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

NCT ID: NCT00614393

Last Updated: 2018-08-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 558 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-24
• Study Completion Date: 2012-03-07

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Dalotuzumab 10 mg/kg Q1W (DB)

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.

Group Type: EXPERIMENTAL

dalotuzumab

Intervention Type: BIOLOGICAL

IV infusion

irinotecan hydrochloride

Intervention Type: DRUG

IV infusion

cetuximab

Intervention Type: BIOLOGICAL

IV infusion

Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (OL)

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.

Group Type: EXPERIMENTAL

dalotuzumab

Intervention Type: BIOLOGICAL

IV infusion

irinotecan hydrochloride

Intervention Type: DRUG

IV infusion

cetuximab

Intervention Type: BIOLOGICAL

IV infusion

Dalotuzumab 10 mg/kg Q1W (OL)

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.

Group Type: EXPERIMENTAL

dalotuzumab

Intervention Type: BIOLOGICAL

IV infusion

irinotecan hydrochloride

Intervention Type: DRUG

IV infusion

cetuximab

Intervention Type: BIOLOGICAL

IV infusion

Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (DB)

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.

Group Type: EXPERIMENTAL

dalotuzumab

Intervention Type: BIOLOGICAL

IV infusion

irinotecan hydrochloride

Intervention Type: DRUG

IV infusion

cetuximab

Intervention Type: BIOLOGICAL

IV infusion

Placebo + Cetuximab + Irinotecan (DB)

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.

Group Type: ACTIVE_COMPARATOR

irinotecan hydrochloride

Intervention Type: DRUG

IV infusion

cetuximab

Intervention Type: BIOLOGICAL

IV infusion

placebo

Intervention Type: DRUG

IV infusion

Interventions

dalotuzumab

IV infusion

Intervention Type: BIOLOGICAL

irinotecan hydrochloride

IV infusion

Intervention Type: DRUG

cetuximab

IV infusion

Intervention Type: BIOLOGICAL

placebo

IV infusion

Intervention Type: DRUG

Other Intervention Names

MK-0646; CAMPTOSAR®; ERBITUX®; placebo to dalotuzumab; normal saline solution

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: BACKGROUND

PMID: 26405092 (View on PubMed)

Other Identifiers

2007_529

Identifier Type: OTHER

Identifier Source: secondary_id

0646-004

Identifier Type: -

Identifier Source: org_study_id