An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors
I. To determine the pharmacokinetics and pharmacodynamics of ABT-888 (veliparib) in patients
with varying degrees of renal or hepatic dysfunction.
II. To determine the maximum-tolerated dose (MTD) of ABT-888 in combination with carboplatin
and paclitaxel for patients with varying degrees of liver or kidney dysfunction.
III. To provide dosing recommendations for ABT-888 in combination with carboplatin and
paclitaxel based on degree of hepatic and renal impairment.
I. To define the dose-limiting toxicity (DLT) and other toxicities associated with the use
of this combination in patients with varying degrees of renal or hepatic dysfunction.
II. To evaluate the pharmacokinetic parameters of ABT-888, carboplatin, and paclitaxel when
administered as a combination in patients with varying degrees of renal of hepatic
III. To evaluate the pharmacodynamic measurement of poly-ADP-ribosylated (PAR) and platinum
adducts in tumor cells associated with the use of this combination in patients with varying
degrees of renal or hepatic dysfunction.
OUTLINE: This is a multicenter, dose-escalation study of veliparib. Patients are stratified
according to degree of renal dysfunction (normal vs moderate vs severe vs very severe) or
hepatic dysfunction (mild vs mild with transaminase elevation vs moderately severe vs
Patients receive veliparib* orally (PO) twice daily (BID) on days 1-7 and paclitaxel
intravenously (IV) over 3 hours and carboplatin IV over 30 minutes on day 3. Courses repeat
every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Blood and hair follicle samples are collected at baseline, on days -5 or -6, and on day 3 of
course 1 for pharmacokinetic and pharmacodynamic studies. Tumor tissue biopsies may also be
collected at baseline and on day 3.
After completion of study therapy, patients are followed up for 4 weeks.
NOTE: * All patients receive a single dose of veliparib PO on day -6 before course 1 (except
patients with very severe renal dysfunction who receive veliparib on day -5 or -6 to
coincide with a dialysis day).
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of veliparib in combination with carboplatin and paclitaxel using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0
Up to day 21
University of Pittsburgh
United States: Food and Drug Administration
|Albert Einstein College of Medicine||Bronx, New York 10461|
|Johns Hopkins University||Baltimore, Maryland 21205|
|Memorial Sloan Kettering Cancer Center||New York, New York 10021|
|University of Pittsburgh Cancer Institute||Pittsburgh, Pennsylvania 15213|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|University of Wisconsin Hospital and Clinics||Madison, Wisconsin 53792-0001|
|Montefiore Medical Center||Bronx, New York 10467-2490|
|City of Hope||Duarte, California 91010|
|Case Western Reserve University||Cleveland, Ohio 44106|
|Emory University||Atlanta, Georgia 30322|
|Wayne State University||Detroit, Michigan 48202|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|Penn State Milton S Hershey Medical Center||Hershey, Pennsylvania 17033|
|City of Hope- South Pasadena Cancer Center||South Pasadena, California 91030|
|Seidman Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center||Cleveland, Ohio 44106|