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

Primary Purpose

Prostate Cancer

Status

Not yet recruiting

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Neoadjuvant treatment

About this trial

This is an interventional treatment trial for Prostate Cancer focused on measuring prostate, prostate cancer, neoadjuvant, therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Willing and able to provide written informed consent.
Age ≥ 18 years
Eastern cooperative group (ECOG) performance status ≤2
Documented histologically confirmed adenocarcinoma of the prostate
Willing to undergo prostatectomy as primary treatment for localized prostate cancer
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.
Serum testosterone ≥150 ng/dL
Able to swallow the study drugs whole as tablets
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).
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:

Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy)
Prior use of enzalutamide, apalutamide, darolutamide or abiraterone acetate
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)
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.
Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule.
Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL]
Abnormal liver function (bilirubin, Aspartate transaminase (AST), Alanine Transaminase (ALT) ≥ 3 x upper limit of normal)
Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal)
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.
History of prior cardiac arrhythmia
Baseline pulse oximetry of <90%

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Open-Label Treatment Group

Arm Description

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.

Outcomes

Primary Outcome Measures

Rate of near pathological complete response (pCR)

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

Negative Margin Rate

The negative margin rate as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant treatment

Rate of Pathologic T3 disease

The rate of pathologic T3 disease as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant treatment.

Rate of radiographic disappearance of prostate nodules

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.

Proportion of participants receiving adjuvant radiation therapy

The proportion of men who receive adjuvant radiation therapy within 1-year of prostatectomy.

Biochemical progression measured by Prostate Specific Antigen (PSA)

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).

Full Information

NCT ID

NCT05574712

First Posted

October 6, 2022

Last Updated

July 27, 2023

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

1. Study Identification

Unique Protocol Identification Number

NCT05574712

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

January 1, 2024 (Anticipated)

Primary Completion Date

January 2025 (Anticipated)

Study Completion Date

July 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

Keywords

prostate, prostate cancer, neoadjuvant, therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Open-Label Treatment Group

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Neoadjuvant treatment

Other Intervention Name(s)

leuprolide acetate, abiraterone acetate, belzutifan

Intervention Description

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

Primary Outcome Measure Information:

Title

Rate of near pathological complete response (pCR)

Description

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Negative Margin Rate

Description

The negative margin rate as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant treatment

Time Frame

12 weeks

Title

Rate of Pathologic T3 disease

Description

The rate of pathologic T3 disease as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant treatment.

Time Frame

12 weeks

Title

Rate of radiographic disappearance of prostate nodules

Description

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.

Time Frame

12 weeks

Title

Proportion of participants receiving adjuvant radiation therapy

Description

The proportion of men who receive adjuvant radiation therapy within 1-year of prostatectomy.

Time Frame

Up to 1 year after prostatectomy

Title

Biochemical progression measured by Prostate Specific Antigen (PSA)

Description

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).

Time Frame

2 years

Other Pre-specified Outcome Measures:

Title

Overall Survival Estimate of Participants

Description

The overall survival estimate two years after the last patient has accrued.

Time Frame

2 years

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Willing and able to provide written informed consent. Age ≥ 18 years Eastern cooperative group (ECOG) performance status ≤2 Documented histologically confirmed adenocarcinoma of the prostate Willing to undergo prostatectomy as primary treatment for localized prostate cancer 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. Serum testosterone ≥150 ng/dL Able to swallow the study drugs whole as tablets 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). 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: Prior local therapy to treat prostate cancer (e.g. radical prostatectomy, radiation therapy, brachytherapy) Prior use of enzalutamide, apalutamide, darolutamide or abiraterone acetate Prior or ongoing systemic therapy for prostate cancer including, but not limited to: androgen deprivation therapy (e.g. leuprolide, goserelin, triptorelin, degarelix) Cytochrome CYP-17 inhibitors (e.g. ketoconazole) Treatment with 1st generation antiandrogen (e.g. bicalutamide) allowed if less than one month of therapy Immunotherapy (e.g. sipuleucel-T, ipilimumab) Chemotherapy (e.g. docetaxel, cabazitaxel) 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. Any psychological, familial, sociological, or geographical condition that could potentially interfere with compliance with the study protocol and follow-up schedule. Abnormal bone marrow function [absolute neutrophil count (ANC)<1500/mm3, platelet count <100,000/mm3, hemoglobin <9 g/dL] Abnormal liver function (bilirubin, Aspartate transaminase (AST), Alanine Transaminase (ALT) ≥ 3 x upper limit of normal) Abnormal kidney function (serum creatinine ≥ 2 x upper limit of normal) 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. History of prior cardiac arrhythmia Baseline pulse oximetry of <90%

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Dr. Ken Pienta, M.D.

Phone

410-502-3137

kpienta1@jhmi.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ken Pienta, M.D

Organizational Affiliation

Johns Hopkins University

Official's Role

Principal Investigator

12. IPD Sharing Statement

Learn more about this trial

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

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