VA Office of Research and Development
The purpose of this study is to learn about how an investigational drug intervention completed before doing prostate surgery (specifically, radical prostatectomy with lymph node dissection) may help in treatment of high risk localized prostate cancers that are most resistant to standard treatments. This is a phase II research study. For this study, capivasertib, the study drug, will be taken with intensified androgen deprivation drugs (iADT; abiraterone and leuprolide) prior to radical prostatectomy. This study drug treatment will be evaluated to see if it is effective in shrinking and destroying prostate cancer tumors prior to surgery and to further evaluate its safety prior to prostate cancer surgery.
Prostate cancer is the second leading cause of cancer deaths in men in the United States. Prostate cancer treatment options are historically based on clinical stage, prostate specific antigen (PSA) blood test, and tumor grade. High-risk prostate cancers treated surgically commonly exhibit loss of the phosphatase and tensin homologue (PTEN) tumor suppressor gene, which leads to increased activity of the AKT signaling pathway. PTEN loss is associated with higher rates of prostate cancer recurrence, metastasis, and cancer mortality. Manipulation of androgens and androgen receptor (AR) to reduce m…
Inclusion Criteria: 1. Informed Consent: provision of signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. 2. Members of all races and ethnic groups will be included. 3. Participants must have histologically confirmed non-metastatic adenocarcinoma of the prostate 4. (a) Any one of the following three high risk features: * Gleason sum \>7 (ISUP Grade Group \>3) * Clinical stage T3 (resectable), per American Joint Committee on Cancer (AJCC) Cancer Staging Manual, 8th edition * Prostate…
400 mg (2 tablets) BID given on an intermittent weekly dosing schedule. Patients will be dosed on Days 1 to 4 in each week (4 days on, 3 days off). Treatment will be given in combination with abiraterone for 16 weeks duration (+/- 1 week for surgery window).
Administered orally as tablets at a dosage of 1000 mg daily. To be administered with prednisone 5mg po daily. Subjects will be on concurrent GNRH agonist therapy (leuprolide, administered as standard of care). Intensified androgen deprivation (iADT) consisting of abiraterone and leuprolide will be administered for a 4 week run-in prior to addition of capivasertib.