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

NCT00925015 | Completed Phase 1 Results

• 2 other identifiers: 0646-0162009_602
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Four weeks of Cycle 1 treatment (up to 28 days)

• 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.

  Approximately 4 weeks after last drug treatment (up to Day 293)

Secondary Outcomes (22)

• Number of Participants With Human Anti-Human Antibody (HAHA)

  Up to 12 weeks after the last administration of dalotuzumab (up to 349 days)

• Time to Maximum Concentration (Tmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone in or in Combination With Cetuximab / Irinotecan

  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

• Concentration at the End of Infusion (Ceoi) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan

  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

• Maximum Concentration (Cmax) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan

  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

• Apparent Terminal Half-life (T1/2) of Dalotuzumab Following Administration of 10 mg/kg Dalotuzumab Alone or in Combination With Cetuximab / Irinotecan

  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

Study Arms (3)

Cetux/Irin - Dmab 10 mg/kg

EXPERIMENTAL

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.

Biological: Dalotuzumab 10 mg/kg; Biological: Cetuximab; Drug: Irinotecan

Cetux/Irin - Dmab 15/7.5 mg/kg

EXPERIMENTAL

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.

Biological: Cetuximab; Drug: Irinotecan; Biological: Dalotuzumab 15/7.5 mg/kg

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

EXPERIMENTAL

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.

Biological: Dalotuzumab 10 mg/kg; Biological: Cetuximab; Drug: Irinotecan

Interventions

Dalotuzumab 10 mg/kg BIOLOGICAL

Dalotuzumab at 10 mg/kg was intravenously administered once weekly

Also known as: MK-0646

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

Cetuximab 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

Cetux/Irin - Dmab 10 mg/kg; Cetux/Irin - Dmab 15/7.5 mg/kg; Dmab 10 mg/kg - Cetux/Irin (DDI)

Irinotecan DRUG

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

Cetux/Irin - Dmab 10 mg/kg; Cetux/Irin - Dmab 15/7.5 mg/kg; Dmab 10 mg/kg - Cetux/Irin (DDI)

Dalotuzumab 15/7.5 mg/kg BIOLOGICAL

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

Also known as: MK-0646

Cetux/Irin - Dmab 15/7.5 mg/kg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 23921573 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

dalotuzumab; Cetuximab; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: June 19, 2009
• Study Start: June 17, 2009
• Primary Completion: July 28, 2010
• Study Completion: December 6, 2010
• Last Updated: August 15, 2018
• Results First Posted: August 2, 2017

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share