Study of BMN-673 With Carboplatin and Paclitaxel in Patients With Advanced BRCA-mutated Solid Tumor or Triple Negative Metastatic Breast Cancer
|Triple Negative Metastatic Breast Cancer BRCA-mutated Solid Tumor||Drug: BMN-673 Drug: Carboplatin Drug: Paclitaxel||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Phase I Study to Evaluate the Tolerability, Safety and Efficacy of BMN-673 in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumor Malignancies That Have BRCA Mutations or Triple Negative Metastatic Breast Cancer|
- Overall Response Rate (ORR) [ Time Frame: From date of randomization until the date of Initial response to the first documented tumor progression or date of death from any cause, up to 18 months. ]Response rate of combination (BMN 673 + carboplatin) in patients with BRCA germline mutations or triple negative cancer without known BRCA mutations, in solid tumor malignancies with paclitaxel with a 15 patient cohort expansion at the MTD. Response and progression in this study will be evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee.
- Intolerable Toxicity [ Time Frame: From first dose to 30 day follow up. ]Analyses of adverse events will be performed for all patients having received at least one dose of study drug. The study will use the CTCAE v4.0 for reporting of non-hematologic adverse events.
|Actual Study Start Date:||February 23, 2015|
|Estimated Study Completion Date:||June 2020|
|Primary Completion Date:||January 1, 2016 (Final data collection date for primary outcome measure)|
BMN-673: Oral, every day, Days 1-21; Carboplatin: intravenous, every week, 750 μg/day; Paclitaxel: intravenous, every week, 0.75 x Maximum Tolerated Dose μg/day
|Drug: BMN-673 Drug: Carboplatin Drug: Paclitaxel|
PARP1/2 inhibitors are a novel class of anticancer agents that have shown activity in tumors with defects in DNA repair and may induce synthetic lethality in combination with agents that induce DNA damage by preventing DNA repair.
The rationale of this study is to determine whether a DNA damaging agent can potentiate the cell death induced by PARP inhibitors in individuals with tumor that are more susceptible to chemotherapy.
The study will evaluate the potential benefits of BMN 673 in combination with weekly carboplatin in patients with metastatic tumors associated with BRCA germ line mutations or patients with triple negative breast cancer with no known BRCA mutation, subsequently if tolerated, an additional cohort will examine the feasibility of adding paclitaxel to this combination for any solid tumor malignancies with potential benefit to this combination.
This is the first study to evaluate the safety and efficacy of BMN 673 in combination with carboplatin in patients with either BRCA mutations or TNBC. If tolerable paclitaxel will be added to the combination in any solid tumor malignancies with potential benefit to this combination.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02358200
|United States, California|
|University of California San Francisco|
|San Francisco, California, United States, 94115|