A Study to Determine the Activity of Robatumumab (SCH 717454, MK-7454) in Participants With Relapsed or Recurrent Colorectal Cancer (P04721, MK-7454-003)

NCT00551213 | Completed Phase 2 Results

• 2 other identifiers: P04721MK-7454-003
• Study Type: interventional
• Target: 67
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study was to determine the activity of two doses of robatumumab (SCH 717454, MK-7454) in participants with relapsed or recurrent colorectal cancer. The primary study hypothesis was that decreases in Positron Emission Tomography (PET)-assessed tumor glucose metabolism (i.e., fluorodeoxyglucose \[FDG\] standardized uptake value \[SUV\]) following administration of 10 mg/kg robatumumab will exceed those following administration of 0.3 mg/kg robatumumab in participants with relapsed or recurrent colorectal cancer who had progressed after first-line chemotherapy. Investigator choices of standard chemotherapy: irinotecan as a single agent +/- cetuximab OR capecitabine as a single agent, OR FOLFOX (leucovorin calcium \[folinic acid\]\[FOL\] + fluorouracil \[F\] + oxaliplatin \[OX\]) OR CAPEO(capecitabine \[CAPE\] or Xeloda® \[XEL\] + oxaliplatin \[OX\]) OR FOLFIRI (leucovorin calcium \[folinic acid\]\[FOL\] + fluorouracil \[F\] + irinotecan \[IRI\]) +/- cetuximab OR cetuximab as a single agent.

Conditions

Colorectal Cancer

Keywords

anti-IGF-1R

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a >20% Decrease in Positron Emission Tomography (PET)-Assessed Tumor Glucose Metabolism: Fluorodeoxyglucose (FDG) Standardized Uptake Value (SUV) in the Target Lesion

  FDG-PET was used in this study to detect the biological activity of modulation of the target within the tumor. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 was used to select the target lesion. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs were identified as target lesions and recorded and measured at Baseline. The changes in SUVmax were calculated using the formula: (endpoint SUVmax - baseline SUVmax)/baseline SUVmax as a percentage. If multiple lesions had been measured at a visit, percentages calculated for all target lesions were averaged to find the decrease during the treatment period per participant. FDG SUVmax responder was defined as participants with \>20% decrease in SUVmax after the first cycle of robatumumab in Period 2.

  After the first robatumumab dose in Period 2 (Up to approximately 4 weeks after first robatumumab dose in Period 1)

Secondary Outcomes (5)

• Number of Participants Who Experienced One or More Adverse Events (AEs)

  Up to 30 days after last dose of study drug (Up to approximately 22 weeks)

• Best Overall Tumor Response Per Investigator Review

  Up to 30 days after last dose of study drug (Up to approximately 22 weeks)

• Number of Participants Who Discontinued Study Drug Due to an AE

  Up to last dose of study drug (Up to approximately 18 weeks)

• Best Overall Tumor Response Per Central Review

  Up to 30 days after last dose of study drug (Up to approximately 22 weeks)

• Change From Baseline in Tumor Growth Rate

  Baseline and up to approximately 22 weeks

Study Arms (2)

Robatumumab→Robatumumab

EXPERIMENTAL

Participants receive 1 dose of robatumumab 0.3 mg/kg intravenously (IV) followed by 1 dose of robatumumab 10 mg/kg IV once every 2 weeks (Q2W) until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.

Biological: Robatumumab

Chemotherapy→Robatumumab

ACTIVE COMPARATOR

Participants receive 1 cycle of standard colorectal cancer chemotherapy currently approved and available on the market for use in colorectal cancer (to be selected by the Investigator based on participant's prior treatment) followed by 1 dose of robatumumab 10 mg/kg IV Q2W until disease progression. A cycle of robatumumab is defined as 2 weeks of treatment (i.e., 1 dose of robatumumab) with no recovery period between cycles.

Biological: Robatumumab; Drug: Irinotecan; Biological: Cetuximab; Drug: Capecitabine; Drug: FOLFOX; Drug: CAPEOX/XELOX; Drug: FOLFIRI

Interventions

Robatumumab BIOLOGICAL

Chemotherapy→Robatumumab; Robatumumab→Robatumumab

Irinotecan DRUG

Chemotherapy→Robatumumab

Cetuximab BIOLOGICAL

Chemotherapy→Robatumumab

Capecitabine DRUG

Chemotherapy→Robatumumab

FOLFOX DRUG

Leucovorin calcium (folinic acid)(FOL) + 5-fluorouracil (F)+ oxaliplatin (OX)

Chemotherapy→Robatumumab

CAPEOX/XELOX DRUG

Capecitabine (CAPE) or Xeloda® (XEL) + oxaliplatin (OX)

Chemotherapy→Robatumumab

FOLFIRI DRUG

Leucovorin calcium (folinic acid)(FOL) + 5-fluorouracil (F)+ irinotecan (IRI)

Chemotherapy→Robatumumab

Eligibility Criteria

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

You may qualify if:

• Older than 18 years of age, of any race, and gender;
• Diagnosis of histologically confirmed relapsed or recurrent colorectal carcinoma that has progressed on at least first-line therapy;
• Must have a computed tomography (CT) or magnetic resonance imaging (MRI) scan performed at some point during their immediate prior treatment or observation in order to determine tumor growth rate;
• Must have measurable disease on a CT or MRI study, performed during Screening;
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status of \<=2 and a minimum life expectancy of ≥4 months;
• Must have adequate organ function within 3 weeks prior to treatment assignment

You may not qualify if:

• History of another malignancy;
• Known treated or untreated leptomeningeal metastasis, or a metastatic central nervous system lesion;
• Surgery within 3 weeks;
• Radiation therapy within 6 weeks;
• A history of uncontrolled diabetes mellitus, defined as a hemoglobin A1C of \>7.5% in a participant with known diabetes mellitus;
• A recent myocardial infarction (within the past year); or a participant who at the time of Screening presents with unstable or uncontrolled angina, New York Heart Association Class III or IV congestive heart failure, uncontrolled hypertension, clinically significant cardiac dysrhythmia or clinically significant electrocardiogram abnormality;
• An active infection;
• Has clinically significant hepatitis at Screening, or is hepatitis C antibody positive, hepatitis B surface antigen positive, or human immunodeficiency virus (HIV) seropositive.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Lin EH, Lenz HJ, Saleh MN, Mackenzie MJ, Knost JA, Pathiraja K, Langdon RB, Yao SL, Lu BD. A randomized, phase II study of the anti-insulin-like growth factor receptor type 1 (IGF-1R) monoclonal antibody robatumumab (SCH 717454) in patients with advanced colorectal cancer. Cancer Med. 2014 Aug;3(4):988-97. doi: 10.1002/cam4.263. Epub 2014 Jun 6.

  PMID: 24905030 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

robatumumab; Irinotecan; Cetuximab; Capecitabine; Folfox protocol; XELOX; IFL protocol

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)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2007
• First Posted: October 30, 2007
• Study Start: November 21, 2007
• Primary Completion: June 4, 2009
• Study Completion: June 4, 2009
• Last Updated: August 24, 2018
• Results First Posted: December 15, 2015

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will share