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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
49
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.
University of California, Los Angeles Institute of Urologic Oncology
Los Angeles, California, United States
Stanford Cancer Center
Stanford, California, United States
Holy Cross Hospital
Fort Lauderdale, Florida, United States
Florida Cancer Specialists-Fort Myers
Fort Myers, Florida, United States
Lakeland Regional Cancer Center
Lakeland, Florida, United States
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
Time frame: 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
Time frame: 12 months
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
Time frame: 24 months
Pharmacodynamics of combination treatment of AT13387 and abiraterone.
CTC enumeration and characterization every 4 weeks.
Time frame: 24 months
Progression free survival
Assessment of progression free survival as measured by weeks
Time frame: 24 months
Overall survival
Overall survival as measured in weeks
Time frame: 24 months
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Southern Illinois University School of Medicine
Springfield, Illinois, United States
University of Maryland, Greenebaum Cancer Center
Baltimore, Maryland, United States
Center for Cancer & Blood Disorders
Bethesda, Maryland, United States
Washington University School of Medicine
St Louis, Missouri, United States
University of Nebraska Medical Center
Omaha, Nebraska, United States
...and 22 more locations