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

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)

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

Study Overview

• Status: Completed
• Conditions: Gastrointestinal Stromal Tumors; Soft Tissue Sarcomas
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • Premiere Oncology
  • California
    • Santa Monica, California, United States, 90404
      • Premiere Oncology
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Hosptials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Schedule A: Doses occur on Days 1, 4, 8, and 11 followed by 10 days with no study drug administration.	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.
Experimental: 2; Schedule B: Doses occur on Days 1, 4, 8, 11, 15, and 18 (twice weekly for 3 weeks continuously).	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies	18 months
To recommend a dose for subsequent studies of IPI-504	18 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To examine the pharmacokinetic (PK) parameters of IPI-504 in GIST and STS patients	18 months
To assess in a preliminary way the potential anti-tumor activity of IPI-504 in GIST and STS.	18 months
To explore potential pharmacodynamic (PD) markers of biologic activity of IPI-504 in GIST and STS.	18 months

Collaborators and Investigators

• Sponsor: Infinity Pharmaceuticals, Inc.
• Investigators: Principal Investigator: George D Demetri, MD, PhD, Dana-Farber Cancer Institute

Publications and helpful links

Helpful Links

• Gist Support International
• Life Raft Group

Study record dates

Study Major Dates

• Study Start: December 1, 2005
• Primary Completion (Actual): November 1, 2010
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: January 11, 2006
• First Submitted That Met QC Criteria: January 11, 2006
• First Posted (Estimate): January 13, 2006

Study Record Updates

• Last Update Posted (Estimate): January 6, 2011
• Last Update Submitted That Met QC Criteria: January 5, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Sarcoma; Gastrointestinal Stromal Tumors
• Other Study ID Numbers: IPI-504-02