Pharmacokinetically guided phase 1 trial of the IGF-1 receptor antagonist RG1507 in children with recurrent or refractory solid tumors Journal Article


Authors: Bagatell, R.; Herzog, C. E.; Trippett, T. M.; Grippo, J. F.; Cirrincione-Dall, G.; Fox, E.; Macy, M.; Bish, J.; Whitcomb, P.; Aikin, A.; Wright, G.; Yurasov, S.; Balis, F. M.; Gore, L.
Article Title: Pharmacokinetically guided phase 1 trial of the IGF-1 receptor antagonist RG1507 in children with recurrent or refractory solid tumors
Abstract: Purpose: This pediatric phase I study was designed to identify the doses of RG1507, a monoclonal antibody against the Type 1 Insulin-like Growth Factor Receptor (IGF1R), that achieves exposures equivalent to those achieved in adults at recommended doses. Experimental Design: Children with relapsed or refractory solid tumors were treated using the same doses and administration schedules of RG1507 (3 and 9 mg/kg/wk, and 16 mg/kg every 3 weeks [q3W]) as those studied in adults. Detailed pharmacokinetic (PK) sampling was performed after the first dose; selected peak and trough levels were subsequently obtained. Target exposures were ≥85% of mean areas under concentration x time curves (AUCs) in adults at doses of 9 mg/kg/wk and 16 mg/kg q3W. A maximum tolerated dose could be identified if dose-limiting toxicities (DLT) occurred. Results: Thirty-one evaluable patients aged 3-17 years were enrolled at 3 mg/kg/wk (n=3), 9 mg/kg/wk (n = 18), or 16 mg/kg q3W (n = 10). There were no DLTs. At 9 mg/kg/wk the mean AUC0-7d (21,000 μg h/ mL) exceeded the target (16,000 mg h/mL). At 16 mg/kg q3W, the mean AUC021d (70,000 μg h/mL) exceeded the target (59,400 mg h/mL). Clearance normalized to body weight was age dependent. There were no objective responses. Seven patients had stable disease for >12 weeks, including two patients with osteosarcoma with stable disease for 52+ and 78+ weeks. Conclusions: The recommended doses of RG1507 in children with solid tumors are 9 mg/kg/wk and 16 mg/kg q3W. This flexible design is well suited for trials of agents associated with limited toxicity. ©2010 AACR.
Journal Title: Clinical Cancer Research
Volume: 17
Issue: 3
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2011-02-01
Start Page: 611
End Page: 619
Language: English
DOI: 10.1158/1078-0432.ccr-10-1731
PROVIDER: scopus
PUBMED: 21127194
PMCID: PMC4283561
DOI/URL:
Notes: --- - "Export Date: 4 March 2011" - "CODEN: CCREF" - "Source: Scopus"
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  1. Geraldine Patrice Wright
    2 Wright