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

NCT01609231 | Terminated Phase 2 Results

• 3 other identifiers: 0646-0252012-000317-36MK-0646-025
• Study Type: interventional
• Target: 11
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Percentage of Participants With Objective Response Rate (ORR)

  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)

Study Arms (2)

Arm A: Dalotuzumab + Irinotecan

EXPERIMENTAL

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; Drug: Irinotecan

Arm B: Cetuximab + Irinotecan

ACTIVE COMPARATOR

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; Drug: Cetuximab

Interventions

Dalotuzumab DRUG

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

Also known as: MK-0646

Arm A: Dalotuzumab + Irinotecan

Irinotecan 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.

Also known as: Camptosar

Arm A: Dalotuzumab + Irinotecan; Arm B: Cetuximab + Irinotecan

Cetuximab 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.

Also known as: Erbitux

Arm B: Cetuximab + Irinotecan

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

dalotuzumab; Irinotecan; Cetuximab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal 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

Limitations and Caveats

The study did not meet target enrollment and was terminated for business reasons; insufficient data were collected for efficacy analyses. Safety data are reported.

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2012
• First Posted: May 31, 2012
• Study Start: July 6, 2012
• Primary Completion: December 9, 2014
• Study Completion: December 9, 2014
• Last Updated: May 4, 2020
• Results First Posted: May 4, 2020

Record last verified: 2020-04