Phase 1 Trial of ABT-888 and SCH727965 Without or With Carboplatin in Patients With Advanced Solid Tumors
I. To evaluate the safety and tolerability of veliparib (ABT-888) and dinaciclib (SCH727965)
without or with carboplatin in patients with advanced solid tumors.
II. To determine the recommended phase 2 dose (RP2D) for ABT-888 in combination with
SCH727965 without or with carboplatin, determined by evaluating the feasibility, safety,
dose-limiting toxicities, and the maximally tolerated dose(s).
I. To confirm the safety of the combination of ABT-888 and SCH727965 without or with
carboplatin 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 without or with carboplatin.
III. To assess the pharmacodynamic effects of ABT-888 in combination with SCH727965 without
or with carboplatin, both in surrogate tissues and in tumor.
IV. To assess preliminary antitumor activity of the ABT-888/SCH727965 and
ABT-888/SCH727965/carboplatin combinations in subjects with solid tumors.
OUTLINE: This is a dose-escalation study of veliparib and dinaciclib followed by an expanded
BRCA-proficient and BRCA-deficient cohort study.
PART 1: Patients receive veliparib orally (PO) twice daily (BID) on days 1-28 and dinaciclib
IV over 2 hours on days 8 and 22. Courses repeat every 28 days in the absence of disease
progression or unacceptable toxicity. Once the maximum-tolerated dose (MTD) is determined,
part 2 of study is initiated.
PART 2: Patients receive veliparib and dinaciclib as patients in part 1. Patients also
receive carboplatin IV over 60 minutes on days 8 and 22. Courses repeat every 28 days in the
absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection at baseline and periodically during study for
pharmacokinetic and pharmacodynamic studies, circulating tumor cells, and other correlative
studies. Patients also undergo skin biopsy at baseline and on day 8 for correlative studies.
Some patients undergo tumor biopsy (Tru-cut or core biopsy) on days 6 or 7 and 9 or 10 for
correlative studies. Archived tumor tissue from diagnosis may also be obtained.
After completion of study treatment, patients are followed up every 3 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase 2 dose of veliparib/dinaciclib with or without carboplatin determined by dose-limiting toxicities graded according to the NCI Common Terminology Criteria for Adverse Events (version 4.0)
Frequency tables of worst grade of adverse event, drug-related adverse events, and worst grade of laboratory value will be presented by dose cohort.
Dana-Farber Cancer Institute
United States: Food and Drug Administration
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|