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

Recruiting now · Phase 2

Conditions studied: High-Risk Prostate Cancer

In brief

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.

Key facts

Study ID

NCT05593497

Run by

VA Office of Research and Development

People needed

30

Starts

2024-05-31

Expected to finish

2027-08-01

Last updated by the study team

2026-03-27

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

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.
• PSA > 20 ng/ml oSubjects who meet high risk criteria solely by PSA (i.e., stage <T3 AND Gleason sum less than or equal to 7) must have a progression-free probability after radical prostatectomy that is less than or equal to 50% at 5 years as estimated by the Memorial Sloan Kettering (MSK) pre-radical prostatectomy nomogram: https://www.mskcc.org/nomograms/prostate/pre_op (b) Subjects not meeting high risk criteria that have the following combination may be screened for inclusion:
• 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.
• Have a performance status of 0 or 1 on the ECOG Performance Scale with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
• Life expectancy of greater than 10 years per the treating physician.
• Minimum body weight of 45 kg with minimum Body Mass Index (BMI) of 18.5
• Non-sterile men who are not totally sexually abstinent (i.e., refraining from heterosexual intercourse during the entire period of risk associated with study interventions) and intend to be sexually active with a women of childbearing potential partner must use a condom upon entering the study and until 16 weeks after the last dose of capivasertib. Contraception should be considered in females' partners of men taking capivasertib who are of childbearing potential
• Able and willing to swallow and retain oral medication
• Demonstrate adequate organ function as defined by laboratory parameters including ANC, platelets, hemoglobin, transaminases, albumin, hemoglobin A1C, CrCl or eGFR, PTT and INR (unless anticoagulated, then therapeutic range is acceptable). All screening labs should be performed within 30 days of treatment initiation

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
• Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, potential for torsades de pointes, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age, or any concomitant medication known to prolong the QT interval
• Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or NYHA or Class II to IV heart failure or cardiac ejection fraction measurement of < 50%
• Experience of any of the following procedures or conditions in the preceding 6 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, angina pectoris, congestive heart failure NYHA Grade less than or equal to 2
• Uncontrolled hypotension - systolic blood pressure (SBP) <90 mmHg and/or diastolic blood pressure (DBP) <50 mmHg
• Uncontrolled hypertension (SBP greater than or equal to 160 mmHg or DBP greater than or equal to 95 mmHg).
• Cardiac ejection fraction outside institutional range of normal or <50% (whichever is higher) as measured by echocardiogram (or multiple-gated acquisition [MUGA] scan if an echocardiogram cannot be performed or is inconclusive).
• Clinically significant abnormalities of glucose metabolism as defined by any of the following:
• Patients with diabetes mellitus type 1 or diabetes mellitus type 2 requiring insulin treatment
• HbA1c greater than or equal to 8.0% (63.9 mmol/mol)
• Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of capivasertib and abiraterone.

Where it is running

• VA Greater Los Angeles Healthcare System, West Los Angeles, CA — West Los Angeles, California, United States (enrolling)
• James J. Peters VA Medical Center, Bronx, NY — The Bronx, New York, United States (enrolling)
• VA Portland Health Care System, Portland, OR — Portland, Oregon, United States (enrolling)
• Ralph H. Johnson VA Medical Center, Charleston, SC — Charleston, South Carolina, United States (enrolling)
• VA Puget Sound Health Care System Seattle Division, Seattle, WA — Seattle, Washington, United States (enrolling)
• South Texas Health Care System, San Antonio, TX — San Antonio, Texas, United States

Full record on ClinicalTrials.gov

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