Study of Dalotuzumab (MK0646) in Combination With Cetuximab and Irinotecan in Metastatic Colorectal Cancer (MK-0646-004 AM9)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00614393
First received: January 17, 2008
Last updated: April 9, 2012
Last verified: April 2012
  Purpose

This study will compare how well dalotuzumab in combination with cetuximab and irinotecan works in treating patients with wild type KRAS metastatic colorectal cancer compared to how well cetuximab and irinotecan work alone.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: dalotuzumab
Drug: irinotecan hydrochloride
Drug: cetuximab
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Phase II III Study of MK0646 Treatment in Combination With Cetuximab and Irinotecan For Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Overall survival. [ Time Frame: Every three months ] [ Designated as safety issue: No ]
  • Progression-free survival. [ Time Frame: Every three months ] [ Designated as safety issue: No ]
  • Percentage of patients that have clinical or laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 to 5 toxicity [ Time Frame: 30 days after last dose of study medication ] [ Designated as safety issue: Yes ]
  • Percentage of patients that have drug related clinical or laboratory CTCAE Grade 3 to 5 toxicity [ Time Frame: 30 days after last dose of study medication ] [ Designated as safety issue: Yes ]
  • Percentage of patients that discontinue study therapy due to adverse event (AE) [ Time Frame: 30 days after last dose of study medication ] [ Designated as safety issue: Yes ]
  • Percentage of patients that have a dose modification due to AE [ Time Frame: 30 days after last dose of study medication ] [ Designated as safety issue: Yes ]
  • Percentage of patients that experience infusion reactions [ Time Frame: 30 days after last dose of study medication ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Objective response rate of dalotuzumab in combination with Cetuximab (+) Irinotecan versus objective response rate of Cetuximab (+) Irinotecan alone in patients with wild type of colorectal cancer [ Time Frame: Every three months ] [ Designated as safety issue: No ]

Enrollment: 560
Study Start Date: December 2007
Study Completion Date: March 2012
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A: Dalotuzumab 10 mg/kg Drug: dalotuzumab
Dalotuzumab 7.5 mg/kg infusion over 60-120 minutes; Dalotuzumab 10 mg/kg infusion over 60-120 minutes; Dalotuzumab 15 mg/kg infusion over 60-120 minutes.
Other Name: MK-0646
Drug: irinotecan hydrochloride
Dosage of irinotecan will be the same as most recent pre-study therapy
Drug: cetuximab
Dosage of cetuximab 400 mg/m2 infusion over 120 minutes followed by weekly infusions of 250 mg/m2 over 60 minutes.
Experimental: B: Dalotuzumab 15 mg/kg Drug: dalotuzumab
Dalotuzumab 7.5 mg/kg infusion over 60-120 minutes; Dalotuzumab 10 mg/kg infusion over 60-120 minutes; Dalotuzumab 15 mg/kg infusion over 60-120 minutes.
Other Name: MK-0646
Drug: irinotecan hydrochloride
Dosage of irinotecan will be the same as most recent pre-study therapy
Drug: cetuximab
Dosage of cetuximab 400 mg/m2 infusion over 120 minutes followed by weekly infusions of 250 mg/m2 over 60 minutes.
Active Comparator: C: Dalotuzumab placebo Drug: irinotecan hydrochloride
Dosage of irinotecan will be the same as most recent pre-study therapy
Drug: cetuximab
Dosage of cetuximab 400 mg/m2 infusion over 120 minutes followed by weekly infusions of 250 mg/m2 over 60 minutes.
Drug: Placebo
placebo to dalotuzumab, infusion over 60-120 minutes once weekly.

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/m2 infusion over 120 minutes followed by weekly infusions of 250 mg/m2 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 3 treatment arms.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • You must have confirmed KRAS wild type colorectal cancer.
  • You must have previously failed both irinotecan and oxaliplatin containing regimens, and should have progressed on or within 3 months of completing your last line of therapy with objective evidence of progression as verified by previous radiologic scans.

Exclusion Criteria:

  • You have 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.
  • You have had a bad side effect to irinotecan therapy.
  • You have human immunodeficiency virus (HIV).
  • You have Hepatitis B or C.
  • You are pregnant or breast feeding or planning to have a child while on this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00614393     History of Changes
Other Study ID Numbers: MK-0646-004, 2007_529
Study First Received: January 17, 2008
Last Updated: April 9, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
Camptothecin
Cetuximab
Antibodies, Monoclonal
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunologic Factors

ClinicalTrials.gov processed this record on July 22, 2014