Veliparib and Dinaciclib in Treating Patients With Advanced Solid Tumors

Description

PRIMARY OBJECTIVES:

I. To evaluate the safety and tolerability of veliparib (ABT-888) and dinaciclib (SCH727965) in patients with advanced solid tumors.

II. To determine the recommended phase 2 dose (RP2D) for ABT-888 in combination with SCH727965, determined by evaluating the feasibility, safety, dose-limiting toxicities, and the maximally tolerated dose(s).

SECONDARY OBJECTIVES:

I. To confirm the safety of the combination of ABT-888 and SCH727965 in patients with known BRCA1 or BRCA2 germline mutation.

II. To characterize the pharmacokinetic parameters of ABT-888 both alone and in combination with SCH727965.

III. To assess the pharmacodynamic effects of ABT-888 in combination with SCH727965, both in surrogate tissues and in tumor.

IV. To assess preliminary antitumor activity of the ABT-888/SCH727965 combinations in subjects with solid tumors.

OUTLINE: This is a dose-escalation study of veliparib and dinaciclib followed by expanded doublet cohort studies of non-breast BRCA-proficient patients and BRCA-proficient triple negative breast cancer (TNBC) patients, a safety doublet cohort for BRCA-deficient patients, and cohorts of BRCA-associated TNBC (PARP inhibitor-naive and PARP inhibitor-resistant).

PART 1A: Patients receive veliparib orally (PO) twice daily (BID) on days 1-28 and dinaciclib intravenously (IV) over 2 hours on days 8 and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PART 1B: Patients receive veliparib and dinaciclib as patients in Part 1A. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

PART 1C: Patients receive veliparib PO BID on days 1-7 of cycle 0. Patients then receive veliparib PO BID on days 1-21 and dinaciclib IV over 2 hours on days 1, 4, 8, and 11 or days 1 and 8. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

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