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

NCT05593497 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: SPLP-001-21F
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

High-Risk Prostate Cancer

Keywords

veterans; prostate cancer; PTEN protein; prostatectomy; neoadjuvant therapy; abiraterone acetate; capivasertib; leuprolide

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response or Minimal Residual Disease (MRD)

  No cancer detected on radical prostatectomy specimen, or minimal residual disease 5mm.

  5 months

Secondary Outcomes (2)

• Surgical Complications

  5 months + 90 days

• ERG Expression and Pathologic Response

  5 months

Other Outcomes (1)

• Treatment related adverse events

  5 months + 90 days

Study Arms (1)

Single Arm

EXPERIMENTAL

neoadjuvant capivasertib combined with androgen receptor pathway therapy (leuprolide + abiraterone) prior to radical prostatectomy

Drug: Capivasertib; Drug: abiraterone acetate

Interventions

Capivasertib DRUG

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).

Single Arm

abiraterone acetate DRUG

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.

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age greater than or equal to 18 years. Members of all races and ethnic groups will be included.
• Participants must have histologically confirmed non-metastatic adenocarcinoma of the prostate
• (a) Any one of the following three high risk features:
• Gleason sum \>7 (ISUP Grade Group \>3)
• Clinical stage T3 (resectable), per AJCC Cancer Staging Manual, 8th ed.
• Gleason score 4+3=7 (ISUP Grade Group 3) AND
• Estimated progression-free probability after radical prostatectomy that is less than or equal to 50% at 5 years by MSK nomogram
• No definitive evidence of metastasis on nuclear bone scan (required on all subjects)
• No evidence of lymph nodes \> 2 cm in diameter on pelvic CT scan (scan only required in patients with a PSA \> 20 ng/ml)
• Prostatectomy with extended lymph node dissection planned as primary therapy.
• The subject had a discussion with a clinician about other options, such as radiotherapy, and elected to undergo surgical treatment.
• The subject has been offered consultation with radiation oncology and declined consultation or radiation treatment, or determined it was not in best medical interest
• Be willing to provide tissue from a diagnostic biopsy core or excisional biopsy of a tumor lesion obtained up to 6 months/180 days prior to initiation of treatment on Day 1. Subjects for whom samples cannot be provided (e.g., inaccessible or subject safety concern) may submit an older archived specimen only upon agreement from the Sponsor-Investigator.
• Tumor tissue must be provided for biomarker analysis. PTEN IHC staining must be less than or equal to 10% as determined by the central lab. If insufficient tumor tissue content is provided for analysis, acquisition of additional archived tumor tissue (block and /or slides) for the biomarker analysis is required.

You may not qualify if:

• As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant and active bleeding diseases, uncontrolled pulmonary, renal, or hepatic dysfunction, uncontrolled infection, cardiac disease) which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol.
• Any other disease, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, may affect the interpretation of the results, render the patient at high risk from treatment complications or interferes with obtaining informed consent.
• Known to have active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening. Known to have human immunodeficiency virus (HIV) with a CD4+ T-cell count \< 350 cells/uL or a history of an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the past 12 months. Known to have active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
• Known history of drug or alcohol abuse within 6 months of screening.
• Prior prostate cancer treatment including:
• Anti-androgen therapy including orchiectomy, LHRH therapy, abiraterone, ketoconazole, estrogen therapy (Short-term ADT allowed, less than or equal to 2 months)
• Radiation (external beam or brachytherapy)
• Cytotoxic chemotherapy
• Focal or ablative therapy
• Any experimental therapy for treatment of prostate cancer.
• History of another primary malignancy except for malignancy treated with curative intent with no known active disease greater than or equal to 5 years before the first dose of study intervention and of low potential risk for recurrence. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that has undergone potentially curative therapy
• Any of the following cardiac criteria:
• Mean resting corrected QT interval (QTc) \> 470 msec obtained from 3 consecutive ECGs
• Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g., complete left bundle branch block, third-degree heart block)
• Medical history significant for arrhythmia (e.g., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted to enter the study

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (6)

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, 90073-1003, United States

RECRUITING

James J. Peters VA Medical Center, Bronx, NY

The Bronx, New York, 10468-3904, United States

RECRUITING

VA Portland Health Care System, Portland, OR

Portland, Oregon, 97207-2964, United States

RECRUITING

Ralph H. Johnson VA Medical Center, Charleston, SC

Charleston, South Carolina, 29401-5703, United States

RECRUITING

South Texas Health Care System, San Antonio, TX

San Antonio, Texas, 78229-4404, United States

TERMINATED

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, 98108-1532, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

capivasertib; Abiraterone Acetate

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Ryan P Kopp, MD

  VA Portland Health Care System, Portland, OR

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ryan P Kopp, MD

CONTACT

(503) 220-8262; ryan.kopp@va.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 20, 2022
• First Posted: October 25, 2022
• Study Start: May 31, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)