A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate

Study Overview
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Brief Summary
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A 2-part, Phase 1-2, open-label, parallel group, randomized study in patients with Castration-Resistant Prostate Cancer (CRPC) who are no longer responding to treatment with abiraterone and steroids. In Part A (Phase 1), patients will continue to receive the same doses of abiraterone and steroids they were receiving prior to study entry and will be randomized to receive 1 of 2 different treatment regimens of AT13387 in combination with abiraterone. Once the best regimen is established in Part A, based on safety and antitumor activity, patients will be randomized to the selected treatment regimen and dose of AT13387 in combination with abiraterone or AT13387 alone in Part B (Phase 2).

Official Title
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A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate in the Treatment of Castration-Resistant Prostate Cancer (CRPC) no Longer Responding to Abiraterone

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: AT13387
* Drug: abiraterone acetate
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion: Must have prostate cancer Have received prior castration by orchiectomy and/or hormone therapy Males >18 years of age Normal activity level for self care Have been receiving abiraterone therapy with a steroid for ≥1 month Have disease progression on abiraterone as defined by either PSA progression, radiographic or bone progression Have adequate bone marrow, liver and kidney function Must be willing to provide pre-existing tumor samples, if this material exists. If pre-existing samples are not available, a sample must be obtained during screening Must be willing and able to provide written informed consent and comply with the protocol and study procedures Exclusion: Prior anti-cancer treatment with any Heat Shock Protein 90 (HSP90) inhibitor or histone deacetylase (HDAC) inhibitor compound Have received chemotherapy within 4 weeks prior to receiving study drug Prior prostate surgery or radiotherapy within 4 weeks from the first dose of study drug Hypersensitivity to AT13387 or other components of the drug product Treatment with any investigational drug within 4 weeks prior to the first dose of study drug Severe systemic diseases or active uncontrolled infections Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors Abnormal heart function Other cancer except for adequately treated basal cell or squamous cell carcinoma of the skin, or superficial bladder cancer, or other cancer from which the subject has been disease-free for at least 3 years; No known brain or CNS involvement Unable to receive corticosteroids or history of pituitary or adrenal dysfunction Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A, Regimen 1<br>AT13387 given as a 1-hr IV infusion at a starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle, in combination with abiraterone acetate 1000 mg by mouth (PO) daily (QD) and prednisone or prednisolone 5 mg PO twice daily. | Drug: AT13387<br>* Regimen 1: AT13387, given as 1-hr intravenous infusion at starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle. Regimen 2: AT13387, given as 1-hr IV infusion at starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle.<br>* Other names: onalespib;Drug: abiraterone acetate<br>* 1000 mg PO daily.<br>Drug: Prednisone<br>* 5 mg PO twice daily.<br>* Other names: prednisolone;|
| Experimental: Part A, Regimen 2<br>At13387 administered as a 1-hr IV infusion at a starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle, in combination with abiraterone acetate 1000 mg by mouth (PO) daily (QD) and prednisone or prednisolone 5 mg PO twice daily. | Drug: AT13387<br>* Regimen 1: AT13387, given as 1-hr intravenous infusion at starting dose of 220 mg/m2 once weekly for 3 weeks in a 4-week cycle. Regimen 2: AT13387, given as 1-hr IV infusion at starting dose of 120 mg/m2 on Day 1 and Day 2 weekly for 3 weeks in a 4-week cycle.<br>* Other names: onalespib;Drug: abiraterone acetate<br>* 1000 mg PO daily.<br>Drug: Prednisone<br>* 5 mg PO twice daily.<br>* Other names: prednisolone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Safety and tolerability of the combination of AT13387 and abiraterone and to select the most promising treatment regimen in CRPC patients who are no longer responding to treatment with abiraterone alone. | Number of patients with adverse events Change in prostate specific antigen measurement and circulating tumor cell count every 4 weeks Change in tumor measurements by RECIST 1.1 every 12 weeks | 12 months | 
| Part B: Compare the antitumor activity (response rate per the Prostate Cancer Working Group 2 [PCWG2]) between single-agent AT13387 and combination of AT13387 plus abiraterone in patients who are no longer responding to treatment with abiraterone alone. | Change in prostate specific antigen measurement and circulating tumor cell count every 4 weeks Change in tumor measurements by RECIST 1.1 every 12 weeks | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of combination treatment of AT13387 and abiraterone. | Area under the plasma concentration versus time curve (AUC) of AT13387 and abiraterone alone and in combination by Week 4 Maximum concentration (Cmax) of AT13387 and abiraterone alone and in combination by Week 4 | 24 months | 
| Pharmacodynamics of combination treatment of AT13387 and abiraterone. | CTC enumeration and characterization every 4 weeks. | 24 months | 
| Progression free survival | Assessment of progression free survival as measured by weeks | 24 months | 
| Overall survival | Overall survival as measured in weeks | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer