A Trial of Dalotuzumab in Combination With Irinotecan Versus Cetuximab and Irinotecan for Participants With Metastatic Rectal Cancers (mRC) (MK-0646-025)
- Conditions
- Rectal Neoplasms
- Interventions
- Registration Number
- NCT01609231
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 11
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Dalotuzumab + Irinotecan 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). Arm B: Cetuximab + Irinotecan 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). Arm B: Cetuximab + Irinotecan Cetuximab 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). Arm A: Dalotuzumab + Irinotecan Dalotuzumab 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).
- Primary Outcome Measures
Name Time Method Assessment of Progression-free Survival (PFS) 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) 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.
- Secondary Outcome Measures
Name Time Method 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) 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.