A Phase I Dose Escation Study of IPI-493

A Phase I Dose Escation Study of IPI-493

Solid Tumors

Terminated

1

Start Date 07/30/2008

Age of Trial (yrs) 15.8

Gleevec-resistant

HSP90 inhibitor

Destroy KIT

GIST not specified. GIST patient enrollment unknown.

IPI-493-01

Infinity Pharmaceuticals

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Oral

This study has been terminated.
( Drug exposure of retaspimycin HCl (IPI-504) was superior to IPI-493, Infinity will focus exclusively on retaspimycin).
This phase I trial was to establish the safety and maximum tolerated dose of IPI-493. IPI-493 is an oral HSP90 inhibitor manufactured by Infinity Pharmaceuticals.
The multi-center, Phase 1 study of oral IPI-493 is designed as a dose-escalation trial in patients with advanced solid tumors. The primary objectives of the study are to assess safety and tolerability and to identify a treatment regimen (dose and schedule) for subsequent studies of IPI-493. Anti-tumor activity of IPI-493 will be measured using computed tomography (CT) imaging using Response Evaluation Criteria in Solid Tumors, as well as disease specific markers. Pharmacokinetics parameters, biologic activity, and effects of IPI-493 on pharmacodynamic markers of biological activity will also be assessed.
Hsp90 controls the proper folding, function, and stability of various "client" proteins within cells. Many of the clients of Hsp90 (such as Akt, Bcr-Abl, EGFR, Flt-3, c-Kit and PDGFR α) are oncoproteins or important cell-signaling proteins, and therefore are critical for tumor cell growth and survival. Inhibition of Hsp90 results in degradation of these proteins, which abrogates growth and survival signaling and leads to tumor cell death.
"Despite recent advances in cancer treatment, there remains a very high level of unmet need in oncology," stated David S. Grayzel, M.D., vice president, clinical development and medical affairs. "Targeted anti-chaperone therapy via inhibition of Hsp90 represents a significant potential strategy for treating patients with cancer. An effective, oral inhibitor of Hsp90 is a highly desirable complement to the i.v. agent for patient convenience, dosing flexibility and the potential for combination with other anti-cancer agents in a number of treatment settings."