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

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 I

MedlinePlus related topics:

Cancer Soft Tissue Sarcoma

ChemIDplus related topics:

IPI-504 17-(Allylamino)-17-demethoxygeldanamycin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Safety Study

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)

Further study details as provided by Infinity Pharmaceuticals:

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 ]

Estimated Enrollment:	92
Study Start Date:	December 2005
Estimated Study Completion Date:	August 2008
Estimated Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental 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.
2: Experimental 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

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

Investigators


Principal Investigator:	George D Demetri, MD, PhD	Dana-Farber Cancer Institute

More Information

Gist Support International This link exits the ClinicalTrials.gov site

Life Raft Group This link exits the ClinicalTrials.gov site

Responsible Party:	Infinity Pharmaceuticals ( Krista McKee, MEd, MPH )
Study ID Numbers:	IPI-504-02
First Received:	January 11, 2006
Last Updated:	April 18, 2008
ClinicalTrials.gov Identifier:	NCT00276302
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Neoplasms, Connective and Soft Tissue

Digestive System Diseases

Digestive System Neoplasms

Gastrointestinal Diseases

Malignant mesenchymal tumor

Sarcoma

Gastrointestinal Neoplasms

Gastrointestinal Stromal Tumors

Soft tissue sarcomas

Additional relevant MeSH terms:

Neoplasms

Neoplasms by Histologic Type

Neoplasms by Site

ClinicalTrials.gov processed this record on September 05, 2008

Sponsored by:	Infinity Pharmaceuticals
Information provided by:	Infinity Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00276302