Prostate Cancer
Conditions
Keywords
Prostate Cancer
Brief summary
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).
Interventions
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.
1000 mg PO daily.
5 mg PO twice daily.
Sponsors
Study design
Eligibility
Inclusion criteria
Inclusion: 1. Must have prostate cancer 2. Have received prior castration by orchiectomy and/or hormone therapy 3. Males \>18 years of age 4. Normal activity level for self care 5. Have been receiving abiraterone therapy with a steroid for ≥1 month 6. Have disease progression on abiraterone as defined by either PSA progression, radiographic or bone progression 7. Have adequate bone marrow, liver and kidney function 8. 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 9. Must be willing and able to provide written informed consent and comply with the protocol and study procedures Exclusion: 1. Prior anti-cancer treatment with any Heat Shock Protein 90 (HSP90) inhibitor or histone deacetylase (HDAC) inhibitor compound 2. Have received chemotherapy within 4 weeks prior to receiving study drug 3. Prior prostate surgery or radiotherapy within 4 weeks from the first dose of study drug 4. Hypersensitivity to AT13387 or other components of the drug product 5. Treatment with any investigational drug within 4 weeks prior to the first dose of study drug 6. Severe systemic diseases or active uncontrolled infections 7. Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors 8. Abnormal heart function 9. 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; 10. No known brain or CNS involvement 11. Unable to receive corticosteroids or history of pituitary or adrenal dysfunction 12. Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 12 months | * 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 |
| 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. | 12 months | * 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics of combination treatment of AT13387 and abiraterone. | 24 months | * 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 |
| Pharmacodynamics of combination treatment of AT13387 and abiraterone. | 24 months | CTC enumeration and characterization every 4 weeks. |
| Progression free survival | 24 months | Assessment of progression free survival as measured by weeks |
| Overall survival | 24 months | Overall survival as measured in weeks |
Countries
Canada, Spain, United Kingdom, United States