Neoadjuvant BKM120 in High-risk Prostate Cancer
|ClinicalTrials.gov Identifier: NCT01695473|
Recruitment Status : Active, not recruiting
First Posted : September 28, 2012
Last Update Posted : July 18, 2017
|Condition or disease||Intervention/treatment||Phase|
|High Risk Prostate Cancer||Drug: BKM120||Phase 2|
This is a phase II, prospective, pharmacodynamic study of BKM120 in high-risk, localized prostate cancer. After informed consent and central pathology review of the core prostate biopsy, eligible patients will be enrolled and scheduled to have an ultrasound-guided biopsy of the prostate to confirm high-risk disease and collect tissue for molecular analysis. Two weeks after the biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy at University of California, San Francisco. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy.
Up to 24 patients, or 21 evaluable patients, will be enrolled through the Department of Urology or Genitourinary Medical Oncology at the University of California, San Francisco for this pharmacodynamic study. Toxicity will be assessed during BKM120 administration, and will involve a clinic visit on Day 14 ± 2 (i.e. before surgery). Follow-up with safety evaluations will be at 90 ± 7 days post-operatively and involve a toxicity questionnaire, blood tests, and clinic visit. Toxicity will be monitored and reported using NCI Common Toxicity Criteria version 4.0 guidelines.
A patient symptom diary will be distributed to each patient at baseline for symptom self-recording and BKM120 dose self-administration. In addition, a patient identifier card (wallet-sized) will be distributed to each patient after informed consent and registration. This information will contain the patient's age, study name and number, investigator and study coordinator contact information, and expected adverse events that may be present as a result of BKM120 administration.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pharmacodynamic Study of Pre-prostatectomy BKM120 in Men With High-risk, Localized Prostate Cancer|
|Study Start Date :||October 2012|
|Actual Primary Completion Date :||February 2015|
|Estimated Study Completion Date :||December 2017|
Experimental: Neoadjuvant BKM120
Twenty four men will receive 2 weeks of daily BKM120 prior to having radical prostatectomy
Two weeks after confirmatory biopsy, patients will begin taking 100 mg/day of BKM120. BKM120 will be given at this dose level orally once daily for 14 days prior to radical prostatectomy. Radical prostatectomy will be performed on the day of the last dose of BKM120 at day 14. No further drug will be administered after radical prostatectomy. For unforeseen delays in OR scheduling, up to 7 additional days of BKM120 may be administered prior to surgery.
- PI3K inhibition in prostate tumor tissue [ Time Frame: 90-120 days ]Determine the proportion of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by phosphorylated S6 immunohistochemistry (ICH) when treated with 100 mg/day of BKM120 using paired tumor biopsies from before and after drug administration
- 4EBP1 protein [ Time Frame: 90-120 days ]Determine the proportion of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by 4EBP1 protein phosphorylation immunohistochemistry (IHC) using paired tumor biopsies from before and after drug administration
- BKM120 activity [ Time Frame: 90-120 days ]Evaluate the activity of short term BKM120 administration in prostate cancer as measured in PSA response immediately prior to surgery
- AKT protein [ Time Frame: 90-120 days ]Determine the proportion of men with downstream target inhibition of PI3K in prostate tumor tissue as measured by AKT protein phosphorylation immunohistochemistry (IHC)
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01695473
|United States, California|
|University of California, San Francisco|
|San Francisco, California, United States, 94115|
|Study Chair:||Charles Ryan, MD||University of California, San Francisco|