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

NCT06059118 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: J2326IRB00371517
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

prostate cancer; metastatic prostate cancer; DFMO; Enzalutamide; High dose testosterone

Outcome Measures

Primary Outcomes (1)

• PSA response rate at Cycle 1 Day 64

  Number of participants with \>50% PSA decline from baseline by Cycle 1 Day 64.

  Cycle 1 Day 64 (each cycle is 119 days)

Secondary Outcomes (7)

• Progression-free survival

  3 years after end of treatment

• PSA response rate at any timepoint

  up to 13 months

• Safety as assessed by number of participants experiencing adverse events grade 3 or higher and serious adverse events.

  13 months

• PSA progression-free survival (PSA-PFS)

  up to 13 months

• Measurable disease response rate

  13 months

Study Arms (1)

Repeat Sequential DFMO and High dose Testosterone in Sequence with Enzalutamide

EXPERIMENTAL

Eligible patients will receive 7 days of DFMO (1000 mg PO bid) (days 1-7 of cycle), followed by 56 days of combined testosterone (testosterone cypionate 400 mg IM on day 8 and day 36) and DFMO (1000 mg PO bid) (days 8-63 of cycle), followed by 56 days of enzalutamide (160 mg PO daily) (days 64-119).

Drug: DFMO; Drug: testosterone cypionate; Drug: Luteinizing hormone-releasing hormone (LHRH) analogue; Drug: Enzalutamide

Interventions

DFMO DRUG

Each 119 day cycle, Days 1-7 patient will take 1000 mg by mouth (PO) twice a day (bid), and then on Day 8 - 63 patient will take 1000 mg PO bid while receiving high dose testosterone IM on Day 8 and Day 36 of cycle.

Also known as: eflornithine, difluoromethylornithine

Repeat Sequential DFMO and High dose Testosterone in Sequence with Enzalutamide

testosterone cypionate DRUG

On Day 8 and Day 36 of each 119 day cycle, patient will receive high dose testosterone at 400 mg through intramuscular (IM) injection.

Also known as: DEPO-Testosterone Injection

Repeat Sequential DFMO and High dose Testosterone in Sequence with Enzalutamide

Enzalutamide DRUG

Each 119 day cycle, Days 64-119 patient will take 160 mg by mouth (PO) once a day (qd).

Also known as: Xtandi

Repeat Sequential DFMO and High dose Testosterone in Sequence with Enzalutamide

Luteinizing hormone-releasing hormone (LHRH) analogue DRUG

Patients who have progressive disease after treatment with Abiraterone (Abi) will continue with androgen depravation therapy (ADT) with LHRH analogue (LHRH agonist drug (i.e. Zoladex, Trelstar, Eligard or Lupron) or LHRH antagonist drug (Degarelix or Relugolix)). Dosing instructions will vary between the different LHRH analogues. Patients should follow the dosing instructions as directed by their physician.

Also known as: Zoladex, Trelstar, Eligard, Lupron, Degarelix, Relugolix

Repeat Sequential DFMO and High dose Testosterone in Sequence with Enzalutamide

Eligibility Criteria

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

You may qualify if:

• 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 (\<50 ng/dl).
• Metastatic disease radiographically documented by CT or bone scan.
• Must have had disease progression while on abiraterone acetate based on:
• PSA progression defined as an increase in PSA, as determined by 2 separate measurements taken at least 1 week apart And/ Or
• Radiographic disease progression, based on RECIST 1.1 in patients with measurable soft tissue lesions or Prostate Cancer Working Group 3 (PCWG3) for patients with bone disease
• Screening PSA must be ≥ 1.0 ng/mL.
• Patients with soft tissue lesion amenable to biopsy must agree to biopsy collection pre-treatment and at a defined point on treatment to perform tumor tissue analysis.
• Prior treatment with Provenge vaccine, 223Radium (Xofigo), Poly (ADP-ribose) polymerase (PARP) inhibitors, taxane chemotherapy, Lutetium prostate-specific membrane antigen (LuPSMA), antiandrogens (including enzalutamide, darolutamide, and apalutamide), and radiation is allowed if \>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.

You may not qualify if:

• Pain due to metastatic prostate cancer requiring treatment intervention with opioid pain medication.
• ECOG Performance status ≥3
• Requirement for urinary self-catheterization for voiding due to obstruction secondary to prostatic enlargement well documented to be due to prostate cancer or benign prostatic hyperplasia (BPH).
• Patients with indwelling Foley or suprapubic catheter for obstructive symptoms are eligible.
• Evidence of disease in sites or extent that, in the opinion of the investigator, would put the patient at risk from therapy with testosterone (e.g. femoral metastases with concern over fracture risk, severe and extensive spinal metastases with concern for spinal cord compression, extensive liver metastases).
• Active uncontrolled infection. Patients with a history of HIV/AIDS may be eligible if CD4+ T cell (a type of lymphocyte that helps coordinate the immune response against infection and disease) counts are ≥ 350 cell/ul, they have had no opportunistic infection within the past 12 months, they have been on established antiretroviral therapy (ART) for at least four weeks, the HIV viral load is less than 400 copies/ml prior to enrollment, and there is no significant drug-drug interaction with ART and the study drugs. Patients with chronic hepatitis B (HBV) infection with active disease who meet criteria for anti HBV therapy are eligible if they are on a suppressive antiviral therapy prior to enrollment and there is no drug-drug interaction with the study drugs. Patients with a history of hepatitis C (HCV) infection are eligible if they have completed curative antiviral treatment and the HCV viral load is below the limit of quantification.
• Any condition or mental impairment that may compromise the ability to give informed consent, patient's safety or compliance with study requirements as determined by the investigator.
• Patients receiving anticoagulation therapy with warfarin, rivaroxaban, or apixaban are not eligible for study. \[Patients on enoxaparin are eligible for study. Patients on warfarin, rivaroxaban, or apixaban, who can be transitioned to enoxaparin prior to starting study treatments will be eligible\].
• Patients are excluded with prior history of a thromboembolic event within the last 12 months that are not being treated with systemic anticoagulation.
• Hematocrit \>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)

Sponsors & Collaborators

• Panbela Therapeutics: collaborator
• Prostate Cancer Foundation: collaborator
• United States Department of Defense: collaborator
• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Eflornithine; testosterone 17 beta-cypionate; Gonadotropin-Releasing Hormone; Goserelin; Triptorelin Pamoate; luprolide acetate gel depot; Leuprolide; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; relugolix; enzalutamide

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)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Laura Sena, MD, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Sena, MD, PhD

CONTACT

410-502-3825; laura.sena@jhmi.edu

Kathy Schultz, RN

CONTACT

410-614-9482; kschult3@jhmi.edu

Study Design

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

Study Record Dates

• First Submitted: September 15, 2023
• First Posted: September 28, 2023
• Study Start: October 4, 2023
• Primary Completion (Estimated): January 4, 2027
• Study Completion (Estimated): November 30, 2029
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)