A Neoadjuvant Study of Abiraterone Acetate, Leuprolide Acetate, and Belzutifan in Men With Regional Prostate Cancer (J2258)

• ClinicalTrials.gov Identifier: NCT05574712
• Recruitment Status: Not yet recruiting
• First Posted: October 10, 2022
• Last Update Posted: October 21, 2022
• Sponsor: Johns Hopkins University
• Information provided by (Responsible Party): Johns Hopkins University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Neoadjuvant treatment	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment

Intervention Model Description

This is an evolutionary double bind, open-label, multi-site, Phase II neoadjuvant study in men with regional prostate cancer planning to undergo prostatectomy. This study will assess the rate of near pathological complete response (pCR) after 3 months (12 weeks) of neoadjuvant treatment with leuprolide acetate, abiraterone acetate, and belzutifan as assessed on prostatectomy specimens.

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. 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.

• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Evolutionary Double Bind Phase II Neoadjuvant Study of Abiraterone Acetate, Leuprolide Acetate, and Belzutifan in Men With Regional Prostate Cancer Eligible for Prostatectomy
• Estimated Study Start Date: January 2023
• Estimated Primary Completion Date: January 2024
• Estimated Study Completion Date: July 2025

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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.

Drug: 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; Other Names: leuprolide acetate; abiraterone acetate; belzutifan

Outcome Measures

Primary Outcome Measures :

1. Rate of near pathological complete response (pCR) [ Time Frame: 12 weeks ]
   The rate of near pathological complete response (i.e. ≤5 mm of residual tumor) as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant leuprolide acetate, abiraterone acetate, and belzutifan.

Secondary Outcome Measures :

1. Negative Margin Rate [ Time Frame: 12 weeks ]
   The negative margin rate as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant treatment
2. Rate of Pathologic T3 disease [ Time Frame: 12 weeks ]
   The rate of pathologic T3 disease as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant treatment.
3. Rate of radiographic disappearance of prostate nodules [ Time Frame: 12 weeks ]
   Rate of radiographic disappearance of MRI detectable significant prostate nodules (i.e. ≥0.5 cm in size) following 3-months (12 weeks) of neoadjuvant treatment.
4. Proportion of participants receiving adjuvant radiation therapy [ Time Frame: Up to 1 year after prostatectomy ]
   The proportion of men who receive adjuvant radiation therapy within 1-year of prostatectomy.
5. Biochemical progression measured by Prostate Specific Antigen (PSA) [ Time Frame: 2 years ]
   The biochemical (i.e. PSA) progression free survival estimate two years after the last patient has accrued (i.e. confirmed PSA post-radical prostatectomy ≥0.2 ng/mL).

Other Outcome Measures:

1. Overall Survival Estimate of Participants [ Time Frame: 2 years ]
   The overall survival estimate two years after the last patient has accrued.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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%

Contacts and Locations

Contacts

Contact: Dr. Ken Pienta, M.D.; 410-502-3137; kpienta1@jhmi.edu

Sponsors and Collaborators

Johns Hopkins University

Investigators

• Principal Investigator: Ken Pienta, M.D; Johns Hopkins University

More Information

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT05574712
• Other Study ID Numbers: IRB00338335
• First Posted: October 10, 2022
• Last Update Posted: October 21, 2022
• Last Verified: October 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Johns Hopkins University:

prostate; prostate cancer; neoadjuvant; therapy

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Leuprolide; Abiraterone Acetate; Fertility Agents, Female; Fertility Agents; Reproductive Control Agents; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors