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

NCT ID: NCT01609231

Last Updated: 2020-05-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-06
• Study Completion Date: 2014-12-09

Brief Summary

The purpose of this adaptive trial is to compare the progression-free survival of participants with metastatic rectal carcinoma when treated with intravenous (IV) dalotuzumab (MK-0646) + irinotecan therapy relative to participants treated with IV cetuximab + irinotecan. The primary hypothesis is that administration of dalotuzumab in combination with irinotecan to participants with wild-type KRAS metastatic rectal carcinoma with high insulin growth factor (IGF)-1/low IGF-2 expression levels improves progression-free survival compared to patients treated with cetuximab in combination with irinotecan.

Conditions

Rectal Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: Dalotuzumab + Irinotecan

Participants receive irinotecan intravenously (IV), 180 mg/m\^2 once every two weeks + dalotuzumab IV, 10 mg/kg once weekly, during ≥1 42-day treatment cycle(s).

Group Type: EXPERIMENTAL

Dalotuzumab

Intervention Type: DRUG

Dalotuzumab will be administered intravenously after the completion of irinotecan infusion at a dose of 10 mg/kg once weekly.

Irinotecan

Intervention Type: DRUG

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 will follow local or country-specific standard of care.

Arm B: Cetuximab + Irinotecan

Participants receive cetuximab IV, initial dose of 400 mg/m\^2 and then 250 mg/m\^2 IV weekly + irinotecan IV, 180 mg/m\^2 once every two weeks, during ≥1 42-day treatment cycle(s).

Group Type: ACTIVE_COMPARATOR

Irinotecan

Intervention Type: DRUG

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 will follow local or country-specific standard of care.

Cetuximab

Intervention Type: DRUG

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 will follow local or country-specific standard of care.

Interventions

Dalotuzumab

Dalotuzumab will be administered intravenously after the completion of irinotecan infusion at a dose of 10 mg/kg once weekly.

Intervention Type: 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 will follow local or country-specific standard of care.

Intervention Type: 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 will follow local or country-specific standard of care.

Intervention Type: DRUG

Other Intervention Names

MK-0646; Camptosar; Erbitux

Eligibility Criteria

Inclusion Criteria

• Has metastatic colorectal cancer with primary tumor originating from the rectum
• Has an available archival (recent or remote) tumor, or newly obtained formalin-fixed tissue available for analysis for biomarker studies
• Has 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
• Has a performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale

Exclusion Criteria

• Has poorly-controlled diabetes
• Has received 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
• Has received radiotherapy within 2 weeks prior to initial dosing on this study, unless the radiotherapy was for management of pain
• Is 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
• Was unable to complete previous course of irinotecan due to intolerable toxicity, other than discontinuation due to fatigue following prolonged administration (>4 months exposure)
• Has prior exposure to insulin-like growth factor 1 receptor (IGF-1R) inhibitors or epidermal growth factor receptor (EGFR) inhibitors
• Has a known central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has primary CNS tumor
• Has a 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.
• Is human immunodeficiency virus (HIV)-positive
• Has active hepatitis B or C infection and is receiving antiviral treatment regimens
• Has symptomatic ascites or pleural effusion
• Is concurrently using growth hormone (GH), or growth hormone inhibitors

• 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

Other Identifiers

2012-000317-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-0646-025

Identifier Type: OTHER

Identifier Source: secondary_id

0646-025

Identifier Type: -

Identifier Source: org_study_id