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
18 Years
N/A
Male
Prostate Cancer, Prostatic Neoplasms, Cancer of the Prostate
Trial Information
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
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.
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Correlate prior treatment status with clinical response as determined by PSA and radiologic response rate
Outcome Time Frame:
12 Weeks
Safety Issue:
No
Principal Investigator
William Oh, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Dana-Farber Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
IPI-504-04
NCT ID:
NCT00564928
Start Date:
November 2007
Completion Date:
July 2010
Related Keywords:
- Prostate Cancer
- Prostatic Neoplasms
- Cancer of the Prostate
- Hormone resistant prostate cancer
- castrate resistant prostate cancer
- HRPC
- CRPC
- Neoplasms
- Prostatic Neoplasms
Name | Location |
|---|---|
| Stanford University Medical Center | Stanford, California 94305-5408 |
| Beth Israel Deaconess Medical Center | Boston, Massachusetts 02215 |
| Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| Massachusetts General Hospital | Boston, Massachusetts 02114-2617 |
| Wayne State University | Detroit, Michigan 48202 |
| San Bernardino Urological Associates | San Bernardino, California |
| University of Chicago Hospitals | Chicago, Illinois 60637 |
| University of Colorado at Denver | Denver, Colorado 80045 |
| MCG Cancer Center | Augusta, Georgia 30912 |
| Parkland Hospital | Dallas, Texas 75390 |
