A Neoadjuvant Study of Abiraterone Acetate, Leuprolide Acetate, and Belzutifan in Men With Regional Prostate Cancer

NCT ID: NCT05574712

Last Updated: 2024-03-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-01
• Study Completion Date: 2026-07-31

Brief Summary

For men with prostate cancer that involves the nearby lymph nodes (N1) standard treatment varies. Many men undergo radical prostatectomy (total removal of the prostate) along with the removal of nearby lymph nodes. Other men may opt for androgen deprivation therapy (ADT, a therapy that blocks testosterone) using the two drugs leuprolide and abiraterone - with or without radiation. This research is being done to investigate whether the use of leuprolide and abiraterone, when given in combination with a drug that blocks a molecule that senses oxygen needs by cancer cells, belzutifan, can kill cancer cells in the body prior in men who are planning on having the prostate surgically removed.

Detailed Description

Eligible participants will receive 1 dose of leuprolide on day 1 as a subcutaneous injection and abiraterone and belzutifan as pills to take every day for 89 days. Participants will then undergo radical prostatectomy as a standard of care to treat prostate cancer approximately 2 weeks after finishing the study drugs. Participants will have PSA checked 1 year and 2 years after surgery. The list of study procedures (some of which are likely to be part of regular cancer care) will include the collection of data from medical records, imaging tests (CT/MRI/ Prostate-Specific Membrane Antigen Scan PSMA/ Positron Emission Tomography PET CT) to evaluate tumors, and blood collection.

Conditions

Prostate Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open-Label Treatment Group

Participants will be treated with neoadjuvant therapy for a total of 3 months (12 weeks) prior to prostatectomy. Therapy will consist of leuprolide acetate, abiraterone acetate, and belzutifan.

Group Type: EXPERIMENTAL

Neoadjuvant treatment

Intervention Type: DRUG

Each drug will be dosed at its respective FDA-approved dose. These dosages are as follows: leuprolide acetate 22.5 mg depot injection x one dose, abiraterone acetate 1000 mg by mouth daily, and belzutifan120 mg administered by mouth once daily. All men will also be treated with prednisone 5 mg by mouth twice daily while on abiraterone acetate in order to blunt its associated mineralocorticoid side effects

Interventions

Neoadjuvant treatment

Each drug will be dosed at its respective FDA-approved dose. These dosages are as follows: leuprolide acetate 22.5 mg depot injection x one dose, abiraterone acetate 1000 mg by mouth daily, and belzutifan120 mg administered by mouth once daily. All men will also be treated with prednisone 5 mg by mouth twice daily while on abiraterone acetate in order to blunt its associated mineralocorticoid side effects

Intervention Type: DRUG

Other Intervention Names

leuprolide acetate; abiraterone acetate; belzutifan

Eligibility Criteria

Inclusion Criteria

1. Willing and able to provide written informed consent.

2. Age ≥ 18 years

3. Eastern cooperative group (ECOG) performance status ≤2

4. Documented histologically confirmed adenocarcinoma of the prostate

5. Willing to undergo prostatectomy as primary treatment for localized prostate cancer

6. Regional prostate cancer (per National Comprehensive Cancer Network criteria): T1-4, N1, M0. Patients with negative conventional imaging may have regional prostate cancer defined by PSMA PET imaging.

7. Serum testosterone ≥150 ng/dL

8. Able to swallow the study drugs whole as tablets

9. Willing to take abiraterone acetate on an empty stomach (no food should be consumed at least two hours before and for one hour after dosing).

10. Willing to use a condom if having sex with a pregnant woman, or use a condom and another effective method of birth control if having sex with a woman of childbearing potential. These measures are required during and for one week after treatment with abiraterone acetate.

Exclusion Criteria

1. Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)

2. Prior use of enzalutamide, apalutamide, darolutamide or abiraterone acetate

3. Prior or ongoing systemic therapy for prostate cancer including, but not limited to:

1. androgen deprivation therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)

2. Cytochrome CYP-17 inhibitors (e.g. ketoconazole)

3. Treatment with 1st generation antiandrogen (e.g. bicalutamide) allowed if less than one month of therapy

4. Immunotherapy (e.g. sipuleucel-T, ipilimumab)

5. Chemotherapy (e.g. docetaxel, cabazitaxel)

4. Evidence of serious and/or unstable pre-existing medical, psychiatric, or other conditions (including laboratory abnormalities) that could interfere with patient safety or the provision of informed consent to participate in this study.

5. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.

6. Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL]

7. Abnormal liver function (bilirubin, Aspartate transaminase (AST), Alanine Transaminase (ALT) ≥ 3 x upper limit of normal)

8. Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal)

9. Abnormal cardiac function as manifested by the New York Heart Association (NYHA) class III or IV heart failure or history of a prior myocardial infarction (MI) within the last five years before enrollment in the study.

10. History of prior cardiac arrhythmia

11. Baseline pulse oximetry of <90%

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ken Pienta, M.D

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Other Identifiers

IRB00338335

Identifier Type: OTHER

Identifier Source: secondary_id

J2258

Identifier Type: -

Identifier Source: org_study_id