A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate
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Purpose
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).
| Condition | Intervention | Phase |
|---|---|---|
|
Prostate Cancer |
Drug: AT13387 and abiraterone Drug: AT13387 alone |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | 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 |
- 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. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
- 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. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- 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
- Pharmacokinetics of combination treatment of AT13387 and abiraterone. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- 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. [ Time Frame: 24 months ] [ Designated as safety issue: No ]CTC enumeration and characterization every 4 weeks.
- Progression free survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]Assessment of progression free survival as measured by weeks
- Overall survival [ Time Frame: 24 months ] [ Designated as safety issue: No ]Overall survival as measured in weeks
| Estimated Enrollment: | 164 |
| Study Start Date: | September 2012 |
| Estimated Study Completion Date: | January 2015 |
| Estimated Primary Completion Date: | September 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: AT13387 and abiraterone
Part A: AT13387 IV with abiraterone 1000 mg QD and prednisone or prednisolone 5 mg BID
|
Drug: AT13387 and abiraterone
Parallel
Other Name: AT13387 and Zytiga
|
|
Experimental: AT13387 alone or in combination with abiraterone acetate
Part B: AT13387 alone or AT13387 with abiraterone acetate 1000 mg PO
|
Drug: AT13387 alone
Parallel
Other Name: AT13387
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Contact: Medpace Recruitment Center | 1.866.872.2349 | recruitment@medpace.com |
Show 40 Study Locations| Principal Investigator: | Johann De Bono, MD | Royal Marsden Foundation Trust Institute of Cancer Research |
More Information
No publications provided
| Responsible Party: | Astex Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01685268 History of Changes |
| Other Study ID Numbers: | AT13387-04 |
| Study First Received: | August 31, 2012 |
| Last Updated: | April 24, 2013 |
| Health Authority: | United States: Food and Drug Administration Canada: Health Canada United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by Astex Pharmaceuticals:
|
Prostate Cancer |
Additional relevant MeSH terms:
|
Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site |
Neoplasms Genital Diseases, Male Prostatic Diseases |
ClinicalTrials.gov processed this record on May 19, 2013