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

Prostate Cancer Clinical Trial

— IPI-504-04  

Official title:

A Phase 2 Open-Label Study to Investigate the Pharmacodynamics and Clinical Activity of IPI-504 in Patients With Castration-Resistant Prostate Cancer Stratified by Prior Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00564928
• Other study ID #: IPI-504-04
• Status: Completed
• Phase: Phase 2
• First received: November 27, 2007
• Last updated: December 7, 2012
• Start date: November 2007
• Est. completion date: July 2010

Study information

• Verified date: December 2012
• Source: Infinity Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: July 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cancer of the Prostate
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• IPI-504
IPI-504 at 400mg/m2, IV, 2 times a week for 2 weeks with 10 days off treatment. Twenty-one (21) day cycle

Locations

Country	Name	City	State
United States	MCG Cancer Center	Augusta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Chicago Hospitals	Chicago	Illinois
United States	Parkland Hospital	Dallas	Texas
United States	University of Colorado at Denver	Denver	Colorado
United States	Wayne State University	Detroit	Michigan
United States	San Bernardino Urological Associates	San Bernardino	California
United States	Stanford University Medical Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Infinity Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlate prior treatment status with clinical response as determined by PSA and radiologic response rate		12 Weeks	No
Secondary	Assess the safety and tolerability of IPI-504 in patients with hormone resistant prostate cancer		12 Weeks	Yes