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

This study has been completed.
Sponsor:
Information provided by:
Infinity Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00276302
First received: January 11, 2006
Last updated: January 5, 2011
Last verified: January 2011
  Purpose

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

Condition Intervention Phase
Gastrointestinal Stromal Tumors
Soft Tissue Sarcomas
Drug: IPI-504
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Infinity Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • To determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
  • To recommend a dose for subsequent studies of IPI-504 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To examine the pharmacokinetic (PK) parameters of IPI-504 in GIST and STS patients [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To assess in a preliminary way the potential anti-tumor activity of IPI-504 in GIST and STS. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • To explore potential pharmacodynamic (PD) markers of biologic activity of IPI-504 in GIST and STS. [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: December 2005
Study Completion Date: November 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00276302

Locations
United States, Arizona
Premiere Oncology
Scottsdale, Arizona, United States, 85260
United States, California
Premiere Oncology
Santa Monica, California, United States, 90404
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Hosptials
Ann Arbor, Michigan, United States, 48109
Canada, Ontario
Mount Sinai Hospital
Toronto, Ontario, Canada, M5G 1X5
Sponsors and Collaborators
Infinity Pharmaceuticals, Inc.
Investigators
Principal Investigator: George D Demetri, MD, PhD Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Krista McKee, MEd, MPH, Infinity Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00276302     History of Changes
Other Study ID Numbers: IPI-504-02
Study First Received: January 11, 2006
Last Updated: January 5, 2011
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Sarcoma
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue

ClinicalTrials.gov processed this record on October 29, 2014