Phase I Study of ABT-888 in Combination With Gemcitabine in Patients With Advanced Malignancies
I. Establish the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of the
combination of ABT-888 and gemcitabine (gemcitabine hydrochloride) in patients with advanced
I. Establish the safety and tolerability of the combination of ABT-888 and gemcitabine in
patients with solid tumors.
II. Determine the effects of ABT-888 and gemcitabine treatment on DNA damage response by
analysis of markers such as Ataxia telangiectasia mutated (ATM) in peripheral blood
mononuclear cells (PBMCs).
III. Determine the pharmacokinetics of ABT-888 and gemcitabine when administered in
IV. Determine the generation of gemcitabine triphosphate in PBMCs. V. Document any evidence
of antitumor response.
OUTLINE: This is a dose-escalation study.
Patients receive oral ABT-888 twice daily on days 1-14 and gemcitabine hydrochloride IV over
30 minutes on days 1, 8, and 15. Courses repeat every 21* days in the absence of disease
progression or unacceptable toxicity.
After completion of study therapy, patients are followed up for at least 4 weeks.
NOTE: *Patients previously enrolled on a 4-week schedule (ABT-888 twice daily on days 1-21
with gemcitabine IV over 30 minutes once weekly on days 1, 8, and 15, and courses repeating
every 28 days) will continue on the 4-week schedule.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of ABT-888 and gemcitabine hydrochloride, determined according to incidence of DLT graded using the NCI CTCAE version 4.0
University of Pittsburgh
United States: Food and Drug Administration
|University of Pittsburgh||Pittsburgh, Pennsylvania 15261|
|UPMC Hillman Cancer Center||Pittsburgh, Pennsylvania 15232|
|Penn State Milton S Hershey Medical Center||Hershey, Pennsylvania 17033|
|Magee-Womens Hospital - University of Pittsburgh Medical Center||Pittsburgh, Pennsylvania 15213|