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

NCT00614393 | Completed Phase 2 Results DMC

• 2 other identifiers: 0646-0042007_529
• Study Type: interventional
• Target: 558
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (6)

• Overall Survival (OS)

  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.

  Up to 12 weeks after last dose of study drug (Up to 35 months)

• Progression-free Survival (PFS)

  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.

  Up to last dose of study drug (Up to 32 months)

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

  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.

  Up to 30 days after last dose of study drug (Up to 33 months)

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

  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.

  Up to 30 days after last dose of study drug (Up to 33 months)

• Percentage of Participants Who Discontinue Study Drug Due to an AE

  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.

  Up to last dose of study drug (Up to 32 months)

• Percentage of Participants Who Experience an AE of Infusion Site Reaction

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

  Up to 30 days after last dose of study drug (Up to 33 months)

Secondary Outcomes (1)

• 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

  Every 6 weeks (Up to 32 months)

Study Arms (5)

Dalotuzumab 10 mg/kg Q1W (DB)

EXPERIMENTAL

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.

Biological: dalotuzumab; Drug: irinotecan hydrochloride; Biological: cetuximab

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

EXPERIMENTAL

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.

Biological: dalotuzumab; Drug: irinotecan hydrochloride; Biological: cetuximab

Dalotuzumab 10 mg/kg Q1W (OL)

EXPERIMENTAL

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.

Biological: dalotuzumab; Drug: irinotecan hydrochloride; Biological: cetuximab

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

EXPERIMENTAL

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.

Biological: dalotuzumab; Drug: irinotecan hydrochloride; Biological: cetuximab

Placebo + Cetuximab + Irinotecan (DB)

ACTIVE COMPARATOR

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.

Drug: irinotecan hydrochloride; Biological: cetuximab; Drug: placebo

Interventions

dalotuzumab BIOLOGICAL

IV infusion

Also known as: MK-0646

Dalotuzumab 10 mg/kg Q1W (DB); Dalotuzumab 10 mg/kg Q1W (OL); Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (DB); Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (OL)

irinotecan hydrochloride DRUG

IV infusion

Also known as: CAMPTOSAR®

Dalotuzumab 10 mg/kg Q1W (DB); Dalotuzumab 10 mg/kg Q1W (OL); Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (DB); Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (OL); Placebo + Cetuximab + Irinotecan (DB)

cetuximab BIOLOGICAL

IV infusion

Also known as: ERBITUX®

Dalotuzumab 10 mg/kg Q1W (DB); Dalotuzumab 10 mg/kg Q1W (OL); Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (DB); Dalotuzumab 15 mg/kg/7.5 mg/kg Q2W (OL); Placebo + Cetuximab + Irinotecan (DB)

placebo DRUG

IV infusion

Also known as: placebo to dalotuzumab, normal saline solution

Placebo + Cetuximab + Irinotecan (DB)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 26405092 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

dalotuzumab; Irinotecan; Cetuximab; Saline Solution

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2008
• First Posted: February 13, 2008
• Study Start: December 24, 2007
• Primary Completion: June 1, 2010
• Study Completion: March 7, 2012
• Last Updated: August 8, 2018
• Results First Posted: December 28, 2016

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share