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Prostate CancerPhase 2NCT06059118

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

A Phase 2 study testing DFMO, testosterone cypionate and Luteinizing hormone-releasing hormone (LHRH) analogue in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostate Cancer
What is being tested?
DFMO, testosterone cypionate and Luteinizing hormone-releasing hormone (LHRH) analogue
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
4 Oct 2023to 30 Nov 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 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=seelink).
  • 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 <1% per year as described below when having penile-vaginal intercourse with a woman of childbearing potential who is not currently pregnant, and who agrees to the use of a condom by her partner.
  • In addition, participants must refrain from donating sperm starting from Screening, during the study and for at least 3 months after the last dose of DFMO and/or enzalutamide.
  • Sexually active participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse; or use a male condom during each episode of penile penetration during the study
  • Patients with soft-tissue disease amenable to biopsy as determined by Interventional Radiology must agree to serial biopsies as per the study schedule to be eligible.

Who cannot join

  • 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.
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  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Laura Sena, MD, PhD contact

410-502-3825

laura.sena@jhmi.edu

Kathy Schultz, RN contact

410-614-9482

kschult3@jhmi.edu

United States1 site, 1 recruiting

  • Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21287

    Kathy Schultz, RN, 410-614-9482, kschult3@jhmi.edu

    Laura Sena, MD,PhD

    Recruiting

Other trials in United States

About this study

Official title: Repeat Difluoromethylornithine and High Dose Testosterone With Enzalutamide in Asymptomatic Patients With Metastatic Castration-Resistant Prostate Cancer: The APEX (Androgen and Polyamine Elimination Alternating With Xtandi) Trial

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.

Read the detailed description

Eligible patients are those with mCRPC who have progressive disease after treatment with Abiraterone (Abi) used as treatment for castration-sensitive or castration-resistant disease. Patients will continue on androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone (LHRH) agonist (i.e. Zoladex, Trelstar, Eligard, or Lupron) or LHRH antagonist (Degarelix or Relugolix) if not surgically castrated throughout the duration of the study to inhibit endogenous testosterone production. One cycle of treatment will be 119 days and will involve:

  1. 7 days of DFMO at a dose of 1000 mg PO BID (D1-D7), followed by
  2. 56 days of combined testosterone and DFMO (testosterone cypionate 400 mg IM on D8 and D36 with continued DFMO 1000 mg PO BID) (D8-D63), followed by
  3. 56 days of enzalutamide (enzalutamide 160 mg PO daily) (D64-D119)

Patients will receive repeat cycles of treatment until clinical or radiographic progression or toxicity requiring drug cessation.

Conditions
Prostate Cancer
Being tested
DFMO, testosterone cypionate, Luteinizing hormone-releasing hormone (LHRH) analogue, Enzalutamide
Keywords
prostate cancer, metastatic prostate cancer, DFMO, Enzalutamide, High dose testosterone
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DFMODrug

    Also called eflornithine, difluoromethylornithine

    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.

  • testosterone cypionateDrug

    Also called DEPO-Testosterone Injection

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

  • Luteinizing hormone-releasing hormone (LHRH) analogueDrug

    Also called Zoladex, Trelstar, Eligard, Lupron

    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.

  • EnzalutamideDrug

    Also called Xtandi

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

Study groups in NCT06059118
Study groupRoleWhat they receive
Repeat Sequential DFMO and High dose Testosterone in Sequence with EnzalutamideExperimentalEligible 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).
Receives: Drug: DFMO; Drug: testosterone cypionate; Drug: Luteinizing hormone-releasing hormone (LHRH) analogue; Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PSA response rate at Cycle 1 Day 64

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

    Measured: Cycle 1 Day 64 (each cycle is 119 days)

Secondary outcomes (7)

  1. Progression-free survival

    Time to radiographic or clinical progression or death.

    Measured: 3 years after end of treatment

  2. PSA response rate at any timepoint

    Number of participants with >50% PSA decline from baseline at any point on trial.

    Measured: up to 13 months

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

    Number of participants who experience adverse events grade 3 or high and serious adverse events, as defined by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

    Measured: 13 months

  4. PSA progression-free survival (PSA-PFS)

    Time from the date of first dose to the time of PSA progression.

    Measured: up to 13 months

  5. Measurable disease response rate

    Number of participants with measurable disease with complete response or partial response per RECIST 1.1.

    Measured: 13 months

  6. Pain Score

    The modified Patient-Reported Outcomes Measurement Information System (PROMIS) short form (SF) (v1.0 short forms 3a and 6b) pain scale is a validated self-reported instrument assessing average pain intensity and interference over the past 7-day period. Possible scores for each pain intensity questions range from 1 (no pain) to 5 (very severe) with higher scores reflecting higher pain intensity. Possible scores for each pain interference range from 1 (not at all) to 5 (very much) with higher scores reflecting higher pain interference.

    Measured: Up to 12 months

  7. Pain Score Change

    Number of participants with changes in pain scores between baseline and post-treatment. Positive change scores are indicative of improvement in pain.

    Measured: Baseline, Up to 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Sep 2023
  2. Study start4 Oct 2023
  3. Primary completion4 Jan 2027 (estimated)
  4. Study completion30 Nov 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06059118
Sponsor's protocol ID
J2326
Other IDs
IRB00371517
Status last verified
Jan 2026
First submitted
15 Sep 2023
Last updated
14 Jan 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing DFMO, testosterone cypionate and Luteinizing hormone-releasing hormone (LHRH) analogue in people with Prostate Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 32 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Laura Sena, MD, PhD (410-502-3825, laura.sena@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PSA response rate at Cycle 1 Day 64 (time frame: Cycle 1 Day 64 (each cycle is 119 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06059118.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.

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