- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05574712
A Neoadjuvant Study of Abiraterone Acetate, Leuprolide Acetate, and Belzutifan in Men With Regional Prostate Cancer (J2258)
March 14, 2024 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
An Evolutionary Double Bind Phase II Neoadjuvant Study of Abiraterone Acetate, Leuprolide Acetate, and Belzutifan in Men With Regional Prostate Cancer Eligible for Prostatectomy
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.
Study Overview
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 Type
Interventional
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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%
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / 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.
|
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Negative Margin Rate
Time Frame: 12 weeks
|
The negative margin rate as assessed on prostatectomy specimens following 3-months (12 weeks) of neoadjuvant treatment
|
12 weeks
|
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.
|
12 weeks
|
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.
|
12 weeks
|
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.
|
Up to 1 year after prostatectomy
|
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).
|
2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Survival Estimate of Participants
Time Frame: 2 years
|
The overall survival estimate two years after the last patient has accrued.
|
2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Ken Pienta, M.D, Johns Hopkins University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Estimated)
January 1, 2024
Primary Completion (Estimated)
January 1, 2025
Study Completion (Estimated)
July 1, 2026
Study Registration Dates
First Submitted
October 6, 2022
First Submitted That Met QC Criteria
October 6, 2022
First Posted (Actual)
October 10, 2022
Study Record Updates
Last Update Posted (Actual)
March 18, 2024
Last Update Submitted That Met QC Criteria
March 14, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Genital Neoplasms, Male
- Prostatic Diseases
- Urogenital Diseases
- Male Urogenital Diseases
- Genital Diseases, Male
- Genital Diseases
- Prostatic Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Cytochrome P-450 Enzyme Inhibitors
- Hormone Antagonists
- Steroid Synthesis Inhibitors
- Reproductive Control Agents
- Fertility Agents, Female
- Fertility Agents
- Leuprolide
- Abiraterone Acetate
- Belzutifan
Other Study ID Numbers
- J2258
- IRB00338335 (Other Identifier: JHM IRB)
Drug and device information, study documents
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
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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