A Trial of Dalotuzumab in Combination With Irinotecan Versus Cetuximab and Irinotecan for Participants With Metastatic Rectal Cancers (mRC) (MK-0646-025 AM4)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01609231
First received: May 29, 2012
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

The purpose of this adaptive trial is to compare the progression-free survival of participants with metastatic rectal carcinoma when treated with dalotuzumab + irinotecan therapy relative to participants treated with cetuximab + irinotecan.


Condition Intervention Phase
Rectal Neoplasms
Drug: Dalotuzumab
Drug: Irinotecan
Drug: Cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IIA Open Label, Adaptive, Randomized Clinical Trial of Dalotuzumab (MK-0646) Treatment in Combination With Irinotecan Versus Cetuximab and Irinotecan for Patients With Metastatic Rectal Cancers (mRC) Expressing High IGF-1/Low IGF-2 Levels

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: From randomization (Cycle 1 Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to approximately 3 years) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Objective Response Rate [ Time Frame: From randomization (Cycle 1 Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to approximately 3 years) ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: July 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Dalotuzumab + Irinotecan Drug: Dalotuzumab
Dalotuzumab will be administered intravenously after the completion of irinotecan infusion at a dose of 10 mg/kg once weekly.
Other Name: MK-0646
Drug: Irinotecan
Irinotecan 180 mg/m^2 will be administered intravenously once every two weeks either prior to dalotuzumab (Arm A) or after cetuximab (Arm B). Pre-medication at the discretion of the investigator, such as with dexamethasone or atropine will follow local, or country-specific standard of care.
Other Name: Camptosar
Active Comparator: Arm B: Cetuximab + Irinotecan Drug: Irinotecan
Irinotecan 180 mg/m^2 will be administered intravenously once every two weeks either prior to dalotuzumab (Arm A) or after cetuximab (Arm B). Pre-medication at the discretion of the investigator, such as with dexamethasone or atropine will follow local, or country-specific standard of care.
Other Name: Camptosar
Drug: Cetuximab
Cetuximab will be administered intravenously prior to irinotecan at an initial dose of 400 mg/m^2 followed by weekly infusions of 250 mg/m^2. Pre-medication at the discretion of the investigator, such as with a histamine receptor antagonist or corticosteroid, will follow local, or country-specific standard of care.
Other Name: Erbitux

  Eligibility

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

Inclusion Criteria:

  • Metastatic colorectal cancer with primary tumor originating from the

rectum

  • Available archival (recent or remote) tumor, or newly obtained formalin-fixed tissue available for analysis for biomarker studies
  • At least one measurable lesion greater than or equal to 10 mm
  • Disease has progressed after treatment with both irinotecan and oxaliplatin

containing regimens and should have progressed on or within 3 months of completing their last line of therapy

  • Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale

Exclusion Criteria:

  • Known diabetic who is poorly controlled
  • Chemotherapy or biological therapy within 2 weeks prior to initial dosing on this study, or whose toxicities from agents administered 2 weeks earlier have not resolved to at least grade 1 or baseline, or who is within 3 weeks from

a prior surgery

  • Radiotherapy within 2 weeks prior to initial dosing on this study, unless the radiotherapy was for management of pain
  • Currently participating or has participated in a study with an investigational compound or device within 30 days or 5 half-lives of the investigational agent, whichever is longer, of initial dosing on this study
  • Could not complete previous course of irinotecan due to intolerable toxicity, other than discontinuation due to fatigue following prolonged administration (>4 months exposure)
  • Prior exposure to insulin-like growth factor 1 receptor (IGF-1R) inhibitors or epidermal growth factor receptor (EGFR) inhibitors
  • Known Central Nervous System (CNS) metastases and/or carcinomatous meningitis
  • Primary CNS tumor
  • History of a prior malignancy with the exception of cervical intraepithelial neoplasia; basal cell carcinoma of the skin; adequately treated localized prostate carcinoma; potentially curative therapy with no evidence of that disease for 5 years, deemed low risk for recurrence by treating physician.
  • Human Immunodeficiency Virus (HIV)-positive
  • Active Hepatitis B or C receiving antiviral treatment regimens
  • Symptomatic ascites or pleural effusion
  • Concurrently using growth hormone (GH), or growth hormone inhibitors
  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: NCT01609231     History of Changes
Other Study ID Numbers: 0646-025, 2012-000317-36
Study First Received: May 29, 2012
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Irinotecan
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 20, 2014