Clinical trial NCT00925015: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-06-19
Enrollment: 20
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Dose-limiting Toxicities (DLTs)
timeFrame: Four weeks of Cycle 1 treatment (up to 28 days)
measure: Number of Participants With an Adverse Event (AE)
timeFrame: Approximately 4 weeks after last drug treatment (up to Day 293)
Secondary outcomes:
measure: Number of Participants With Human Anti-Human Antibody (HAHA)
timeFrame: Up to 12 weeks after the last administration of dalotuzumab (up to 349 days)
measure: Time to Maximum Concentration (Tmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone in or in Combination With Cetuximab / Irinotecan
timeFrame: 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
measure: Concentration at the End of Infusion (Ceoi) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
timeFrame: 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
measure: Maximum Concentration (Cmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
timeFrame: 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
measure: Apparent Terminal Half-life (T1/2) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
timeFrame: 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
measure: Clearance From Plasma (CL) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
timeFrame: 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
measure: Steady-state Volume of Distribution (Vss) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan
timeFrame: 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
measure: 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
timeFrame: 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
measure: 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
timeFrame: 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
measure: Tmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
measure: Cmax of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
measure: T1/2 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
measure: CL of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
measure: Vss of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
measure: AUC0-24 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8 and 24 h after initiation of cetuximab infusion
measure: AUC0-168 of Cetuximab Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 2, 5, 8, 24, 48, 96 and 168 h after initiation of cetuximab infusion
measure: Tmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
measure: Cmax of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
measure: T1/2 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
measure: CL of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
measure: Vss of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8, 24, and 48 h after completion of Irinotecan infusion
measure: AUC0-24 of Irinotecan Following Administration of Cetuximab / Irinotecan Alone, or in Combination With 10 mg/kg Dalotuzumab
timeFrame: Cycle 1: Day 15 and Day 29 at predose, 1, 5, 8 and 24 h after completion of Irinotecan infusion
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.