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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Prostate Cancer, Prostatic Neoplasms, Cancer of the Prostate

Intervention / Treatment
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* Drug: IPI-504


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IPI-504: Group A<br>No Prior treatment for prostate cancer with cytotoxic chemotherapy (adjuvant or neoadjuvant chemotherapy is acceptable if completed >2 years prior to study) | Drug: IPI-504<br>* IPI-504 at 400mg/m2, IV, 2 times a week for 2 weeks with 10 days off treatment. Twenty-one (21) day cycle<br>|
| Experimental: IPI-504: Group B<br>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 | Drug: IPI-504<br>* IPI-504 at 400mg/m2, IV, 2 times a week for 2 weeks with 10 days off treatment. Twenty-one (21) day cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlate prior treatment status with clinical response as determined by PSA and radiologic response rate |  | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and tolerability of IPI-504 in patients with hormone resistant prostate cancer |  | 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hormone resistant prostate cancer, castrate resistant prostate cancer, HRPC, CRPC