Back to resultsA Trial of Dalotuzumab in Combination With Irinotecan Versus Cetuximab and Irinotecan for Participants With Metastatic Rectal Cancers (mRC) (MK-0646-025)
Primary Purpose
Rectal Neoplasms
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Dalotuzumab
Irinotecan
Cetuximab
Sponsored by
About this trial
This is an interventional treatment trial for Rectal Neoplasms
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A: Dalotuzumab + Irinotecan
Arm B: Cetuximab + Irinotecan
Arm Description
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).
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).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01609231
Brief Title
A Trial of Dalotuzumab in Combination With Irinotecan Versus Cetuximab and Irinotecan for Participants With Metastatic Rectal Cancers (mRC) (MK-0646-025)
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
This trial was halted prematurely for business reasons and low enrollment.
Study Start Date
July 6, 2012 (Actual)
Primary Completion Date
December 9, 2014 (Actual)
Study Completion Date
December 9, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rectal Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: Dalotuzumab + Irinotecan
Arm Type
Experimental
Arm Description
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 Title
Arm B: Cetuximab + Irinotecan
Arm Type
Active Comparator
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Dalotuzumab
Other Intervention Name(s)
MK-0646
Intervention Description
Dalotuzumab will be administered intravenously after the completion of irinotecan infusion at a dose of 10 mg/kg once weekly.
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Other Intervention Name(s)
Camptosar
Intervention Description
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
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
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.
Primary Outcome Measure Information:
Title
Assessment of Progression-free Survival (PFS)
Description
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.
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 3 years)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Objective Response Rate (ORR)
Description
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.
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 3 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
A Trial of Dalotuzumab in Combination With Irinotecan Versus Cetuximab and Irinotecan for Participants With Metastatic Rectal Cancers (mRC) (MK-0646-025)
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