A Phase 2 Study to Investigate the Clinical Activity of IPI-504 in Patients With Hormone-resistant Prostate Cancer

Phase 2

Completed

• Conditions: Prostate Cancer; Prostatic Neoplasms; Cancer of the Prostate
• Interventions: Drug: IPI-504

• Registration Number: NCT00564928
• Lead Sponsor: Infinity Pharmaceuticals, Inc.

Brief Summary

To determine:

* Anti-tumor activity of IPI-504 in 2 groups of subjects with hormone resistant prostate cancer.

* Group A - subjects who have not previously received chemotherapy

* Group B - sujects who have received prior chemotherapy or could not tolerate chemotherapy.

* Clinical response will be determined by PSA and radiological response

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. Inhibition of HSP-90 leads to the proteasomal degradation of these proteins.

In patients with HRPC,there are several proteins that are important in the progression of HRPC, including AR, AKT and Her-2. All of these are client proteins of Hsp90 and in response to Hsp90 inhibition are degraded by their proteasome. Preclinical studies have shown that Hsp90 inhibition causes a dose dependent degradation of these client proteins and growth inhibition of prostate cancer in xenograft tumors.

Study Timeline

• Study Start: 2007-11
• Study First Submitted: 2007-11-27
• Study First Submitted QC: 2007-11-28
• Study First Posted: 2007-11-29
• Primary Completion: 2010-03
• Study Completion: 2010-07
• Status Verified: 2012-12
• Disposition First Submitted: 2012-12-06
• Disposition First Submitted QC: 2012-12-06
• Last Update Submitted: 2012-12-07
• Disposition First Posted: 2012-12-10
• Last Update Posted: 2012-12-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 19

Inclusion Criteria

• Adenocarcinoma of the prostate

• Resolution of acute toxic side effects of prior chemotherapy

• Castration resistant disease despite ongoing chemical or surgical castration

• ECOG 0-1

• PSA greater than or equal to 2

• Group A -

  • No Prior treatment for prostate cancer with cytotoxic chemotherapy (neoadjuvant, adjuvant treatment permitted if more than 2 years out)

• Group B

  • Radiographic evidence of metastatic disease
  • Prior tx with docetaxel-minimum of 2 cycles with progression by RECIST or PSA or intolerant of tx
  • Maximum of 3 prior chemotherapies

Exclusion Criteria

• Small cell carcinoma of the prostate
• Treatment within 2 weeks with approved, investigational, or small molecule
• Treatment within 4 weeks with biologic or external beam radiation
• ANC <1,500 cells m3; Platelets <100,000 mm3; Hemoglobin <9.0g/dL
• AST/ALT >2.5 ULN
• Serum creatinine >3.0mg/dL
• Active keratitis or keratoconjunctivitis
• Previous treatment with 17-AAG, DMAG; or any other HSP-90 inhibitor
• Baseline Qtc >450 mses

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IPI-504: Group A	IPI-504	No Prior treatment for prostate cancer with cytotoxic chemotherapy (adjuvant or neoadjuvant chemotherapy is acceptable if completed \>2 years prior to study)
IPI-504: Group B	IPI-504	* Must have evidence of radiographic metastatic disease * Must have been treated with a docetaxel-based chemotherapy regimen for HRPC with a minimum of 2 cycles with either PSA or RECIST defined radiographic progression during or witin 60 days of completeing docetaxel based chemotheraph or be intolerant of docetaxel-based chemotherapy * No more than three prior chemotherapies regimens for HRPC

Primary Outcome Measures

Name	Time	Method
Correlate prior treatment status with clinical response as determined by PSA and radiologic response rate	12 Weeks

Secondary Outcome Measures

Name	Time	Method
Assess the safety and tolerability of IPI-504 in patients with hormone resistant prostate cancer	12 Weeks

Trial Locations

Locations (10)

University of Colorado at Denver; 🇺🇸 Denver, Colorado, United States

Wayne State University; 🇺🇸 Detroit, Michigan, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Parkland Hospital; 🇺🇸 Dallas, Texas, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

MCG Cancer Center; 🇺🇸 Augusta, Georgia, United States

San Bernardino Urological Associates; 🇺🇸 San Bernardino, California, United States

Stanford University Medical Center; 🇺🇸 Stanford, California, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Chicago Hospitals; 🇺🇸 Chicago, Illinois, United States