Phase I Study of Dalotuzumab (MK-0646) in Combination With Cetuximab and Irinotecan in Participants With Colorectal Cancer (MK-0646-016)

NCT ID: NCT00925015

Last Updated: 2018-08-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-17
• Study Completion Date: 2010-12-06

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetux/Irin - Dmab 10 mg/kg

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.

Group Type: EXPERIMENTAL

Dalotuzumab 10 mg/kg

Intervention Type: BIOLOGICAL

Dalotuzumab at 10 mg/kg was intravenously administered once weekly

Cetuximab

Intervention Type: BIOLOGICAL

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

Irinotecan

Intervention Type: DRUG

Irinotecan was administered with an intravenous infusion of 150 mg/m\^2, once every other week for 42 days

Cetux/Irin - Dmab 15/7.5 mg/kg

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.

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: BIOLOGICAL

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

Irinotecan

Intervention Type: DRUG

Irinotecan was administered with an intravenous infusion of 150 mg/m\^2, once every other week for 42 days

Dalotuzumab 15/7.5 mg/kg

Intervention Type: BIOLOGICAL

Dalotuzumab was intravenously administered, with the first infusion of 15 mg/kg, followed by subsequent infusions of 7.5 mg/kg

Dmab 10 mg/kg - Cetux/Irin (DDI)

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.

Group Type: EXPERIMENTAL

Dalotuzumab 10 mg/kg

Intervention Type: BIOLOGICAL

Dalotuzumab at 10 mg/kg was intravenously administered once weekly

Cetuximab

Intervention Type: BIOLOGICAL

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

Irinotecan

Intervention Type: DRUG

Irinotecan was administered with an intravenous infusion of 150 mg/m\^2, once every other week for 42 days

Interventions

Dalotuzumab 10 mg/kg

Dalotuzumab at 10 mg/kg was intravenously administered once weekly

Intervention Type: BIOLOGICAL

Cetuximab

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: BIOLOGICAL

Irinotecan

Irinotecan was administered with an intravenous infusion of 150 mg/m\^2, once every other week for 42 days

Intervention Type: DRUG

Dalotuzumab 15/7.5 mg/kg

Dalotuzumab was intravenously administered, with the first infusion of 15 mg/kg, followed by subsequent infusions of 7.5 mg/kg

Intervention Type: BIOLOGICAL

Other Intervention Names

MK-0646; MK-0646

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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.

Reference Type: RESULT

PMID: 23921573 (View on PubMed)

Other Identifiers

2009_602

Identifier Type: -

Identifier Source: secondary_id

0646-016

Identifier Type: -

Identifier Source: org_study_id