Back to resultsPhase I Study of Dalotuzumab (MK-0646) in Combination With Cetuximab and Irinotecan in Participants With Colorectal Cancer (MK-0646-016)
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Dalotuzumab 10 mg/kg
Cetuximab
Irinotecan
Dalotuzumab 15/7.5 mg/kg
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- Is 20 years of Age or older
- Has a histologically or cytologically confirmed colorectal cancer
- Has previously failed both Irinotecan and Oxaliplatin containing regimens and should have progressed on or within 3 months of completing their last line of therapy with objective radiological evidence of progression as verified by previous radiologic scans
- Must have adequate organ function
Exclusion Criteria:
- Has had chemotherapy, radiotherapy, or biological therapy within 4 weeks prior to initial dosing on this study or whose toxicities from agents administrated 4 weeks earlier have not resolved to at least grade 1 or baseline
- Has experienced intolerable toxicity to Irinotecan therapy
- Has prior exposure to insulin-like growth factor 1 receptor (IGF-1R) inhibitors or epidermal growth factor receptor (EGFR) inhibitors (e.g. Cetuximab)
- Is concurrently using growth hormone (GH), Or GH inhibitors
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cetux/Irin - Dmab 10 mg/kg
Cetux/Irin - Dmab 15/7.5 mg/kg
Dmab 10 mg/kg - Cetux/Irin (DDI)
Arm Description
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in Cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1, 8, 15, 22, 29 and 36. Each cycle was 6 weeks long.
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Days 8, 22 and 36; followed in subsequent cycles by treatment with 7.5 mg/kg on Days 8, 22 and 36. Each cycle was 6 weeks long.
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For Drug-Drug Interaction (DDI). Each cycle was 6 weeks long.
Outcomes
Primary Outcome Measures
Number of Dose-limiting Toxicities (DLTs)
To be declared a DLT an adverse experience had a causality related to study therapy. DLTs could be adverse experiences possibly, probably, or definitely related to study therapy by the Investigator, and included the following : Grade 4 neutropenia lasting >= 5 days; Grade 3 or 4 neutropenia with fever >38.5°C; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity, except inadequately treated diarrhea, nausea and vomiting, rash, hyperglycemia, and transient abnormality of electrolytes. Anemia, infusion reactions, hypersensitivity reactions, and adverse experiences not-related to study therapy did not qualify as DLTs.
Number of Participants With an Adverse Event (AE)
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE.
Secondary Outcome Measures
Number of Participants With Human Anti-Human Antibody (HAHA)
Sera were collected from participants prior to administration of the first dose of study drug, every 6 weeks during the study period, then 4 weeks, 8 weeks and 12 weeks post-treatment. A sandwich format enzyme-linked immunosorbent assay (ELISA) was used to detect the presence of HAHA in serum.
Time to Maximum Concentration (Tmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone in or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Tmax of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Concentration at the End of Infusion (Ceoi) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Ceoi of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Maximum Concentration (Cmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Cmax of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Apparent Terminal Half-life (T1/2) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The T1/2 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Clearance From Plasma (CL) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The CL of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Steady-state Volume of Distribution (Vss) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Vss of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Area Under the Concentration-time Curve From 0-24 Hours Post-dose (AUC0-24) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The AUC0-24 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Area Under the Concentration-time Curve From 0-168 Hours Post-dose (AUC0-168) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The AUC0-168 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Tmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Tmax of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Cmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Cmax of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
T1/2 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The T1/2 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
CL of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The CL of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Vss of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Vss of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
AUC0-24 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The AUC0-24 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
AUC0-168 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The AUC0-168 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Tmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Tmax of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Cmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Cmax of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
T1/2 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The T1/2 of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29..
CL of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The CL of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Vss of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Vss of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
AUC0-24 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The AUC0-24 of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00925015
Brief Title
Phase I Study of Dalotuzumab (MK-0646) in Combination With Cetuximab and Irinotecan in Participants With Colorectal Cancer (MK-0646-016)
Official Title
A Phase I Study of MK-0646 in Combination With Cetuximab and Irinotecan in Patients With Advanced or Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
June 17, 2009 (Actual)
Primary Completion Date
July 28, 2010 (Actual)
Study Completion Date
December 6, 2010 (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 purposes of this study were to assess the safety, tolerability, pharmacokinetic interactions, and the Human Anti-Human Antibody of dalotuzumab in combination with cetuximab and irinotecan in participants with advanced or metastatic colorectal cancer in Japan.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cetux/Irin - Dmab 10 mg/kg
Arm Type
Experimental
Arm Description
After treatment with Cetuximab (Cetux) and Irinotecan (Irin), Dalotuzumab (Dmab) was administered as an intravenous infusion at 10 mg/kg in Cycle 1 on Days 22, 29 and 36; followed in subsequent cycles by treatment with 10 mg/kg on Days 1, 8, 15, 22, 29 and 36. Each cycle was 6 weeks long.
Arm Title
Cetux/Irin - Dmab 15/7.5 mg/kg
Arm Type
Experimental
Arm Description
After treatment with Cetux/Irin, Dmab was administered as an intravenous infusion at 15 mg/kg in Cycle 1 on Days 8, 22 and 36; followed in subsequent cycles by treatment with 7.5 mg/kg on Days 8, 22 and 36. Each cycle was 6 weeks long.
Arm Title
Dmab 10 mg/kg - Cetux/Irin (DDI)
Arm Type
Experimental
Arm Description
Dmab was administered in each cycle as an intravenous infusion at 10 mg/kg once weekly on Days 1, 22 and 29; followed by treatment with Cetux/Irin. For Drug-Drug Interaction (DDI). Each cycle was 6 weeks long.
Intervention Type
Biological
Intervention Name(s)
Dalotuzumab 10 mg/kg
Other Intervention Name(s)
MK-0646
Intervention Description
Dalotuzumab at 10 mg/kg was intravenously administered once weekly
Intervention Type
Biological
Intervention Name(s)
Cetuximab
Intervention Description
Following pre-treatment with a histamine-receptor antagonist, Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2, followed by subsequent once weekly intravenous infusions of 250 mg/m^2
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Irinotecan was administered with an intravenous infusion of 150 mg/m^2, once every other week for 42 days
Intervention Type
Biological
Intervention Name(s)
Dalotuzumab 15/7.5 mg/kg
Other Intervention Name(s)
MK-0646
Intervention Description
Dalotuzumab was intravenously administered, with the first infusion of 15 mg/kg, followed by subsequent infusions of 7.5 mg/kg
Primary Outcome Measure Information:
Title
Number of Dose-limiting Toxicities (DLTs)
Description
To be declared a DLT an adverse experience had a causality related to study therapy. DLTs could be adverse experiences possibly, probably, or definitely related to study therapy by the Investigator, and included the following : Grade 4 neutropenia lasting >= 5 days; Grade 3 or 4 neutropenia with fever >38.5°C; Grade 4 thrombocytopenia; Grade 3 or Grade 4 non-hematologic toxicity, except inadequately treated diarrhea, nausea and vomiting, rash, hyperglycemia, and transient abnormality of electrolytes. Anemia, infusion reactions, hypersensitivity reactions, and adverse experiences not-related to study therapy did not qualify as DLTs.
Time Frame
Four weeks of Cycle 1 treatment (up to 28 days)
Title
Number of Participants With an Adverse Event (AE)
Description
An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product, is also an AE.
Time Frame
Approximately 4 weeks after last drug treatment (up to Day 293)
Secondary Outcome Measure Information:
Title
Number of Participants With Human Anti-Human Antibody (HAHA)
Description
Sera were collected from participants prior to administration of the first dose of study drug, every 6 weeks during the study period, then 4 weeks, 8 weeks and 12 weeks post-treatment. A sandwich format enzyme-linked immunosorbent assay (ELISA) was used to detect the presence of HAHA in serum.
Time Frame
Up to 12 weeks after the last administration of dalotuzumab (up to 349 days)
Title
Time to Maximum Concentration (Tmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone in or in Combination With Cetuximab / Irinotecan
Description
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Tmax of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Time Frame
Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Title
Concentration at the End of Infusion (Ceoi) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Description
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Ceoi of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Time Frame
Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Title
Maximum Concentration (Cmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Description
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Cmax of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Time Frame
Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Title
Apparent Terminal Half-life (T1/2) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Description
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The T1/2 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Time Frame
Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Title
Clearance From Plasma (CL) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Description
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The CL of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Time Frame
Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Title
Steady-state Volume of Distribution (Vss) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Description
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The Vss of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Time Frame
Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Title
Area Under the Concentration-time Curve From 0-24 Hours Post-dose (AUC0-24) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Description
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The AUC0-24 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Time Frame
Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8 and 24 h after initiation of dalotuzumab infusion
Title
Area Under the Concentration-time Curve From 0-168 Hours Post-dose (AUC0-168) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
Description
In Cycle 1 Dalotuzumab was administered on Days 1 and 22 as an intravenous infusion at 10 mg/kg. In the same Cycle 1 Cetuximab was administered on Days 8, 15, 22 and 29; and Irinotecan was administered on Days 8 and 22. The AUC0-168 of plasma Dalotuzumab alone was determined on Day 1, and in combination with cetuximab/irinotecan on Day 22.
Time Frame
Cycle 1: Day 1 and Day 22 at predose, 0.5 h after start of infusion, end of infusion, 5, 8, 24, 30, 48, 96 and 168 h after initiation of dalotuzumab infusion
Title
Tmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Tmax of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Title
Cmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Cmax of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Title
T1/2 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The T1/2 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Title
CL of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The CL of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Title
Vss of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The Vss of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Title
AUC0-24 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The AUC0-24 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8 and 24 h after initiation of cetuximab infusion
Title
AUC0-168 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Cetuximab was administered with an initial intravenous infusion of 400 mg/m^2 on Day 8, followed by subsequent once weekly intravenous infusions of 250 mg/m^2 on Days 15, 22, 29 and 36. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Irinotecan was administered on Days 1, 22, and 29. The AUC0-168 of plasma Cetuximab was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
Title
Tmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Tmax of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
Title
Cmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Cmax of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
Title
T1/2 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The T1/2 of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29..
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
Title
CL of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The CL of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
Title
Vss of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The Vss of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
Title
AUC0-24 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
Description
In Cycle 1 Irinotecan was administered with an intravenous infusion of 150 mg/m^2 once every other week on Days 1, 15, and 29. In the same Cycle 1 Dalotuzumab 10 mg/kg was administered on Days 22, 29 and 36; and Cetuximab was administered on Days 1, 8, 15, 22, 29 and 36. The AUC0-24 of plasma Irinotecan was determined alone on Day 15 and in combination with dalotuzumab on Day 29.
Time Frame
Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8 and 24 h after completion of Irinotecan infusion
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Is 20 years of Age or older
Has a histologically or cytologically confirmed colorectal cancer
Has previously failed both Irinotecan and Oxaliplatin containing regimens and should have progressed on or within 3 months of completing their last line of therapy with objective radiological evidence of progression as verified by previous radiologic scans
Must have adequate organ function
Exclusion Criteria:
Has had chemotherapy, radiotherapy, or biological therapy within 4 weeks prior to initial dosing on this study or whose toxicities from agents administrated 4 weeks earlier have not resolved to at least grade 1 or baseline
Has experienced intolerable toxicity to Irinotecan therapy
Has prior exposure to insulin-like growth factor 1 receptor (IGF-1R) inhibitors or epidermal growth factor receptor (EGFR) inhibitors (e.g. Cetuximab)
Is concurrently using growth hormone (GH), Or GH 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
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
23921573
Citation
Doi T, Muro K, Yoshino T, Fuse N, Ura T, Takahari D, Feng HP, Shimamoto T, Noguchi K, Ohtsu A. Phase 1 pharmacokinetic study of MK-0646 (dalotuzumab), an anti-insulin-like growth factor-1 receptor monoclonal antibody, in combination with cetuximab and irinotecan in Japanese patients with advanced colorectal cancer. Cancer Chemother Pharmacol. 2013 Sep;72(3):643-52. doi: 10.1007/s00280-013-2240-8. Epub 2013 Aug 7.
Results Reference
result
Learn more about this trial
Phase I Study of Dalotuzumab (MK-0646) in Combination With Cetuximab and Irinotecan in Participants With Colorectal Cancer (MK-0646-016)
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