Clinical trial NCT00614393
Conditions: Metastatic Colorectal Cancer
Sponsor: Merck Sharp & Dohme LLC
Start date: 2007-12-24; Completion date: 2012-03-07
Enrollment: 558 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will compare the safety and efficacy of dalotuzumab (MK-0646) in combination with cetuximab and irinotecan in treating participants with wild type KRAS (wtKRAS) metastatic colorectal cancer (CRC) compared to cetuximab and irinotecan alone.

The primary study hypothesis is that administration of dalotuzumab in combination with cetuximab and irinotecan to participants with metastatic CRC expressing the wtKRAS genotype improves Overall Survival OR Progression-free Survival compared to participants treated with cetuximab and irinotecan alone.

Detailed description:
Dalotuzumab is a humanized monoclonal antibody (mAb) that targets the insulin-like growth factor type 1 receptor-1 (IGF-1R). Dalotuzumab may act through inhibition of insulin-like growth factor-1 (IGF-1)-mediated cell signaling to cause reductions in tumor growth and spread antibody dependent cell-mediated cytotoxicity.

In preclinical studies, dalotuzumab improved the activity of an anti-epidermal growth factor receptor (EGFR) mAb and the activity of erlotinib, a small molecule inhibitor of EGFR.

All eligible participants will receive cetuximab 400 mg/m\^2 infusion over 120 minutes followed by weekly infusions of cetuximab 250 mg/m\^2 over 60-120 minutes along with irinotecan infusion over 30-90 minutes. Dosage of irinotecan will be the same as most recent pre-study therapy. Participants will then be assigned to one of three treatment double-blind arms.

Arms: arm 1: In double-blind (DB) Week 1, participants receive cetuximab 400 mg/m\^2 intravenously (IV) loading dose and irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants receive cetuximab 250 mg/m\^2 IV one time each week (Q1W) maintenance dose, irinotecan IV Q1W and DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment. arm 2: In the open-label (OL) portion of the study, ≥6 participants receive cetuximab 400 mg/m\^2 Q1W + irinotecan Q1W at their pre-study dosage + OL dalotuzumab (loading dose of 15 mg/kg IV followed by a maintenance dose of 7.5 mg/kg 2 weeks later) to verify the safety of the regimen. In DB Week 1, participants receive cetuximab 400 mg/m\^2 IV + irinotecan IV. In DB Week 2, participants receive cetuximab 250 mg/m\^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants receive cetuximab 250 mg/m\^2 IV + irinotecan IV. Starting with DB Week 4, participants receive cetuximab 250 mg/m\^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV Q2W for up to 32 months of treatment. arm 3: In the OL portion of the study, ≥6 participants receive cetuximab 400 mg/m\^2 Q1W+ irinotecan Q1W at their pre-study dosage + OL dalotuzumab 10 mg/kg IV Q1W to verify the safety of the regimen. In DB Week 1, participants receive cetuximab 400 mg/m\^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants receive cetuximab 250 mg/m\^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment. arm 4: In DB Week 1, participants receive cetuximab 400 mg/m\^2 IV + irinotecan IV at their pre-study dosage. In DB Week 2, participants receive cetuximab 250 mg/m\^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants receive cetuximab 250 mg/m\^2 IV + irinotecan IV. Starting with DB Week 4, participants receive cetuximab 250 mg/m\^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV Q2W for up to 32 months of treatment. arm 5: In DB Week 1, participants receive cetuximab 400 mg/m\^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants receive cetuximab 250 mg/m\^2 IV Q1W + irinotecan IV Q1W + DB normal saline (placebo) IV Q1W for up to 32 months of treatment.
Interventions: intervention 1: dalotuzumab intervention 2: irinotecan hydrochloride intervention 3: cetuximab intervention 4: placebo
Intervention descriptions: intervention 1: IV infusion intervention 2: IV infusion intervention 3: IV infusion intervention 4: IV infusion

Protocol documents: