Cisplatin vs Paclitaxel for Triple Neg BRCA

Status: Recruiting
Phase: Phase 2
Diagnosis: Breast: Metastatic, Breast: Early Stage Disease
NCT ID: NCT01982448 (View complete trial on ClinicalTrials.gov)
DFCI Protocol ID: 13-383

 

This research study is evaluating how well triple negative breast cancer responds to preoperative treatment with Cisplatin or Paclitaxel chemotherapy, and if use of a research test Homologous Recombination Deficiency (HRD) assay can predict response to preoperative treatment.

 

Conducting Institutions:
Brigham and Women's Hospital, Dana-Farber Cancer Institute, Beth-Israel Deaconess Medical Center

Overall PI:
Erica Mayer, MD, Dana-Farber Cancer Institute

Site-responsible Investigators:
Nadine Tung, MD, Beth Israel Deaconess Medical Center

Contacts:
Dana-Farber Cancer Institute: Breast Cancer Nursing Team, 617-632-3478
Beth-Israel Deaconess Medical Center: Cancer Trials Call Center, 617-667-3060

Eligibility Criteria

Inclusion Criteria: - Participants must meet the following criteria on screening examination to be eligible to participate in the study - Pathologic documentation of invasive breast cancer by biopsy (FNA alone is not adequate). - AJCC clinical stage I with T1 > 1.5 cm, stage II or III invasive breast cancer. - Participants with multicentric or bilateral disease are eligible if at least one lesion meets stage eligibility criteria for the study and no tumor is HER2-positive. In this circumstance, the investigator must determine which will represent the target lesion to be assessed for response. This should remain consistent throughout the study. The target lesion should be selected on the basis of its size (lesion with the longest diameter) and suitability for accurate repetitive measurements. - Tumors must be HER2 negative defined as HER2 0 or 1+ by immunohistochemistry (IHC) assays and /or lack of gene amplification by FISH defined as a ratio < 2 on invasive tumor by local review. - ER and PgR status by IHC must be known. Tumor must be ER and PR negative (<1% staining) by local review. - Participant should have negative germline testing for BRCA1/2 gene mutations. Subjects who are considered otherwise eligible for the trial will have BRCA1/2 testing performed on an expedited basis as part of screening. If a potential subject does not have insurance coverage for testing or if results from available testing options will not be ready in time for enrollment in the study, costs for this test will be covered by the study. This form may also be used for genetic testing which will be covered by the participant's insurance and may lead to more expedited testing. - Participants with a germline deleterious BRCA mutation or BRCA1 or BRCA2 classified as "variant, suspected deleterious" by Myriad Genetics will not be eligible for the trial. Participants without a mutation or with only a BRCA1 or BRCA2 VUS (variant of uncertain significance) as classified by Myriad Genetics will be eligible for this study. - Although strongly recommended, genetic testing will not be mandatory. If a patient refuses to perform genetic testing but is otherwise eligible for the study, enrollment will be allowed. - Breast imaging should include imaging of the ipsilateral axilla. For subjects with a clinically positive axilla, a needle aspiration, core biopsy or SLN procedure will be performed to confirm the presence of metastatic disease in the lymph nodes. For patients with a clinically negative axilla, baseline assessment of the axilla will be performed at the discretion of the treating investigator. For patients with pathologically positive axillary lymph nodes prior to preoperative therapy, a level I and II lymph node dissection at the time of definitive surgery is recommended. - Participants with axillary adenopathy only are not eligible for this study. - Patients with a prior history of contra-lateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer within the last 5 years. - Women ≥ 18 years of age. - ECOG performance status ≤1 (see Appendix A). Laboratory Evaluation - Absolute neutrophil count (ANC) ≥ 1,500 / mm3 - Platelet count ≥ 100,000/ mm3 - Bilirubin ≤ 1.5x upper limit of normal (ULN), for patients with Gilbert syndrome, direct bilirubin will be measured instead of total bilirubin ALT, AST, ALK Phos ≤2.5 x ULN - Creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 cc/min - Hemoglobin ≥ 9 mg/dl - Use of an effective means of contraception is required in subjects of childbearing potential since study agents are known to be teratogenic. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. - Ability to understand and the willingness to sign a written informed consent document - Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy and did not receive prior chemotherapy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. - Patient must be willing to undergo mandatory research biopsy and blood draw. Prior to biopsy procedures patients must be able to be off medications that could increase the risk of bleeding Exclusion Criteria: - Any prior chemotherapy at any time. - Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy. - Ipsilateral breast recurrence, unless prior treatment consisted of excision alone for DCIS or breast conserving treatment and hormonal therapy for DCIS or invasive breast cancer. - Ongoing use of any other investigational or study agents. - Peripheral neuropathy of any etiology > grade 1 (NCI CTCAE Version 4.0- Appendix B) - Significant hearing loss that would prevent cisplatin administration. - Renal dysfunction for which exposure to cisplatin would be unsafe or require cisplatin dose modification (i.e., Cre > 1.5 mg/dl or GFR < 60 cc/min).
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