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

NCT05574712 | Withdrawn Phase 2

• 2 other identifiers: J2258IRB00338335
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Prostate Cancer

Keywords

prostate; prostate cancer; neoadjuvant; therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  12 weeks

Secondary Outcomes (5)

• Negative Margin Rate

  12 weeks

• Rate of Pathologic T3 disease

  12 weeks

• Rate of radiographic disappearance of prostate nodules

  12 weeks

• Proportion of participants receiving adjuvant radiation therapy

  Up to 1 year after prostatectomy

• Biochemical progression measured by Prostate Specific Antigen (PSA)

  2 years

Other Outcomes (1)

• Overall Survival Estimate of Participants

  2 years

Study Arms (1)

Open-Label Treatment Group

EXPERIMENTAL

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

Interventions

Neoadjuvant treatment 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

Also known as: leuprolide acetate, abiraterone acetate, belzutifan

Open-Label Treatment Group

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Neoadjuvant Therapy; Leuprolide; Abiraterone Acetate; belzutifan

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Ken Pienta, M.D

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: October 6, 2022
• First Posted: October 10, 2022
• Study Start: January 1, 2024
• Primary Completion: January 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 18, 2024

Record last verified: 2024-03