Clinical trial NCT00276302: Safety Study of IPI-504 in Patients With Gastrointestinal Stromal Tumors (GIST) or Soft Tissue Sarcomas (STS)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gastrointestinal Stromal Tumors
Soft Tissue Sarcomas
Lead sponsor: Infinity Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2006-01-13
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: To determine the safety and maximum tolerated dose (MTD) of IPI-504 in GIST and STS patients who have failed prior therapies
timeFrame: 18 months
measure: To recommend a dose for subsequent studies of IPI-504
timeFrame: 18 months
Secondary outcomes:
measure: To examine the pharmacokinetic (PK) parameters of IPI-504 in GIST and STS patients
timeFrame: 18 months
measure: To assess in a preliminary way the potential anti-tumor activity of IPI-504 in GIST and STS.
timeFrame: 18 months
measure: To explore potential pharmacodynamic (PD) markers of biologic activity of IPI-504 in GIST and STS.
timeFrame: 18 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Premiere Oncology
state: Arizona
city: Santa Monica
country: United States
facility: Premiere Oncology
state: California
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Hosptials
state: Michigan
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: Dana-Farber Cancer Institute
name: George D Demetri, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: