A Dose Finding Study Followed by Phase II Randomized, Placebo-Controlled Study of Veliparib (ABT-888) Added to Chemoradiotherapy With Carboplatin and Paclitaxel for Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC)
I. To establish the maximum tolerated dose (MTD) and the recommended phase II dose of
ABT-888 (veliparib) when given concurrently with standard carboplatin/paclitaxel and
radiotherapy in patients with unresectable stage III non-small cell lung cancer (NSCLC).
(Phase I) II. To assess whether carboplatin/paclitaxel plus ABT-888 compared with
carboplatin/paclitaxel plus placebo improves progression-free survival (PFS) in patients
with unresectable stage III NSCLC. (Phase II) III. To compare overall survival (OS) in
patients treated with carboplatin/paclitaxel and radiotherapy plus ABT-888 to those treated
with carboplatin, paclitaxel and radiotherapy plus placebo. (Phase II) IV. To assess the
response rate (confirmed and unconfirmed, complete and partial responses) and disease
control rate in the subset of patients with measurable disease by Response Evaluation
Criteria in Solid Tumors (RECIST) criteria. (Phase II) V. To assess the safety and toxicity
profile of the regimen. (Phase II)
I. To collect tumor tissue from pretreatment biopsies (archival samples) for biomarker
studies, including poly (ADP-ribose) polymerase 1 (PARP) activity by measuring the levels of
poly-ADP-ribose, gamma-H2A histone family, member X (y-H2AX), and messenger ribonucleic acid
(mRNA) expression levels of deoxyribonucleic acid (DNA) repair enzymes such as excision
repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC1)/X-ray
repair complementing defective repair in Chinese hamster cells 1 (XRCC1).
II. To collect blood samples for evaluation of y-H2AX (circulating tumor cells) and other
relevant future studies.
OUTLINE: This is a multicenter, dose-escalation study of veliparib followed by a randomized
phase II study.
INDUCTION THERAPY: Patients undergo 3D-conformal radiotherapy (RT) once daily, 5 days a
week, for 7 weeks. Patients also receive veliparib orally (PO) twice daily (BID) on days
1-50 and carboplatin intravenously (IV) over 30 minutes and paclitaxel IV over 1 hour on
days 1, 8, 15, 22, 20, 36, and 43 in the absence of disease progression or unacceptable
toxicity. Patients without disease progression after completion of chemoradiotherapy undergo
CONSOLIDATION THERAPY: Beginning within 4-6 weeks of chemoradiotherapy, patients receive
veliparib PO BID on days 1-7 and carboplatin IV over 30 minutes and paclitaxel IV over 3
hours on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease
progression or unacceptable toxicity.
PHASE II: Patients are stratified according to Eastern Cooperative Oncology Group (ECOG)
performance status (0 vs 1), weight-loss in previous 3 months (=< 5% vs > 5%), and age (=<
65 vs > 65). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo RT and receive veliparib, carboplatin, and paclitaxel as in phase I
induction and consolidation therapy.
ARM II: Patients undergo RT as in arm I. Patients also receive placebo PO BID on days 1-50
and carboplatin and paclitaxel as in arm I. Within 4-6 weeks after completion of
chemoradiotherapy, patients receive placebo on days 1-7 and carboplatin and paclitaxel as in
Blood and archived tumor tissue samples are collected for biomarker studies. Bronchoscopic
tissue samples may also be collected.
After completion of study therapy, patients are followed up every 4 months for 2 years and
then every 6 months for 3 years.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of veliparib when given concurrently with standard carboplatin/paclitaxel and radiotherapy, determined according to incidence of dose limiting toxicity (DLT) graded using NCI CTCAE version 4.0 (Phase I)
Southwest Oncology Group
United States: Food and Drug Administration
|University of Texas Health Science Center at San Antonio||San Antonio, Texas 78284-7811|
|Central Illinois Hematology Oncology Center||Springfield, Illinois 62701|
|City of Hope Medical Center||Duarte, California 91010|
|City of Hope||Duarte, California 91010|
|Tower Cancer Research Foundation||Beverly Hills, California 90211|
|Wayne State University||Detroit, Michigan 48202|
|UC Davis Comprehensive Cancer Center||Sacramento, California 95817|
|Illinois CancerCare-Peoria||Peoria, Illinois 61615|
|Fort Wayne Medical Oncology and Hematology Inc - State Boulevard||Fort Wayne, Indiana 46845|
|Cancer Therapy and Research Center at The UT Health Science Center at San Antonio||San Antonio, Texas 78229|
|Audie L Murphy Veterans Affairs Hospital||San Antonio, Texas 78209|
|University Hospital||San Antonio, Texas 78229|