Phase I and Randomized Phase II Double Blind Clinical Trial of Cisplatin and Etoposide in Combination With Veliparib (ABT-888) or Placebo as Frontline Therapy for Extensive Stage Small Cell Lung Cancer
I. To determine the recommended phase II dose (RP2D) of veliparib to use in combination with
CE. (Phase I) II. To determine whether the addition of ABT-888 (veliparib) to cisplatin
etoposide (CE) results in improved progression free survival (PFS) over CE with placebo in
the frontline therapy of newly diagnosed extensive stage small cell lung cancer. (Phase II)
I. To determine the overall survival (OS) associated with the combination of CE plus
ABT-888. (Phase II) II. To assess the overall response rate (ORR) as well as complete
response rate (CRR) associated with the combination of CE plus ABT-888. (Phase II) III. To
determine the toxicity profile of the combination of ABT-888 and CE chemotherapy in this
patient population. (Phase II) IV. To conduct exploratory correlative analysis of the impact
of select biomarkers. (Phase II) V. To compare the overall toxicity profile and specifically
the incidence and severity of chemotherapy-induced peripheral neuropathy with the addition
of ABT-888 to CE. (Phase II)
OUTLINE: This is a phase I, dose-escalation study of veliparib followed by a phase II,
randomized, double-blind study.
Phase I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7, etoposide
intravenously (IV) over 60-120 minutes on days 1-3, and cisplatin IV over 60-120 minutes on
day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression
or unacceptable toxicity.
Phase II: Patients are stratified according to gender (male vs female) and lactate
dehydrogenase (LDH) (=< ULN vs > ULN. Patients are randomized to 1 of 2 treatment arms.
Arm A: Patients receive veliparib PO BID on days 1-7, etoposide IV over 60-120 minutes on
days 1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for
4 courses in the absence of disease progression or unacceptable toxicity.
Arm B: Patients receive placebo PO BID on days 1-7, etoposide IV over 60-120 minutes on days
1-3, and cisplatin IV over 60-120 minutes on day 1. Treatment repeats every 21 days for 4
courses in the absence of disease progression or unacceptable toxicity.
Peripheral blood mononuclear cells and tumor tissue samples may be collected periodically
for correlative studies.
After completion of study treatment, patients are followed up periodically for 3 years.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum-tolerated dose of veliparib based on the incidence of dose-limiting toxicity as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
|Johns Hopkins University||Baltimore, Maryland 21205|
|Fox Chase Cancer Center||Philadelphia, Pennsylvania 19111|
|Abramson Cancer Center of the University of Pennsylvania||Philadelphia, Pennsylvania 19104-4283|
|Ingalls Memorial Hospital||Harvey, Illinois 60426|
|Cancer Institute of New Jersey||New Brunswick, New Jersey 08901|
|Cancer Institute of New Jersey at Hamilton||Hamilton, New Jersey 08690|
|Paoli Memorial Hospital||Paoli, Pennsylvania 19301-1792|
|Parkland Memorial Hospital||Dallas, Texas 75235|
|Bryn Mawr Hospital||Bryn Mawr, Pennsylvania 19010|
|Trinity Medical Center||Moline, Illinois 61265-1291|
|Emory University||Atlanta, Georgia 30322|
|University of Texas Southwestern Medical Center||Dallas, Texas|
|Lankenau Hospital||Wynnewood, Pennsylvania 19096|
|Penn State Milton S Hershey Medical Center||Hershey, Pennsylvania 17033|
|Mainline Health CCOP||Wynnewood, Pennsylvania 19096|
|Eastern Cooperative Oncology Group||Boston, Massachusetts 02215|