive breast cancer or ductal carcinoma in situ
The tumor is visible and enhances on prone MRI and is >1 cm in greatest diameter.
. Determination by the surgeon that the neoplasm is non-palpable.A patient with a palpable hematoma from core biopsy, but a non-palpable neoplasm, will be eligible for study
Patient desire to undergo breast conserving surgery
Patients will have provided informed consent to participate, documented by their signature on the study consent form.The process of informed consent will be documented in the medical record and a copy of the signed consent form will be given to the patient.
Exclusion Criteria (Phases 1 and 2)
Absolute contraindication to MRI, including presence of implanted electrical device (pacemaker or neurostimulator), aneurysm clip or metallic foreign body in or near eyes
Severe claustrophobia
Contraindication to use of gadolinium based intravenous contrast, including life threatening allergy or compromised renal function (creatinine > 2.0)
History of median sternotomy
Pregnancy (Patient attestation that they are not pregnant will be acceptable, as per standard, as per standard policy for MRIs at DHMC).
Multicentric breast cancer, defined as two or more tumors in different quadrants of the breast. An eligibility worksheet will be completed for each patient prior to enrollment and will be signed and dated by the surgeon investigator | Entailment |
kbtbd4 small in-frame insertion mutation is an in-frame nucleotide insertion affecting six codons or less in the kbtbd4 gene. there is a 13.2% difference between the results from the two the primary trial cohorts. | Outcome Measurement:
Event-free Survival
Event free survival, the primary endpoint of this study, is defined as the time from randomization to the time of documented locoregional or distant recurrence, new primary breast cancer, or death from any cause.
Time frame: 5 years
Results 1:
Arm/Group Title: Exemestane
Arm/Group Description: Patients receive oral exemestane (25 mg) once daily for 5 years.
exemestane: Given orally
Overall Number of Participants Analyzed: 3789
Measure Type: Number
Unit of Measure: percentage of participants 88 (87 to 89)
Results 2:
Arm/Group Title: Anastrozole
Arm/Group Description: Patients receive oral anastrozole (1 mg) once daily for 5 years.
anastrozole: Given orally
Overall Number of Participants Analyzed: 3787
Measure Type: Number
Unit of Measure: percentage of participants 89 (88 to 90) | Contradiction |
no diarrhea was identified among the patients of the secondary trial, whereas multiple instances were detected among the participants of the primary trial | Adverse Events 1:
Total: 59/373 (15.82%)
Neutropenia 14/373 (3.75%)
Febrile neutropenia 10/373 (2.68%)
Leukopenia 1/373 (0.27%)
Anaemia 2/373 (0.54%)
Lymphadenopathy 0/373 (0.00%)
cardiac failure 2/373 (0.54%)
Atrial fibrillation 1/373 (0.27%)
Pericardial effusion 2/373 (0.54%)
Cardiac failure congestive 1/373 (0.27%)
Cardiomyopathy 0/373 (0.00%)
Adverse Events 2:
Total: 69/377 (18.30%)
Neutropenia 17/377 (4.51%)
Febrile neutropenia 10/377 (2.65%)
Leukopenia 4/377 (1.06%)
Anaemia 2/377 (0.53%)
Lymphadenopathy 1/377 (0.27%)
cardiac failure 1/377 (0.27%)
Atrial fibrillation 1/377 (0.27%)
Pericardial effusion 0/377 (0.00%)
Cardiac failure congestive 0/377 (0.00%)
Cardiomyopathy 1/377 (0.27%)
Adverse Events 1:
Total: 0/92 (0.00%)
Diarrhea 0/92 (0.00%)
Adverse Events 2:
Total: 1/93 (1.08%)
Diarrhea 1/93 (1.08%) | Contradiction |
22q12.2 is a chromosome band present on 22q Most patients in the primary trial experienced a grade 1 adverse events, the least common severity was grade 4. | Outcome Measurement:
Severity of Adverse Events
Adverse events (AEs) grading was completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03.
Time frame: From cycle 1 up to approximately 3 years
Results 1:
Arm/Group Title: Trastuzumab Emtansine
Arm/Group Description: 3.6 mg/kg of trastuzumab emtansine was administered to participants intravenously (IV) over 30-90 minutes on day 1 of 21 day cycle and was repeated every 3 weeks.
Overall Number of Participants Analyzed: 70
Measure Type: Count of Participants
Unit of Measure: Participants Grade 1: 53 75.7%
Grade 2: 40 57.1%
Grade 3: 18 25.7%
Grade 4: 2 2.9%
Grade 5: 12 17.1% | Entailment |
the outcome measurement of the primary clinical trial is the rate of patients' response to the treatment | Outcome Measurement:
Progression-free Survival (PFS) and to Evaluate Safety of the Trastuzumab, Bevacizumab and Docetaxel Regimen.
The trial was designed as a single-stage phase II rather then usual two-stage design because of the progression free survival (PFS) primary endpoint, as it is impractical to wait to assess PFS for patients in the first stage. We will consider a PFS of 50% at twelve months (median PFS of 12 months) or less uninteresting and a PFS of 70% at twelve months (median PFS of twenty months) worthy of pursuing the regimen in a future trials. The single-stage design is as follows: p0=0.50, p1=0.70, α=0.10, β= 0.10. This leads to a total sample size of 39 patients, 24 or higher of who are progression-free at 12 months.
Time frame: up to 3 years
Results 1:
Arm/Group Title: Trastuzumab, Bevacizumab, and Docetaxel
Arm/Group Description: Trastuzumab [6mg/kg], Bevacizumab [15mg/kg], and Docetaxel [75 mg/M ]
Overall Number of Participants Analyzed: 26
Median (95% Confidence Interval)
Unit of Measure: months 14.3 (9.3 to 35) | Contradiction |
occurrence of hot flashes is not a prerequisite for patient participation in the primary or secondary clinical trials. | DISEASE CHARACTERISTICS:
Women with a history of breast cancer (currently without malignant disease)
Bothersome hot flashes (defined by their occurrence 28 times per week and of sufficient severity to make the patient desire therapeutic intervention)
Presence of hot flashes for 30 days prior to study registration
Willingness to provide the biologic specimens as required by the protocol
Hormone receptor status not specified
PATIENT CHARACTERISTICS:
Women who are postmenopausal as defined by absence of a period in the past 12 months or bilateral oophorectomy
Women with at least one ovary but without a uterus should be deemed postmenopausal by either age over 55 or a combination of estrogen within a postmenopausal range (per local lab) and FSH over 40 mIU/mL
No women of childbearing potential or who are premenopausal
Creatinine clearance > 30 mL/min
Ability to complete questionnaire(s) by themselves or with assistance
ECOG performance status 0 or 1
No history of allergic or other adverse reaction to magnesium
No diabetes
No patients with conditions that are implicated in decreased absorption of magnesium (e.g., Crohn disease, ETOH abuse)
No patients who have diarrhea where magnesium might make it worse (per provider discretion)
PRIOR CONCURRENT THERAPY:
None of the following current ( 28 days prior to registration) or planned therapies (tamoxifen, raloxifene, or aromatase inhibitors are allowed, but the patient must have been on a constant dose for 28 days and must not be expected to stop the medication during the study period):
Antineoplastic chemotherapy (trastuzumab or lapatinib are allowed)
Androgens
Estrogens (any delivery route)
Progestational agents
No prior use of magnesium for hot flashes
No current or planned use of gabapentin (for any reasons) or antidepressants (for any reasons) or other agents for treating hot flashes (except stable dose of vitamin E is allowed as long as it was started > 30 days prior to study registration and are to be continued through the study period; soy is allowed, if it is planned to be continued at the same dose during the study period)
No current use of magnesium for any indication (except one standard multiple vitamin dose is allowed per day)
Not taking diuretics, corticosteroids, bile acid sequestrants, and other prescription and over-the-counter medications that may affect magnesium levels
No current ( 7 days prior to registration) or planned use of other non-drug therapies for managing hot flashes, such as acupuncture or yoga (use of these therapies for other reasons is allowed)
Inclusion Criteria:
female patients, >=18 years of age, with locally advanced breast cancer.
Exclusion Criteria:
previous therapy for any invasive malignancy. | Contradiction |
either surgical procedures or oral medication treatments are necessary components for participation in the primary clinical trial | INTERVENTION 1:
No Exercise
Multivitamin Arm + Calcitriol Arm:Calcitriol pill taken once per week
INTERVENTION 2:
Exercise
Exercise Arm: Exercise consisting of progressive walking and resistance band training
Calcitriol+ Exercise Arm: Calcitriol pill taken once per week + Exercise | Contradiction |
the primary trial involves administering medication through nasal and rectal routes, whereas the secondary trial delivers treatment via transdermal patches. | INTERVENTION 1:
Positron Emission Mammography
Positron Emission Mammography: Patients will receive bilateral (both sides) breast and axillary PEM scans, bilateral mammography, DCE-MRI, US of the breast and axilla (the side of the affected breast), and ultrasound guided biopsy of axillary lymph node if suspicious. Various PEM views will be performed on both your breast and axilla (underarm).
INTERVENTION 1:
Exemestane
Patients receive oral exemestane (25 mg) once daily for 5 years.
exemestane: Given orally
INTERVENTION 2:
Anastrozole
Patients receive oral anastrozole (1 mg) once daily for 5 years.
anastrozole: Given orally | Contradiction |
only female patients diagnosed with advanced colon cancer are considered eligible candidates for the primary clinical trial and the secondary clinical trial | Inclusion Criteria:
Females with histologic or cytologic diagnosis of advanced breast cancer. Lesions should not be amenable to surgery or radiation of curative intent.
Performance status of 0 to 2 on the Eastern Cooperative Oncology Group (ECOG) performance status scale.
One prior chemotherapy containing anthracyclines as (neo)adjuvant or palliative 1st-line treatment.
One prior chemotherapy containing taxanes as (neo) adjuvant or palliative 1st-line treatment.
Prior radiation therapy is allowed to less than 25% of the bone marrow. Participants must have recovered from the toxic effects of the treatment prior to study enrollment (except for alopecia). Prior radiotherapy must be completed 30 days before study entry. Lesions that have been radiated cannot be included as sites of measurable disease unless clear tumor progression has been documented in these lesions since the end of radiation therapy.
At least one uni-dimensionally measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Positron emission tomography [PET] scans and ultrasounds may not be used.
Antitumoral hormonal treatment must be discontinued prior to enrollment.
Estimated life expectancy of at least 3 months.
Participant compliance and geographic proximity that allow adequate follow-up.
Adequate organ function
Female participants of childbearing potential must test negative for pregnancy within 7 days of enrollment based on a urine and/or serum pregnancy test and agree to use a reliable method of birth control during and for 6 months following the last dose of study drug.
Participants must sign an informed consent document.
Female participants must be at least 18 years of age.
Exclusion Criteria:
Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
Have previously completed or withdrawn from this study or any other study investigating Pemetrexed, Gemcitabine, Carboplatin or Vinorelbine
Have received more than one line of chemotherapy in Metastatic Breast Cancer. Participants having received more than one combination of anthracycline plus taxane.
Are pregnant or breast-feeding.
Have serious concomitant systemic disorders (e.g., active infection) that, in the opinion of the investigator, would compromise the safety of the participant or compromise the participant's ability to complete the study.
Have a prior malignancy other than breast cancer, carcinoma in situ of the cervix, or nonmelanoma skin cancer, unless that prior malignancy was diagnosed and definitively treated at least 5 years previously with no subsequent evidence of recurrence.
Are unable to interrupt aspirin or other nonsteroidal anti-inflammatory agents for a 5-day period (8-day period for long-acting agents such as piroxicam), unless the Creatinine Clearance is greater than or equal to 80 ml/min.
Have central nervous system (CNS) metastases.
Have clinically relevant (by physical exam) third-space fluid collections (for example, ascites or pleural effusions) that cannot be controlled by drainage or other procedures prior to study entry.
Are unable or unwilling to take folic acid, vitamin B12 supplementation, or dexamethasone.
Concurrent administration of any other antitumor therapy.
Inclusion Criteria:
Confirmed hormone receptor positive advanced breast cancer, postmenopausal women
Exclusion Criteria:
Previous treatment for advanced breast cancer (previous treatment for early breast cancer is allowed). | Contradiction |
the least progression free survival(pfs) observed in cohort 1 of the primary clinical trial was lesser than 3 weeks | Outcome Measurement:
Progression Free Survival
PFS is defined as the period from the day of randomization until the first observation of lesion progression or death from any cause. Disease progression is defined as PD according to RECIST Ver. 1.1.
Assessment period was from the day of randomisation until the first observation of lesion progression or death
Time frame: Baseline, every 6 weeks of study treatment period, and end of study,
Results 1:
Arm/Group Title: NK105
Arm/Group Description: received NK105 (65 mg/m^2) on days 1, 8 and 15 of a 28-day cycle
Overall Number of Participants Analyzed: 211
Median (95% Confidence Interval)
Unit of Measure: months 8.4 (7.0 to 9.9)
Results 2:
Arm/Group Title: Paclitaxel
Arm/Group Description: received Paclitaxel (80 mg/m^2) on days 1, 8 and 15 of a 28-day cycle
Overall Number of Participants Analyzed: 211
Median (95% Confidence Interval)
Unit of Measure: months 8.5 (6.9 to 11.5) | Contradiction |
the primary trial reports the percentage of patients treated with Neratinib in Combination With Paclitaxel that suffer side effects that are serious enough to prevent an increase in dose or level of that treatment. cerebral blood flow assessment is an evaluation of the perfusion of blood through the brain. | Outcome Measurement:
Dose Limiting Toxicity Incidence of Neratinib in Combination With Paclitaxel
Dose Limiting Toxicity in subjects with solid tumors treated with neratinib, administered daily, in combination with paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28 day cycle.
Time frame: From first dose date through day 28
Results 1:
Arm/Group Title: Neratinib 160 mg + Paclitaxel 80 mg/m
Arm/Group Description: Neratinib 160 mg qd + Paclitaxel 80 mg/m IV on days 1, 8, and 15 of a 28 day cycle.
Overall Number of Participants Analyzed: 3
Measure Type: Count of Participants
Unit of Measure: Participants 0 0.0%
Results 2:
Arm/Group Title: Neratinib 240 mg + Paclitaxel 80 mg/m
Arm/Group Description: Neratinib 240 mg qd + Paclitaxel 80 mg/m IV on days 1, 8, and 15 of a 28 day cycle.
Overall Number of Participants Analyzed: 5
Measure Type: Count of Participants
Unit of Measure: Participants 0 0.0% | Entailment |
a patient group involved in the primary clinical trial underwent a placebo treatment | INTERVENTION 1:
Lapatinib 1500 mg
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.
INTERVENTION 2:
Placebo
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. | Entailment |
glucose urine excretion rate is a determination of the amount of glucose being excreted in urine over a defined period of time. eliane is a 56 year old woman, and alex is a 32 year old man, both eliane and alex can both be eligible for the primary trial. | Inclusion Criteria:
women >=18 years of age;
newly diagnosed;
infiltrating (invasive) HER2-neu-negative or HER2-neu-positive breast cancer.
Exclusion Criteria:
evidence of metastatic disease, except ipsilateral (same side) axillary lymph nodes;
previous systemic or local primary treatment. | Contradiction |
ability to participate in sexual activities is a question about an individual's ability to participate in sexual activities. The only case of congestive heart failure in the primary trial occurred in cohort 1. | Adverse Events 1:
Total: 1/35 (2.86%)
congestive heart failure *1/35 (2.86%)
Adverse Events 2:
Total: 0/40 (0.00%)
congestive heart failure *0/40 (0.00%) | Entailment |
candidates under the age of 18 are eligible for the primary clinical trial, even if their karnofsky score is below 80. | Inclusion Criteria:
Written informed consent
Operable breast cancer patients (T1-T3) with negative axillary lymph nodes (10 axillary nodes dissection) and high risk criteria according to St. Gallen consensus criteria.
Histologically proven breast cancer. Interval between surgery and registration is less than 60 days.
Definitive surgical treatment must be either mastectomy, or breast conservative surgery. Margins of resected specimen from surgery must be histologically free of invasive adenocarcinoma and ductal carcinoma in-situ (DCIS). Lobular carcinoma in-situ is not considered as positive margin.
Patients without proven metastatic disease.
Estrogen and progesterone receptors performed on the primary tumour prior to randomization.
Age between 18 years and 70 years.
Karnofsky performance status index > 80 %.
Adequate hepatic, renal and heart functions.
Adequate hematology levels.
Negative pregnancy test
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.
Bilateral invasive breast cancer.
Pregnant, or lactating patients.
Patients of childbearing potential must implement adequate non-hormonal contraceptive measures during study treatment .
Any T4 or N1-3 or M1 breast cancer.
Pre-existing motor or sensory neurotoxicity of a severity grade 2 by NCI criteria.
Other serious illness or medical condition
Past or current history of neoplasm other than breast carcinoma.
Ipsilateral ductal carcinoma in-situ (DCIS) of the breast.
Lobular carcinoma in-situ (LCIS) of the breast.
Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose
Concurrent treatment with ovarian hormonal replacement therapy. Prior treatment should be stopped before study entry.
Definite contraindications for the use of corticosteroids.
Concurrent treatment with other experimental drugs.
Participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry.
Concurrent treatment with any other anti-cancer therapy.
Male patients. | Contradiction |
the conclusions drawn from the primary clinical trial and secondary clinical trial are not equivalent or comparable. | Outcome Measurement:
Number of Participants With Complete Pathologic Response.
Pathologic complete response (pCR): Absence of invasive breast cancer in the breast (mastectomy or lumpectomy) specimen at the time of definitive surgery. Presence of in situ cancer alone will be considered a pCR.
Although clinical examination is the primary method of determining response, radiologic assessments (mammogram, ultrasound ± MRI) may be used to confirm response/non-response.
Time frame: assess at 8 weeks
Results 1:
Arm/Group Title: Trastuzumab and Abraxane Followed Trastuzumab and Vinorelbine
Arm/Group Description: Patients will be treated sequentially with preoperative trastuzumab and dose-dense ABI-007 followed by trastuzumab in combination with vinorelbine. Trastuzumab will be administered as a one-time loading dose of 4 mg/kg as a 90 minute infusion, followed by 20 weekly treatments at 2 mg/kg as a 30 minute infusion. ABI-007 will be administered every 2 weeks at a dose of 260mg/m2 as 30 minute infusion on the same days as trastuzumab for a total of 4 cycles (weeks 1 -8). Growth factor support with pegfilgrastim (Neulasta ) is required 24 to 48 hours following completion of each cycle of ABI-007. Beginning week 9, patients will then receive weekly vinorelbine at a dose of 25mg/m2 for 12 weeks on the same day as trastuzumab for a total of 4 cycles (weeks 9-20). As per standard treatment of HER2-positive breast cancers, patients will continue to receive trastuzumab every 3 weeks at 6 mg/kg beginning week 21 through week 52.
Overall Number of Participants Analyzed: 27
Measure Type: Number
Unit of Measure: participants 13
Outcome Measurement:
Change in Masood Score
Change in the semi-quantitative score assigned by the designated cytopathologist.
Range 6-24. Score represents increasing abnormality (i.e., worse appearance) Sum composite of 6 cytomorphological features, each scored as 1-4.
Time frame: Baseline to 6 months
Results 1:
Arm/Group Title: Placebo
Arm/Group Description: Placebo
Placebo: matched tablet dialy
Overall Number of Participants Analyzed: 84
Mean (Standard Deviation)
Unit of Measure: units on a scale -1.1 (1.9)
Results 2:
Arm/Group Title: Arzoxifene
Arm/Group Description: LY353381, 20 mg daily
arzoxifene: one tablet daily
Overall Number of Participants Analyzed: 82
Mean (Standard Deviation)
Unit of Measure: units on a scale -0.8 (2.1) | Entailment |
the primary clinical trial and the secondary clinical trial do not admit women currently under endocrine therapy | Inclusion Criteria:
No known soy intolerance
At increased risk of developing breast cancer in >= 1 previously unaffected breast, as defined by any of the following:
Estimated 5-year risk of developing breast cancer using the Gail model, as defined by 1 of the following:
Gail score >= 1.66%
Gail score >= 0.1% for women age 20-29 years
Gail score >= 1.0% for women age 30-39 years
Estimated 5-year risk of developing breast cancer using the Claus model:
Claus score >= 1.66%
Claus score >= 0.1% for women age 20-29 years
Claus score >= 1.0% for women age 30-39 years
Prior diagnosis of unilateral in situ or invasive breast cancer OR history of atypical hyperplasia, BRCA 1 and/or BRCA 2 positivity
History of lobular carcinoma in situ
No evidence of breast cancer, as determined by a negative mammogram within the past 6 months and a history and physical
No previously diagnosed breast cancer unless all systemic therapy (including endocrine therapy) was completed at least 1 year ago
Pre- or postmenopausal
ECOG performance status 0-1
Hemoglobin > 10.0 g/dL
Platelet count > 100,000/mm^3
Absolute neutrophil count > 1,000/mm^3
Creatinine < 2.0 mg/dL
SGPT < 82 U/L
SGOT < 68 U/L
Bilirubin < 3 mg/dL* [Note: * Patients with a higher level of bilirubin due to a familial metabolism may be eligible at the discretion of the investigator]
Life expectancy > 2 years
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception
Must be willing to keep a dietary diary
No venous thrombosis within the past year
No unrecognized or poorly controlled thyroid disease
No other cancer within the past 5 years except nonmelanomatous skin cancer or noninvasive cervical cancer
No other medical condition that, in the opinion of the investigator, would jeopardize either the patient or the integrity of the data obtained
None of the following for >= 2 weeks before the first random fine needle aspiration and during study participation:
Oral contraceptives
Soy supplements
High soy-containing foods
Fish oil supplements
Multivitamins
Vitamins C and E
Daily aspirin or nonsteroidal
Anti-inflammatory drugs
No other concurrent investigational agents
No concurrent warfarin or other blood thinners
Female patient
Exclusion Criteria:
Women previously diagnosed with breast cancer will not be eligible unless all systemic therapy (including endocrine therapy) was completed at least one year previously
Currently pregnant, or planning to become pregnant during the study period
History of venous thrombosis within past year
Medical conditions, which, in the opinion of the investigators would jeopardize either the patient or the integrity of the data obtained
History of other cancer within the past five years, excluding non-melanomatous skin cancer, and non-invasive cervical cancer
Known soy intolerance
Unrecognized or uncontrolled thyroid disease, subjects may be on synthroid, but thyroid function must be in normal range or the patient's physician must document that the patient's thyroid is controlled.
Currently receiving any other investigational agents
Currently on coumadin, or other blood thinners
History of breast augmentation implants.
Rusults from patients who have <4000 epithelial cells in either the first or the second random Fine-needle aspiration (rFNA) will not be included in the study.
Inclusion Criteria:
Female aged 18 years.
Patients with pathologically documented metastatic triple negative breast cancer (TNBC), eligible for treatment with paclitaxel. Paraffin-embedded tissue must be available from metastatic sites, if reasonably accessible, or from the primary tumor, to confirm the diagnosis of TNBC and for correlative studies (only on metastatic tissue). Fifteen slides can be obtained if the full block is not available to be sent or released.
TNBC will be defined as breast cancer with <1% ER+ and <1% PgR+ cells, and HER2 immunohistochemistry score of 0 or 1+ and/or in situ hybridization (ISH) with HER2 gene copy number <4 or a ratio of less than 2 between HER2 gene copy number and centromere of chromosome 17. Patients whose metastatic disease is TNBC are eligible even when their primary tumor expressed hormone receptors and/or HER2.
Patients must be newly diagnosed metastatic or must have relapsed following a prior (neo)adjuvant chemotherapy regimen. If a taxane (i.e., paclitaxel or docetaxel) was administered as part of the (neo)adjuvant regimen, PD must have occurred > 12 months from the end of previous (neo)adjuvant treatment. For non-taxane (neo)adjuvant regimen, PD must have occurred > 6 months from the end of previous (neo)adjuvant treatment
Patients with at least one baseline measurable lesion according to RECIST criteria version 1.1.
Zubrod (Eastern Co-operative Oncology Group [ECOG]) Performance Status (PS) of 0-1.
Life expectancy of at least three months.
Patients must be able to swallow and retain oral medication (intact tablet).
Able to undergo all screening assessments outlined in the protocol.
Adequate organ function (defined by the following parameters):
Serum creatinine < 140 μmol/L (< 1.6 mg/dL) or creatinine clearance > 60 mL/min.
Serum hemoglobin 9 g/dL; absolute neutrophil count 1.5 x 109/L; platelets 100 x 109/L.
Serum bilirubin 1.5 x upper normal limit (UNL) except patients with Gilbert's syndrome
Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) 2.5 x UNL but 5.0 x UNL in case of liver metastases; alkaline phosphatase (ALP) UNL but i) 2.5 x UNL in case of liver metastases and ii) 5 UNL in case of bone metastases; albumin 2.5 g/dl.
No history or evidence by CT scan or MRI, of brain metastases or leptomeningeal disease.
No known hepatitis B virus (not due to immunization), hepatitis C virus, human immunodeficiency virus-I and -II positive status.
Dated and signed IEC/IRB-approved informed consent.
Exclusion Criteria:
Prior therapy for metastatic TNBC (chemotherapy, hormone therapy or biological therapy), Patients may receive bisphosphonates and other therapies to treat bone metastases, however if used, bone lesions will not be considered as measurable disease.
Less than four weeks since last radiotherapy (excluding palliative radiotherapy).
Pregnancy or lactation or unwillingness to use adequate method of birth control.
Neurological or psychiatric disorders which may influence understanding of study and informed consent procedures.
Active or uncontrolled infection.
Malabsorption syndrome, disease significantly affecting gastrointestinal function.
G>1 pre-existing peripheral neuropathy
Any other invasive malignancy from which the patient has been disease-free for less than 5 years with the exception of curatively treated basal or squamous cell skin cancer
Hypersensitivity to:
paclitaxel
ibuprofen or to more than one non-steroidal anti-inflammatory drug.
medications belonging to the class of sulfonamides, with the exception of sulfanilamides (e.g., sulfamethoxazole). | Entailment |
grade 3b follicular lymphoma is a grade 3 follicular lymphoma composed of solid sheets of centroblasts. Patients must be able to undergo a PET scan to participate in the primary trial. | Inclusion Criteria:
Pathologically confirmed breast cancer, determined to be a candidate for primary systemic (neoadjuvant) therapy and for surgical resection of residual primary tumor following completion of neoadjuvant therapy
Locally advanced breast cancer, not stage IV, and with a tumor size >= 2 cm (as measured on imaging or estimated by physical exam)
No obvious contraindications for primary chemotherapy
Residual tumor planned to be removed surgically following completion of neoadjuvant therapy
Able to lie still for 1.5 hours for PET scanning
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
Leukocytes >= 3,000/ul
Absolute neutrophil count >= 1,500/ul
Platelets >= 100,000/ul
Total bilirubin within normal institutional limits
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 times the institutional upper limit of normal
Creatinine within normal institutional limits OR creatinine clearance >= 30 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
If female, postmenopausal for a minimum of one year, OR surgically sterile, OR not pregnant, confirmed by institutional standard of care (SOC) pregnancy test, and willing to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation
Able to understand and willing to sign a written informed consent document and a Health Insurance Portability and Accountability Act (HIPAA) authorization in accordance with institutional guidelines
Exclusion Criteria:
Previous treatment (chemotherapy, radiation, or surgery) to involved breast; including hormone therapy
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
Medically unstable
Condition requiring anesthesia for PET scanning and/or unable to lie still for 1.5 hours
History of allergic reactions attributed to compounds of similar chemical or biologic composition to F-18 fluorothymidine
Pregnant or nursing
Previous malignancy, other than basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, from which the patient has been disease free for less than 5 years
Currently on hormone therapy as the primary systemic neoadjuvant therapy | Entailment |