Neoplasms

Digestive System Diseases

All Conditions

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Irinotecan

Cetuximab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Topoisomerase I Inhibitors

Enzyme Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

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.

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.

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.

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.

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.

dalotuzumab

irinotecan hydrochloride

cetuximab

placebo

Medical Director

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.

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

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

The OS of participants with metastatic colorectal cancer (CRC) expressing the KRAS wild-type (wtKRAS) tumor genotype (indicating no detection of KRAS mutation) was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. OS was analyzed using the Kaplan-Meier method and is reported in months.

The PFS of participants with metastatic CRC expressing the wtKRAS genotype was defined as the time from the first day of study treatment to the first documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST 1.0) as documented by an independent core laboratory, or death due to any cause, whichever occurred first. Disease progression was defined as either a 20% or greater relative increase in the sum of diameters of target lesions OR an absolute increase of at least 5mm in the sum of lesions or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and is reported in months.

An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. (Grade 3=Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4=Life-threatening consequences; urgent intervention indicated. Grade 5=Death related to AE.) Participants were monitored for AEs until the earlier of study discontinuation or 30 days after dalotuzumab/placebo discontinuation. AE grades were assessed using the National Cancer Institute (NCI) CTCAE, version 3.0.

An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. (Grade 3=Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4=Life-threatening consequences; urgent intervention indicated. Grade 5=Death related to AE.) Drug-related AEs were those AEs that were possibly, probably, or definitely related to study drug or protocol-specified procedures. Participants were monitored for AEs related to dalotuzumab or placebo until the earlier of study discontinuation or 30 days after dalotuzumab/placebo discontinuation. AE grades were assessed using the NCI CTCAE, version 3.0.

An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure. The percentage of participants who discontinued study drug due to an AE is presented.

The percentage of participants who experienced an AE of infusion site reaction is presented.

ORR, using RECIST 1.0, was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR; disappearance of all target lesions) or Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) at any time during the study, based on central radiology review.

Merck Sharp & Dohme LLC

The APaT population consisted of all randomized participants who received ≥1 dose of study drug. Participants were included in the treatment group corresponding to the study drug they actually received.

In DB Week 1, participants received cetuximab 400 mg/m\^2 IV loading dose and irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m\^2 IV Q1W maintenance dose, irinotecan IV Q1W and DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment.

Dalotuzumab 10 mg/kg Q1W (BD)

In the OL portion of the study, ≥6 participants received 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 received cetuximab 400 mg/m\^2 IV + irinotecan IV. In DB Week 2, participants received cetuximab 250 mg/m\^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants received cetuximab 250 mg/m\^2 IV + irinotecan IV. Starting with DB Week 4, participants received 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.

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

In the OL portion of the study, ≥6 participants received 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 received cetuximab 400 mg/m\^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m\^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 10 mg/kg IV Q1W for up to 32 months of treatment.

Dalotuzumab 10 mg/kg Q1W (OL)

In DB Week 1, participants received cetuximab 400 mg/m\^2 IV + irinotecan IV at their pre-study dosage. In DB Week 2, participants received cetuximab 250 mg/m\^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants received cetuximab 250 mg/m\^2 IV + irinotecan IV. Starting with DB Week 4, participants received 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.

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

In DB Week 1, participants received cetuximab 400 mg/m\^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m\^2 IV Q1W + irinotecan IV Q1W + DB normal saline (placebo) IV Q1W for up to 32 months of treatment.

Placebo + Cetuximab + Irinotecan (DB)

Dalotuzumab 10 mg/kg Q1W (DB)

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

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

Total

Age, Continuous

Sex: Female, Male

The Baseline Analysis Population was the All Participants As Treated (APAT) population and consisted of all participants who received at least one dose of study drug.

Senior Vice President, Global Clinical Development

The Intent-to-Treat (ITT) population consisted of all participants who had a wtKRAS tumor genotype. The efficacy analyses were planned for and only included participants from the DB portion of the study. Participants from the OL portion were excluded from the analyses. Participants were counted in the group to which they were randomized.

Overall Survival (OS)

The ITT population consisted of all participants who had a wtKRAS tumor genotype. The efficacy analyses were planned for and only included participants from the DB portion of the study. Participants from the OL portion were excluded from the analyses. Participants were counted in the group to which they were randomized.

Progression-free Survival (PFS)

The All Participants as Treated (APaT) population consisted of all randomized participants who received ≥1 dose of study drug. Participants were included in the treatment group corresponding to the study drug they actually received.

Percentage of Participants Who Have a Clinical or Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 to 5 Toxicity

Percentage of Participants Who Have a Drug-related Clinical or Laboratory CTCAE Grade 3 to 5 Toxicity

Percentage of Participants Who Discontinue Study Drug Due to an AE

Percentage of Participants Who Experience an AE of Infusion Site Reaction

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

In double-blind (DB) Week 1, participants received cetuximab 400 mg/m\^2 intravenously (IV) loading dose and irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received 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.

In the open-label (OL) portion of the study, ≥6 participants received 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 received cetuximab 400 mg/m\^2 IV + irinotecan IV. In DB Week 2, participants received cetuximab 250 mg/m\^2 IV + irinotecan IV + DB dalotuzumab 15 mg/kg IV. In DB Week 3, participants received cetuximab 250 mg/m\^2 IV + irinotecan IV. Starting with DB Week 4, participants received cetuximab 250 mg/m\^2 IV Q1W + irinotecan IV Q1W + DB dalotuzumab 7.5 mg/kg IV one time every two weeks (Q2W) for up to 32 months of treatment.

In DB Week 1, participants received a cetuximab 400 mg/m\^2 IV + irinotecan IV at their pre-study dosage. Starting with DB Week 2, participants received cetuximab 250 mg/m\^2 IV Q1W + irinotecan IV Q1W + DB normal saline (placebo) IV Q1W for up to 32 months of treatment.

Spots Global Cancer Trial Database for Study of Dalotuzumab (MK-0646) in Combination With Cetuximab and Irinotecan in Metastatic Colorectal Cancer (MK-0646-004)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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