Safety Study of IPI-504 in Patients With Gastrointestinal Stromal Tumors (GIST) or Soft Tissue Sarcomas (STS)

NCT ID: NCT00276302

Last Updated: 2011-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2010-11-30

Brief 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

Detailed Description

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.

Conditions

Gastrointestinal Stromal Tumors; Soft Tissue Sarcomas

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Schedule A: Doses occur on Days 1, 4, 8, and 11 followed by 10 days with no study drug administration.

Group Type: EXPERIMENTAL

IPI-504

Intervention Type: DRUG

IV administration of IPI-504 for 21-day cycles. Two different schedules of treatment will be tested. On Schedule A, doses occur on Days 1, 4, 8, and 11 followed by 10 days with no study drug administration. On Schedule B, doses occur on Days 1, 4, 8, 11, 15, and 18, or twice weekly for 3 weeks continuously.

For both Schedule A and B doses will be administered ≥ 72 hours apart.

2

Schedule B: Doses occur on Days 1, 4, 8, 11, 15, and 18 (twice weekly for 3 weeks continuously).

Group Type: EXPERIMENTAL

IPI-504

Intervention Type: DRUG

IV administration of IPI-504 for 21-day cycles. Two different schedules of treatment will be tested. On Schedule A, doses occur on Days 1, 4, 8, and 11 followed by 10 days with no study drug administration. On Schedule B, doses occur on Days 1, 4, 8, 11, 15, and 18, or twice weekly for 3 weeks continuously.

For both Schedule A and B doses will be administered ≥ 72 hours apart.

Interventions

IPI-504

IV administration of IPI-504 for 21-day cycles. Two different schedules of treatment will be tested. On Schedule A, doses occur on Days 1, 4, 8, and 11 followed by 10 days with no study drug administration. On Schedule B, doses occur on Days 1, 4, 8, 11, 15, and 18, or twice weekly for 3 weeks continuously.

For both Schedule A and B doses will be administered ≥ 72 hours apart.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Infinity Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Infinity Pharmaceuticals

Principal Investigators

George D Demetri, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

Premiere Oncology

Scottsdale, Arizona, United States

Premiere Oncology

Santa Monica, California, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan Hosptials

Ann Arbor, Michigan, United States

Mount Sinai Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

Related Links

http://www.gistsupport.org/

Gist Support International

http://www.liferaftgroup.org/

Life Raft Group

Other Identifiers

IPI-504-02

Identifier Type: -

Identifier Source: org_study_id