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

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

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.

Study Overview

• Status: Terminated
• Conditions: Rectal Neoplasms
• Intervention / Treatment: Drug: Dalotuzumab; Drug: Irinotecan; Drug: Cetuximab

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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).	Drug: Dalotuzumab; Dalotuzumab will be administered intravenously after the completion of irinotecan infusion at a dose of 10 mg/kg once weekly.; Other Names: 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 will follow local or country-specific standard of care.; Other Names: Camptosar
ACTIVE_COMPARATOR: 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).	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.; Other Names: 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 will follow local or country-specific standard of care.; Other Names: Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Progression-free Survival (PFS)	PFS is a measure of the time from randomization to the time of first documented disease progression (assessed by an independent Radiology Review Committee [iRRC]) or participant death, whichever occurs first.	From randomization (Cycle 1, Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to 3 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response Rate (ORR)	ORR is defined as the percentage of participants achieving a complete response (CR) or partial response (PR) during the course of the study using enhanced Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Confirmation of response was not required.	From randomization (Cycle 1, Day 1) to the first documented disease progression or death due to any cause, whichever occurs first (up to 3 years)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 6, 2012
• Primary Completion (ACTUAL): December 9, 2014
• Study Completion (ACTUAL): December 9, 2014

Study Registration Dates

• First Submitted: May 29, 2012
• First Submitted That Met QC Criteria: May 30, 2012
• First Posted (ESTIMATE): May 31, 2012

Study Record Updates

• Last Update Posted (ACTUAL): May 4, 2020
• Last Update Submitted That Met QC Criteria: April 21, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Topoisomerase I Inhibitors; Irinotecan; Cetuximab
• Other Study ID Numbers: 0646-025; 2012-000317-36 (EUDRACT_NUMBER); MK-0646-025 (OTHER: Merck Protocol Number)