Ignite Creation Date:
2025-12-25 @ 3:27 AM
Ignite Modification Date:
2026-01-13 @ 7:26 PM
Study NCT ID:
NCT02595905
Status:
COMPLETED
Last Update Posted:
2025-05-16
First Post:
2015-11-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Cisplatin With or Without Veliparib in Treating Patients With Recurrent or Metastatic Triple-Negative and/or BRCA Mutation-Associated Breast Cancer With or Without Brain Metastases
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
Phase II Randomized Placebo-Controlled Trial of Cisplatin With or Without ABT-888 (Veliparib) in Metastatic Triple-Negative Breast Cancer and/or BRCA Mutation-Associated Breast Cancer, With or Without Brain Metastases
Status:
COMPLETED
Status Verified Date:
2025-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
Detailed 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.
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 Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: