NCT05593497

A Single-Arm Phase II Study of Neoadjuvant Intensified Androgen Deprivation (Leuprolide and Abiraterone Acetate) in Combination With AKT Inhibition (Capivasertib) for High-Risk Localized Prostate Cancer With PTEN Loss

Precision Neoadjuvant Therapy for High Risk Localized Prostate Cancer With PTEN Loss

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: VA Office of Research and Development · Federal
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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 mortality has been the focus of prostate cancer systemic therapy for decades; however, PTEN loss is a lead mechanism for prostate cancer resistance to AR directed therapy and development of castrate resistant prostate cancer. Pre-clinical research identified a reciprocal feedback regulation between the PTEN/AKT signaling axis and the Androgen Receptor (AR) signaling axis. Thus, blockade of both pathways may be necessary in tumors with PTEN loss. This study will change standard localized treatment (radical prostatectomy alone) by conducting a single arm Phase II trial combining intensified androgen deprivation (iADT; abiraterone and leuprolide) with an AKT inhibitor (capivasertib) prior to radical prostatectomy among high-risk localized prostate cancers with PTEN loss. The goal is that early precision treatment of aggressive disease will result minimal residual cancer at the time of prostatectomy, and subsequently improved cancer outcomes. Eligible patients with high-risk prostate cancer exhibiting 10% PTEN staining by IHC will be exposed to a 4-week run-in of iADT, followed by dedicated research biopsy of the tumor to be used for correlative research, then treated with 16 weeks of combined iADT with AKT inhibition (capivasertib). Patients will then undergo radical prostatectomy as standard of care, with assessment of pathological response (pT0 or minimal residual disease) via central pathology review.

Conditions

• High-Risk Prostate Cancer

Interventions

Type	Name	Description
DRUG	Capivasertib	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).
DRUG	abiraterone acetate	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.

Timeline

• Start date: 2024-05-31
• Primary completion: 2027-05-01
• Completion: 2027-08-01
• First posted: 2022-10-25
• Last updated: 2026-03-27

Locations

6 sites across 1 country: United States

Regulatory

• FDA-regulated drug study