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

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Colorectal Cancer

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT00551213

MK-7454-003 (Other Identifier)

P04721

Details and patient eligibility

About

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.

Full description

Standard chemotherapy was used as a positive validation arm. Randomization was performed so that there could be no bias in the selection of participants for enrollment into the fixed-sequence arms. Once three chemotherapy-treated participants demonstrated decreases in FDG-PET SUV in the target lesion (i.e., >20% decrease in SUVmax in the defined target lesion) in the PET/computed tomography (CT) scan performed following Cycle 1 Period 1 treatment, it was concluded that this positive validation arm had accomplished its purpose, and all subsequent participants enrolled in the study were assigned treatment with robatumumab for Period 1. There was no intention to compare the data in either period across participants who received chemotherapy with those who received robatumumab.

Enrollment: 67 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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67 participants in 2 patient groups

Robatumumab→Robatumumab

Experimental group

Description:

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.

Treatment:

Biological: Robatumumab

Chemotherapy→Robatumumab

Active Comparator group

Description:

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.

Treatment:

Drug: FOLFOX

Biological: Cetuximab

Drug: Irinotecan

Biological: Robatumumab

Drug: Capecitabine

Drug: CAPEOX/XELOX

Drug: FOLFIRI