Open AccessA 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
Author(s) -
Lin Edward H.,
Lenz HeinzJosef,
Saleh Mansoor N.,
Mackenzie Mary J.,
Knost James A.,
Pathiraja Kumudu,
Langdon Ronald B.,
Yao SiuLong,
Lu Brian D.
Publication year - 2014
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.263
Subject(s) - clinical endpoint , medicine , pharmacodynamics , colorectal cancer , response evaluation criteria in solid tumors , standardized uptake value , chemotherapy , cancer , insulin like growth factor , progressive disease , gastroenterology , phases of clinical research , oncology , randomized controlled trial , urology , nuclear medicine , pharmacokinetics , positron emission tomography , receptor , growth factor
Abstract Overexpression of insulin‐like growth factor receptor type 1 ( IGF ‐1R) may promote tumor development and progression in some cancer patients. Our objective was to assess tumor uptake of fluorodeoxyglucose by positron‐emission tomography in patients with chemotherapy‐refractory colorectal cancer treated with an anti‐insulin‐like growth factor receptor type 1 (anti‐ IGF ‐1R) monoclonal antibody, robatumumab. This was a randomized, open‐label study with two periods (P1 and P2). Patients were randomized 3:1 into treatment arms R/R and C/R that received, respectively, one cycle of 0.3 mg/kg robatumumab or one or more cycles of second‐line chemotherapy in P1, followed in either case by 10 mg/kg robatumumab biweekly in P2. The primary measure of fluorodeoxyglucose uptake was maximum standardized uptake value ( SUV max ). The primary endpoint was the proportion of patients in the R/R arm having a mean percent decrease from baseline in SUV max (Di SUV ) greater than 20% 12–14 days postdose in P2. Secondary endpoints included Response Evaluation Criteria in Solid Tumors ( RECIST )‐defined tumor response and pharmacodynamic measures of target engagement. Among 41 patients who were evaluable for the primary endpoint, seven (17%, 95% CI 7%–32%) had Di SUV greater than 20%. Fifty robatumumab‐treated patients were evaluable for RECIST ‐defined tumor response and six (12%) had stable disease lasting greater than or equal to 7 weeks in P2. Pharmacodynamic endpoints indicated target engagement after dosing with 10 mg/kg robatumumab, but not 0.3 mg/kg. The most frequently reported adverse events were fatigue/asthenia, nausea, anorexia, and gastrointestinal disturbances. In this study, few patients with chemotherapy‐refractory colorectal cancer appeared to benefit from treatment with the IGF ‐1R antagonist robatumumab.