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Clin Cancer Res. 2007 Oct 1;13(19):5834-40.

Phase I dose escalation study of the anti insulin-like growth factor-I receptor monoclonal antibody CP-751,871 in patients with refractory solid tumors.

Author information

1
Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. haluska.paul@mayo.edu

Abstract

PURPOSE:

This phase I study was undertaken to define the maximum tolerated dose, safety, and pharmacokinetic profile of CP-751,871.

EXPERIMENTAL DESIGN:

Using a rapid dose escalation design, patients with advanced nonhematologic malignancies were treated with CP-751,871 in four dose escalation cohorts. CP-751,871 was administered i.v. on day 1 of each 21-day cycle. Pharmacokinetic evaluation was done in all treatment cohorts during cycles 1 and 4.

RESULTS:

Twenty-four patients received 110 cycles at four dose levels. The maximum tolerated dose exceeded the maximal feasible dose of 20 mg/kg and, thus, was not identified. Treatment-related toxicities were generally mild. The most common adverse events were hyperglycemia, anorexia, nausea, elevated aspartate aminotransferase, elevated gamma-glutamyltransferase, diarrhea, hyperuracemia, and fatigue. At 20 mg/kg, 10 of 15 patients experienced stability of disease. Two of these patients experienced long-term stability. There were no objective responses. Pharmacokinetic analysis revealed a dose-dependent increase in CP-751,871 exposure and approximately 2-fold accumulation on repeated dosing in 21-day cycles. Plasma concentrations of CP-751,871 attained were several log-fold greater than the biologically active concentration. Treatment with CP-751,871 increased serum insulin and human growth hormone levels, with modest increases in serum glucose levels.

CONCLUSIONS:

CP-751,871 has a favorable safety profile and was well tolerated when given in continuous cycles. At the maximal feasible dose of 20 mg/kg, there was a moderate accumulation in plasma exposure, and most of the treated patients experienced stability of disease.

PMID:
17908976
DOI:
10.1158/1078-0432.CCR-07-1118
[Indexed for MEDLINE]
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