Clinical trial NCT00551213: A Study to Determine the Activity of Robatumumab (SCH 717454, MK-7454) in Participants With Relapsed or Recurrent Colorectal Cancer (P04721, MK-7454-003)
Official title: A Fixed-Sequence, Open-Label Study to Determine the Activity of SCH 717454 as Assessed by Positron Emission Tomography in Subjects With Relapsed or Recurrent Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: anti-IGF-1R
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-10-30
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: After the first robatumumab dose in Period 2 (Up to approximately 4 weeks after first robatumumab dose in Period 1)
Secondary outcomes:
measure: Number of Participants Who Experienced One or More Adverse Events (AEs)
timeFrame: Up to 30 days after last dose of study drug (Up to approximately 22 weeks)
measure: Best Overall Tumor Response Per Investigator Review
timeFrame: Up to 30 days after last dose of study drug (Up to approximately 22 weeks)
measure: Number of Participants Who Discontinued Study Drug Due to an AE
timeFrame: Up to last dose of study drug (Up to approximately 18 weeks)
measure: Best Overall Tumor Response Per Central Review
timeFrame: Up to 30 days after last dose of study drug (Up to approximately 22 weeks)
measure: Change From Baseline in Tumor Growth Rate
timeFrame: Baseline and up to approximately 22 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.