Clinical trial NCT00614393: Study of Dalotuzumab (MK-0646) in Combination With Cetuximab and Irinotecan in Metastatic Colorectal Cancer (MK-0646-004)
Official title: A Phase II/III Study of Dalotuzumab (MK-0646) Treatment in Combination With Cetuximab and Irinotecan for Patients With Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Colorectal Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-02-13
Enrollment: 558
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 12 weeks after last dose of study drug (Up to 35 months)
measure: Progression-free Survival (PFS)
timeFrame: Up to last dose of study drug (Up to 32 months)
measure: Percentage of Participants Who Have a Clinical or Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 to 5 Toxicity
timeFrame: Up to 30 days after last dose of study drug (Up to 33 months)
measure: Percentage of Participants Who Have a Drug-related Clinical or Laboratory CTCAE Grade 3 to 5 Toxicity
timeFrame: Up to 30 days after last dose of study drug (Up to 33 months)
measure: Percentage of Participants Who Discontinue Study Drug Due to an AE
timeFrame: Up to last dose of study drug (Up to 32 months)
measure: Percentage of Participants Who Experience an AE of Infusion Site Reaction
timeFrame: Up to 30 days after last dose of study drug (Up to 33 months)
Secondary outcomes:
measure: Overall Response Rate (ORR) of Dalotuzumab in Combination With Cetuximab + Irinotecan Versus ORR of Cetuximab + Irinotecan Alone in Participants With Wild Type of Colorectal Cancer
timeFrame: Every 6 weeks (Up to 32 months)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Sclafani F, Kim TY, Cunningham D, Kim TW, Tabernero J, Schmoll HJ, Roh JK, Kim SY, Park YS, Guren TK, Hawkes E, Clarke SJ, Ferry D, Frodin JE, Ayers M, Nebozhyn M, Peckitt C, Loboda A, Mauro DJ, Watkins DJ. A Randomized Phase II/III Study of Dalotuzumab in Combination With Cetuximab and Irinotecan in Chemorefractory, KRAS Wild-Type, Metastatic Colorectal Cancer. J Natl Cancer Inst. 2015 Sep 23;107(12):djv258. doi: 10.1093/jnci/djv258. Print 2015 Dec.