Conditions: Metastatic Colorectal Cancer
Keywords: Colorectal cancer wild-type KRAS irinotecan cetuximab second-line therapy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 131
Healthy volunteers: no

Brief summary:
ARQ 197 or placebo in combination with irinotecan and cetuximab in participants with metastatic colorectal cancer (CRC), in participants with wild-type KRAS alleles who have failed front-line systemic therapy, to evaluate the safety, tolerability, and efficacy of ARQ 197, define the recommended dose for Phase 2.

After the recommended dose is determined for Phase 2, participants receive study drug or placebo with irinotecan and cetuximab.

Detailed description:
Phase 1/2 Multicenter study:

* Phase 1 portion is open-label to evaluate the safety of ARQ 197 administered in combination with irinotecan and cetuximab.
* Phase 2 portion is designed as a randomized, double-blind placebo-controlled study to assess the efficacy and safety of ARQ 197 or matching placebo administered in combination with irinotecan and cetuximab.

Arms:
arm 1: Tivantinib in combination with irinotecan and cetuximab. arm 2: Placebo in combination with irinotecan and cetuximab arm 3: Tivantinib in combination with irinotecan and cetuximab.

Interventions: intervention 1: Tivantinib intervention 2: Placebo intervention 3: Cetuximab intervention 4: Irinotecan
Intervention descriptions: intervention 1: ARQ 197 is supplied as a 120-mg capsule, administered twice daily at the dose determined in the Phase 1 portion of the study. Administered until disease progression, unacceptable toxicity or other discontinuation criteria is met. intervention 2: Placebo to match ARQ 197, administered twice daily. Administered until disease progression, unacceptable toxicity or other discontinuation criteria is met. intervention 3: Cetuximab 500 mg/ m\^2 intravenous infusion over 120 minutes at the first cycle, then over 60-minutes at subsequent cycles. Administered on Day 1 and Day 15 of each 28 day cycle. Administered until disease progression, unacceptable toxicity or other discontinuation criteria is met. intervention 4: 60 minutes after cetuximab, Irinotecan 180 mg/m\^2 intravenous infusion over 30 - 90 minutes. Administered on Day 1 and Day 15 of each 28 day cycle. Administered until disease progression, unacceptable toxicity or other discontinuation criteria is met.

Protocol document: