Study of Dalotuzumab (MK-0646) in Combination With Cetuximab and Irinotecan in Metastatic Colorectal Cancer (MK-0646-004)

A Phase II/III Study of Dalotuzumab (MK-0646) Treatment in Combination With Cetuximab and Irinotecan for Patients With Metastatic Colorectal Cancer

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.

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.

Inclusion Criteria:

• Participant must have confirmed wtKRAS CRC.
• Participant must have previously failed both irinotecan and oxaliplatin containing regimens, and should have progressed on or within 3 months of completing their last line of therapy with objective evidence of progression as verified by previous radiologic scans.

Exclusion Criteria:

• Participant has had cancer treatment within 2 weeks before the first dose of study drug(s) or if the side effects from the drugs have not gone down to a certain level 2 weeks before the first dose of study drugs.
• Participant has had a bad side effect to irinotecan therapy.
• Participant has human immunodeficiency virus (HIV).
• Participant has Hepatitis B or C.
• Participant is pregnant or breast feeding or planning to have a child while on this study.