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)
18 Years
N/A
Both
Gastrointestinal Stromal Tumors, Soft Tissue Sarcomas
Trial Information
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)
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
To determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies
Outcome Time Frame:
18 months
Safety Issue:
Yes
Principal Investigator
George D Demetri, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Dana-Farber Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
IPI-504-02
NCT ID:
NCT00276302
Start Date:
December 2005
Completion Date:
November 2010
Related Keywords:
- Gastrointestinal Stromal Tumors
- Soft Tissue Sarcomas
- Gastrointestinal Stromal Tumors
- Sarcoma
Name | Location |
|---|---|
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| Premiere Oncology | Santa Monica, California 90404 |
| Premiere Oncology | Scottsdale, Arizona 85260 |
| University of Michigan Hosptials | Ann Arbor, Michigan 48109 |
