Ipatasertib in Combination With Carboplatin, Carboplatin/Paclitaxel, or Capecitabine/Atezolizumab in Treating Patients With Metastatic Triple Negative Breast Cancer

Summary

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Description

PRIMARY OBJECTIVES: I. To determine the recommended phase II dose (RP2D) of ipatasertib plus carboplatin/paclitaxel (arm A), ipatasertib plus carboplatin (arm B), and ipatasertib, atezolizumab, and capecitabine (arm C) in patients with metastatic triple negative breast cancer (TNBC). (Phase I) II. T...

PRIMARY OBJECTIVES: I. To determine the recommended phase II dose (RP2D) of ipatasertib plus carboplatin/paclitaxel (arm A), ipatasertib plus carboplatin (arm B), and ipatasertib, atezolizumab, and capecitabine (arm C) in patients with metastatic triple negative breast cancer (TNBC). (Phase I) II. To obtain initial evidence of activity by examining progression free survival for each dose regimen. (Phase IB) SECONDARY OBJECTIVES: I. To confirm the recommended phase II dose (RPIID) safety in expanded cohort by evaluating toxicities and confirm tolerability of the combinations. II. To obtain evidence of activity by examining response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. III. To evaluate clinical benefit rate (CBR), event-free survival, time-to-treatment failure and overall survival. IV. Further describe the cumulative toxicities (Common Terminology Criteria for Adverse Events [CTCAE] 5.0) of the combinations. V. To evaluate patient's quality of life (QOL). EXPLORATORY OBJECTIVES: I. To evaluate the progression-free survival and overall survival, based on the genomic alterations including PIK3CA/AKT/PTEN alterations and BRCA status. II. To study the association of TNBC messenger ribonucleic acid (mRNA) expression profiling including Vanderbilt molecular subtype and treatment response. III. To study the association of stool microbiome, calprotectin with diarrhea. IV. To study peripheral blood circulating tumor deoxyribonucleic acid (DNA). V. To study therapy resistance by analyzing tumor genomics and transcriptome analysis. VI. To study the profiles of peripheral blood mononuclear cells and its association with response to therapy. VII. To study genomic immune biomarkers and its association with response. OUTLINE: This is a phase I, dose-escalation trial of ipatasertib, followed by a phase II trial. Patients are randomized or assigned to 1 of 3 arms depending on available slots. ARM A: Patients receive ipatasertib orally (PO) once daily (QD) on days 1-28. Patients also receive carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 60 minutes on days 1, 8, and 15 or days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive ipatasertib PO QD on days 1-28. Patients also receive carboplatin IV over 30 minutes on days 1, 8, and 15 or days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM C: Patients receive ipatasertib PO QD on days 1-21, capecitabine PO twice daily (BID) on days 1-7 and 15-21, and atezolizumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 36 months.

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