Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed 18 and over Pharmaceutical / Industry IPI-504-02 NCT00276302

Trial Description

Summary

The primary objectives of the study are:

• Determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies

• Recommend a dose for subsequent studies of IPI-504

Further Study Information

IPI-504 is a novel, water-soluble analog of 17-AAG and a potent inhibitor of Hsp90. Hsp90's role in the cell is to control the proper folding, function, and viability of various "client" proteins. Many of these client proteins (such as AKT, Her-2, Bcr-Abl, PDGFR-α, and c-Kit) are oncoproteins or important cell signaling proteins. In patients with GIST, mutations in the tyrosine kinase receptor Kit play a critical role in the pathogenesis of this disease. Inhibition of Kit signaling with the tyrosine kinase inhibitor Imatinib (IM) is a very effective treatment for GIST patients. However, new mutations arise in Kit conferring resistance to IM treatment which results in disease progression. Kit is a client protein of Hsp90 and is sensitive to IPI-504. In Soft Tissue Sarcomas, there may be genetic abnormalities that lead to the expression of certain proteins that drive the growth of cancer. These cancer-driving proteins may be stimulated by HSP90. This provides a scientific rationale for Phase 1 clinical testing of IPI-504 in patients with advanced GIST and STS who have failed prior therapies.

Eligibility Criteria

Inclusion Criteria:

• Pathologically confirmed diagnosis of GIST or STS

• Failed prior therapies

• ECOG performance status of 0-2

• Ability to adhere to the study visit schedule and all protocol requirements

Exclusion Criteria:

• Previous treatment with 17-AAG, DMAG, or other known Hsp90 inhibitor

• Participation in any investigational drug study or treatment with any other kinase inhibitor therapy within 2 weeks preceding start of treatment

• Concurrent radiation therapy is not permitted

• Concurrent treatment with any agent that alters CYP3A activity

• Concurrent treatment with any agent that may prolong the QTc interval

• Myocardial infarction or active ischemic heart disease within 6 months

• History of arrhythmia

• Baseline QTc >450

• Grade 3 or greater peripheral neuropathy

• Renal insufficiency, serum creatinine >1.5 x ULN

• Platelets < 100,000 mm3

• AST and / or ALT > 2.5 x ULN

• ANC <1,500 cells/mm3

• Alkaline phosphatase > 2.5 x ULN

• Amylase and lipase > 1.5 x ULN

• Hemoglobin < 9.0 g/dL

Trial Contact Information

Trial Lead Organizations/Sponsors

Infinity Pharmaceuticals

George D Demetri, MD, PhD

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00276302
Information obtained from ClinicalTrials.gov on July 16, 2008