Difluoromethylornithine and High Dose Testosterone With Enzalutamide in Metastatic Castration-Resistant Prostate Cancer

About This Trial

This clinical trial is testing a new treatment approach that alternates high doses of testosterone and a study drug called DFMO with a standard medicine called enzalutamide to help control cancer growth.
It is for adults with advanced prostate cancer that has spread and worsened after taking the hormone therapy abiraterone, but who do not currently have pain from their cancer.
Before considering this study, you should know that you cannot take strong opioid painkillers and may need to undergo small tissue samples (biopsies) to monitor your tumor.
Participants must also meet safety requirements, such as having no history of seizures or significant hearing loss, and must agree to use reliable birth control during the trial.

More Information

Asymptomatic patients with metastatic castrate resistant prostate cancer (mCRPC) without pain due to prostate cancer will be treated on an open label study to evaluate effectiveness of sequential treatment with the combination of difluoromethylornithine (DFMO) and high dose testosterone in sequence with enzalutamide to improve primary and secondary outcomes.

Who Can Enroll

Age Range: 18 years and older
Gender: Male
Who This Trial is For: This clinical trial is testing a new treatment approach that alternates high doses of testosterone and a study drug called DFMO with a standard medicine called enzalutamide to help control cancer growth.

Study Details

Start Date: October 4, 2023
Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Full Eligibility Criteria

Inclusion Criteria

Eastern Cooperative Oncology Group (ECOG) Performance status ≤2.
Age ≥18 years.
Histologically-confirmed adenocarcinoma of the prostate.
Treated with continuous androgen ablative therapy (either surgical castration or LHRH agonist/antagonist).
Documented castrate level of serum testosterone (4 weeks from last dose.
Prior treatment with bipolar androgen therapy (BAT) is allowed if the patient has progressed on an AR-axis inhibitor (i.e. abiraterone or antiandrogen) since BAT treatment.
Patients must be withdrawn from abiraterone for ≥ 2 weeks.
Attempts must be made to wean patients off prednisone prior to starting therapy. Patients who cannot be weaned due to symptoms may continue on lowest dose of prednisone achieved during weaning period.
Acceptable liver function:
- Bilirubin < 2.5 times institutional upper limit of normal (ULN)
- Aspartate transaminase (AST) (SGOT) and alanine transaminase (AST) (SGPT) < 2.5 times ULN
Acceptable renal function: Glomerular filtration rate (GFR) of 50 mL/min/1.73 m2 or higher. GFR will be estimated by the 2021 chronic kidney disease epidemiology (CKD-EPI) creatinine equation (REF: Inker LA, Eneanya ND, Coresh J, et al. Chronic Kidney Disease Epidemiology Collaboration. New Creatinine- and Cystatin C-Based Equations to Estimate GFR without Race. N Engl J Med 2021; 385:1737) using the online calculator found on UpToDate (https://www.uptodate.com/contents/calculator-glomerular-filtration-rate-gfr-by-ckd- epiequation-in-adults-conventional-and-si-units search=gfr&topicRef=2359&source=see_link).
Acceptable hematologic status:
- Absolute neutrophil count (ANC) ≥ 1500 cells/mm3 (1.5 ×109/L)
- Platelet count ≥ 100,000 platelet/mm3 (100 ×109/L)
- Hemoglobin ≥ 8 g/dL.
Ability to understand and willingness to sign a written informed consent document.
Sexually active participants with female partners of childbearing potential are eligible to participate if they agree to follow 1 of the following methods of contraception consistently, starting from screening, during the study and for at least 3 months after the last dose of DFMO and/or enzalutamide:
- Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a longterm and persistent basis) and agree to remain abstinent.
- Are sterilized (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate);
- Agree to use a male condom and have their partner use a contraceptive method with a failure rate of 51%, untreated severe obstructive sleep apnea, uncontrolled or poorly controlled heart failure [per Endocrine Society Clinical Practice Guidelines (34)]
Patients allergic to sesame seed oil or cottonseed oil are excluded.
Major surgery (i.e., requiring general anesthesia) within 3 weeks before screening, or has not fully recovered from prior surgery (i.e., unhealed wound). Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.
Subjects with significant hearing loss defined as hearing loss that affects everyday life and/or for which a hearing aid is required.
Patients with history of seizure or any condition that may predispose to seizure (e.g., prior cortical stroke or significant brain trauma, brain arteriovenous malformation)