Testing the Addition of the Anti-Cancer Drug Talazoparib to the Combination of Carboplatin and Paclitaxel for the Treatment of Advanced Cancer

Summary

Participation Requirements

Description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of talazoparib (BMN 673) seven day schedule in combination with carboplatin and paclitaxel. II. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of talazoparib (B...

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of talazoparib (BMN 673) seven day schedule in combination with carboplatin and paclitaxel. II. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of talazoparib (BMN 673) three day schedule in combination with carboplatin and paclitaxel. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity of talazoparib (BMN 673) in combination with carboplatin and paclitaxel. II. To determine whether the pharmacokinetic parameters of talazoparib (BMN 673) when given in combination with carboplatin and paclitaxel correlate with thrombocytopenia. III. To observe and record anti-tumor activity of talazoparib (BMN 673) alone after the combination with carboplatin, paclitaxel and talazoparib (BMN 673). IV. To observe the safety and tolerability of talazoparib (BMN 673) in combination with paclitaxel and carboplatin and talazoparib (BMN 673) alone after the combination therapy. EXPLORATORY OBJECTIVES: I. To serially evaluate pharmacokinetic and pharmacodynamics parameters and use indirect pharmacokinetic/pharmacodynamics models to correlate with tumor response and resistance to the combination talazoparib (BMN 673), carboplatin, and paclitaxel therapy. II. To explore mechanisms of resistance to the combination of talazoparib (BMN 673) with carboplatin and paclitaxel. OUTLINE: This is a dose-escalation study of talazoparib. Patients are assigned to 1 of 2 dosing schedules. SCHEDULE A: Patients receive talazoparib orally (PO) once daily (QD) on days 1-7, paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. SCHEDULE B: Patients receive talazoparib PO QD on days 1-3, paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. At any time after 4-6 cycles of treatment, patients may continue combination study therapy with talazoparib, carboplatin, and paclitaxel, talazoparib and carboplatin, talazoparib alone (continuous dosing), or observation without therapy at the discretion of the treating physician. After completion of study treatment, patients are followed up for 4 weeks.

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