Cancer of the Prostate, Prostate Cancer, Prostatic Neoplasms
Conditions
Keywords
Hormone resistant prostate cancer, castrate resistant prostate cancer, HRPC, CRPC
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.
Interventions
DRUGIPI-504
IPI-504 at 400mg/m2, IV, 2 times a week for 2 weeks with 10 days off treatment. Twenty-one (21) day cycle
Sponsors
Infinity Pharmaceuticals, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Correlate prior treatment status with clinical response as determined by PSA and radiologic response rate | 12 Weeks |
Secondary
| Measure | Time frame |
|---|---|
| Assess the safety and tolerability of IPI-504 in patients with hormone resistant prostate cancer | 12 Weeks |
Countries
United States
Outcome results
None listed