A Study of HSP90 Inhibitor AT13387 Alone or in Combination With Abiraterone Acetate
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT01685268
- Lead Sponsor
- Astex Pharmaceuticals, Inc.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 49
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A, Regimen 1 AT13387 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. Part A, Regimen 2 AT13387 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. Part A, Regimen 1 abiraterone acetate 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. Part A, Regimen 1 Prednisone 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. Part A, Regimen 2 Prednisone 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. Part A, Regimen 2 abiraterone acetate 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.
- Primary Outcome Measures
Name Time Method 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 weeksPart 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 Outcome Measures
Name Time Method Pharmacodynamics of combination treatment of AT13387 and abiraterone. 24 months CTC enumeration and characterization every 4 weeks.
Overall survival 24 months Overall survival as measured in weeks
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 4Progression free survival 24 months Assessment of progression free survival as measured by weeks
Trial Locations
- Locations (32)
The West Clinic
🇺🇸Memphis, Tennessee, United States
Clinical Research Alliance, Inc.
🇺🇸Lake Success, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
University of Maryland, Greenebaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Nottingham University Hospitals
🇬🇧Nottingham, United Kingdom
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Holy Cross Hospital
🇺🇸Fort Lauderdale, Florida, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Brighton & Sussex University Hospitals NHS Trust
🇬🇧Brighton, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
Centre hospitalier de l'Universite de Montreal (CHUM)
🇨🇦Montreal, Quebec, Canada
Royal Marsden Foundation Trust Instute of Cancer Researrch
🇬🇧London, United Kingdom
Velindre Cancer Center
🇬🇧Cardiff, United Kingdom
University Hospital Southampton
🇬🇧Southampton, United Kingdom
Northwest Medical Specialists, PLLC
🇺🇸Tacoma, Washington, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
University of California, Los Angeles Institute of Urologic Oncology
🇺🇸Los Angeles, California, United States
Florida Cancer Specialists-Fort Myers
🇺🇸Fort Myers, Florida, United States
Lakeland Regional Cancer Center
🇺🇸Lakeland, Florida, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Center for Cancer & Blood Disorders
🇺🇸Bethesda, Maryland, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Wirral, United Kingdom
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
The Christie Hospital NHS Trust
🇬🇧Manchester, United Kingdom
Charing Cross Hospital
🇬🇧London, United Kingdom
University of Surrey
🇬🇧Guildford, United Kingdom