Clinical trial NCT00564928: A Phase 2 Study to Investigate the Clinical Activity of IPI-504 in Patients With Hormone-resistant Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Prostate Cancer
Prostatic Neoplasms
Cancer of the Prostate
Keywords: Hormone resistant prostate cancer
castrate resistant prostate cancer
HRPC
CRPC
Lead sponsor: Infinity Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2007-11-29
Enrollment: 19
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Correlate prior treatment status with clinical response as determined by PSA and radiologic response rate
timeFrame: 12 Weeks
Secondary outcomes:
measure: Assess the safety and tolerability of IPI-504 in patients with hormone resistant prostate cancer
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: San Bernardino
country: United States
facility: San Bernardino Urological Associates
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: University of Colorado at Denver
state: Colorado
city: Augusta
country: United States
facility: MCG Cancer Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Hospitals
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Dallas
country: United States
facility: Parkland Hospital
state: Texas
Study officials:
affiliation: Dana-Farber Cancer Institute
name: William Oh, MD
role: PRINCIPAL_INVESTIGATOR
References: