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

Gastrointestinal Stromal Tumors Clinical Trial

Official title:

A Phase 1, Safety Assessment and Pharmacokinetic Study of IPI-504 in Patients With Either Metastatic and/or Unresectable Gastrointestinal Stromal Tumors (GIST) or Advanced or Metastatic Soft Tissue Sarcomas (STS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00276302
• Other study ID #: IPI-504-02
• Status: Completed
• Phase: Phase 1
• First received: January 11, 2006
• Last updated: January 5, 2011
• Start date: December 2005
• Est. completion date: November 2010

Study information

• Verified date: January 2011
• Source: Infinity Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors
• Sarcoma
• Soft Tissue Sarcomas

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Canada	Mount Sinai Hospital	Toronto	Ontario
United States	University of Michigan Hosptials	Ann Arbor	Michigan
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Premiere Oncology	Santa Monica	California
United States	Premiere Oncology	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Infinity Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies		18 months	Yes
Primary	To recommend a dose for subsequent studies of IPI-504		18 months	Yes
Secondary	To examine the pharmacokinetic (PK) parameters of IPI-504 in GIST and STS patients		18 months	No
Secondary	To assess in a preliminary way the potential anti-tumor activity of IPI-504 in GIST and STS.		18 months	No
Secondary	To explore potential pharmacodynamic (PD) markers of biologic activity of IPI-504 in GIST and STS.		18 months	No

External Links

•   Gist Support International
•   Life Raft Group