A Phase 2 Randomized Open-Label Study Of Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy In Previously Treated KRAS Mutation Positive Subjects With Locally Advanced Or Metastatic Nonâ??Small Cell Lung Cancer.
The primary objective of this study is to evaluate progressionfree survival (PFS) among subjects with KRAS mutation positive NSCLC treated with erlotinib plus ARQ 197 compared to single agent chemotherapy. Secondary objectives include: 1. To evaluate overall survival (OS) among all eligible subjects treated with erlotinib plus ARQ 197 compared to chemotherapy. 2. To determine the objective response rate (ORR) among all eligible subjects treated with erlotinib plus ARQ 197 compared to chemotherapy. 3. To determine the objective response rate (ORR) among subjects randomly assigned to chemotherapy who cross over following disease progression to receive erlotinib plus ARQ 197 and who are evaluable for a post-progression scan on crossover therapy. 4. To further characterize the safety of ARQ 197 in combination with erlotinib in subjects with KRAS mutation positive NSCLC. An exploratory objective of this study includes assessment of quality of life with the use of the Functional Assessment of Cancer Therapy-Lung scale (analysis will be reported separately from the main study report).
Eligible subjects will be randomly assigned to receive erlotinib plus ARQ 197 (EA arm) or single agent chemotherapy (C arm). Adult subjects with inoperable locally advanced or metastatic (stage IVA/IVB) NSCLC with measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)Version 1.1 criteria, are eligible. Subjects must have received at least one prior chemotherapy regimen (except prior EGFR inhibitor, c-MET inhibitor, or all three chemotherapy agents selected for administration in this study). In this study, cancer staging will follow the American Joint Committee on Cancerï¿½s AJCC Cancer Staging Manual, 7th ed.
Subjects will receive one of two following treatments: ARQ 197 administered PO, with meals, as 360 mg (3 x 120mg capsules or tablets) twice daily (i.e., once in the morning and once in the evening); plus erlotinib 150 mg administered PO once daily, at least 1 hour prior to and at least 2 hours after the ingestion of food, or one single agent chemotherapy (investigatorï¿½s choice of one: pemetrexed, docetaxel, or gemcitabine) administered per approved labeling (package insert). The primary efficacy endpoint of the study is median PFS in the ITT population treated with erlotinib plus ARQ 197 compared to chemotherapy.
05/24/2013 04:02 AM