Clinical Trials Logo

Clinical Trial Summary

This randomized phase II trial studies how well cisplatin works with or without veliparib in treating patients with triple-negative breast cancer and/or BRCA mutation-associated breast cancer that has come back (recurrent) or has or has not spread to the brain (brain metastases). Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as veliparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. It is not yet known if cisplatin is more effective with or without veliparib in treating patients with triple-negative and/or BRCA mutation-associated breast cancer.


Clinical Trial Description

PRIMARY OBJECTIVES: I. To compare the efficacy of cisplatin with or without ABT-888 (veliparib) on progression-free survival (PFS) in each of the following groups: Ia. Patients with germline BRCA (gBRCA) mutation-associated breast cancer. Ib. Patients with germline BRCA wild-type breast cancer who have evidence of BRCAness phenotype. Ic. Patients with germline BRCA wild-type breast cancer who do not have evidence of BRCAness phenotype. II. To compare the efficacy of cisplatin with or without ABT-888 on PFS in patients with triple negative and/or gBRCA mutation-associated breast cancer and brain metastases. (Brain Metastases Cohort) SECONDARY OBJECTIVES: I. For patients with gBRCA mutation associated breast cancer (group "i" above) or triple-negative breast cancer (TNBC) with (group "ii") or without (group "iii") BRCAness phenotype, to compare the efficacy of cisplatin with or without ABT-888 on overall survival (OS), response rate, and clinical benefit rate. II. To compare the differential benefit of ABT-888 across the three groups using both PFS and OS as outcomes. III. For patients in the brain metastases cohort, to compare the efficacy of cisplatin with or without ABT-888 on OS. IV. For patients in the brain metastases cohort, to compare the efficacy of cisplatin with or without ABT-888 on intracranial and extracranial response rates (intracranial by Response Assessment Neuro-Oncology Criteria [RANO] and extracranial by Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST 1.1]). V. To compare toxicities of ABT-888 to placebo in each of the four groups separately. TRANSLATIONAL OBJECTIVES: I. To evaluate the impact of homologous recombination deficiency score (independent of other BRCAness markers) on response rate (RR) and PFS in patients treated with chemotherapy versus chemotherapy plus ABT-888. II. To evaluate the overlap among various markers utilized to define the BRCAness phenotype. III. To evaluate the combined impact of PAM50 basal subtype and BRCAness phenotype on RR and PFS in patients treated with chemotherapy versus chemotherapy plus ABT-888. IV. To evaluate the impact of BRCA1 mRNA expression (independent other BRCAness markers) on response rate (RR) and PFS in patients treated with chemotherapy versus chemotherapy plus ABT-888. V. Application of somatic BRCAness phenotype markers on metastatic tumor tissue to identify patients likely to benefit from platinum-based therapy and ABT-888. VI. To determine the overlap of BRCA phenotype (germline BRCA, BRCA-like, non-BRCA-like) with tissue PD-L1 status and to determine if ABT-888 (veliparib) benefit in BRCA-like patients is maintained when adjusting for PD-L1 status. VII. To evaluate circulating tumor cells - homologous recombination deficiency (CTC-HRD) status as a predictive biomarker of response to treatment with cisplatin plus ABT-888 (veliparib) versus cisplatin plus placebo. VIII. To evaluate circulating tumor deoxyribonucleic acid (ctDNA) HRR (homologous recombination repair) mutation status as a predictive marker of response to treatment with cisplatin plus ABT-888 (veliparib) versus cisplatin plus placebo. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cisplatin intravenously (IV) over 1 hour on day 1 and placebo orally (PO) twice daily (BID) on days 1-14. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive cisplatin IV over 1 hour on day 1 and veliparib PO BID on days 1-14. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 9 weeks for 54 weeks, every 18 weeks until progression, and then every 6 months for up to 5 years after registration. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02595905
Study type Interventional
Source National Cancer Institute (NCI)
Contact
Status Active, not recruiting
Phase Phase 2
Start date September 15, 2016
Completion date October 31, 2024

See also
  Status Clinical Trial Phase
Active, not recruiting NCT04052555 - Testing the Addition of an Anti-cancer Drug, Berzosertib, to the Usual Treatment (Radiation Therapy) for Chemotherapy-Resistant Triple-Negative and Estrogen and/or Progesterone Receptor Positive, HER2 Negative Breast Cancer Phase 1
Recruiting NCT04521764 - A Vaccine (MV-s-NAP) for the Treatment of Patients With Invasive Metastatic Breast Cancer Phase 1
Completed NCT00100750 - Tipifarnib and Gemcitabine Hydrochloride in Treating Women With Metastatic Breast Cancer Phase 1/Phase 2
Suspended NCT03737695 - Clinical Information and Biospecimen Collection From Patients With Recurrent or Stage IV Breast Cancer
Terminated NCT02149173 - F-18 FES PET/CT in Measuring Hormone Expression in Patients With Primary, Recurrent, or Metastatic Breast Cancer Undergoing Endocrine-Targeted Therapy N/A
Completed NCT00390455 - Fulvestrant With or Without Lapatinib in Treating Postmenopausal Women With Stage III or Stage IV Breast Cancer That is Hormone Receptor-Positive Phase 3
Recruiting NCT03213041 - Pembrolizumab and Carboplatin in Treating Patients With Circulating Tumor Cells Positive Metastatic Breast Cancer Phase 2
Not yet recruiting NCT04529044 - 177Lu-DOTATATE for the Treatment of Stage IV or Recurrent Breast Cancer Phase 2
Completed NCT00699491 - Cixutumumab and Temsirolimus in Treating Patients With Locally Recurrent or Metastatic Breast Cancer Phase 1/Phase 2
Completed NCT03364348 - 4-1BB Agonist Monoclonal Antibody PF-05082566 With Trastuzumab Emtansine or Trastuzumab in Treating Patients With Advanced HER2-Positive Breast Cancer Phase 1
Terminated NCT01149356 - RO4929097 And Exemestane in Treating Pre- and Postmenopausal Patients With Advanced or Metastatic Breast Cancer Phase 1
Completed NCT01964924 - Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Metastatic Triple-Negative Breast Cancer Phase 2
Completed NCT00785291 - Paclitaxel, Nab-paclitaxel, or Ixabepilone With or Without Bevacizumab in Treating Patients With Stage IIIC or Stage IV Breast Cancer Phase 3
Terminated NCT02370264 - Questionnaires in Identifying Upper Extremity Function and Quality of Life After Treatment in Patients With Breast Cancer N/A
Terminated NCT01071564 - RO4929097 and Vismodegib in Treating Patients With Breast Cancer That is Metastatic or Cannot Be Removed By Surgery Phase 1
Terminated NCT00998738 - Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer Phase 3
Active, not recruiting NCT00520975 - First-Line Chemotherapy and Trastuzumab With or Without Bevacizumab in Treating Patients With Metastatic Breast Cancer That Overexpresses HER-2/NEU Phase 3
Completed NCT01251874 - Veliparib and Carboplatin in Treating Patients With HER2-Negative Metastatic Breast Cancer Phase 1
Active, not recruiting NCT03281902 - Genetic Analysis in Blood and Tumor Samples From Patients With Advanced or Metastatic Estrogen Receptor Positive and HER2 Negative Breast Cancer Receiving Palbociclib and Endocrine Therapy
Recruiting NCT03987555 - Paclitaxel Therapeutic Drug Monitoring in Cancer Patients