Testosterone + Darolutamide for Prostate Cancer

Overseen By Donna Bieg, RN

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Warfarin, Coumadin

Disqualifiers: Unstable medical condition, Heart failure, Infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach for treating metastatic prostate cancer by alternating between testosterone therapy (testosterone cypionate) and the medication darolutamide. The trial aims to assess the safety and effectiveness of this alternating treatment and its impact on quality of life and biological changes in the body. Men with prostate cancer that has spread and have not received hormone therapy for this condition might be suitable candidates. Participants will help researchers understand how this treatment strategy affects cancer progression and overall well-being. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on Warfarin or Coumadin unless you switch to another anticoagulant. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that darolutamide is quite safe for patients. Most side effects were mild or moderate and similar to those experienced with a placebo (a pill with no active ingredients). Only a small number of patients needed to lower their dose due to side effects.

Research suggests that testosterone cypionate is generally safe, even for men who have had prostate cancer. No significant difference in prostate cancer cases appeared between those on testosterone therapy and those who weren't. Some studies even suggest it might lower the risk of aggressive prostate cancer.

Both treatments have been well-tolerated in earlier research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a fresh approach to prostate cancer therapy by combining testosterone with darolutamide. Unlike the standard treatment options, which often focus solely on reducing androgen levels, this approach incorporates Bipolar Androgen-based Therapy (BAT). BAT involves alternating cycles of high-dose testosterone, which can potentially shock cancer cells and delay progression. Additionally, darolutamide is a newer androgen receptor inhibitor that aims to block cancer cell growth more effectively, potentially offering a more targeted and dynamic treatment strategy for patients who have not responded well to conventional hormone therapies.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research shows that darolutamide, one of the treatments in this trial, effectively blocks certain hormones linked to prostate cancer. It has been proven to extend the lives of patients with metastatic prostate cancer. In this trial, some participants will receive darolutamide combined with hormone therapy that lowers testosterone, known as androgen deprivation therapy (ADT). This combination can reduce the risk of cancer progression or death by 46% compared to a placebo.

Another group in this trial will receive testosterone therapy. Studies have found that testosterone therapy does not increase the risk of requiring additional prostate cancer treatment or dying from it. In some cases, testosterone use was associated with a 16% lower risk of developing prostate cancer. These treatments work differently to combat cancer, potentially offering benefits in managing prostate cancer. ^{1 4 6 7 8}

Who Is on the Research Team?

Samuel Denmeade, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Men with metastatic prostate cancer who haven't had hormonal therapy yet can join this trial. It's not for those who've already received certain treatments or have specific health conditions that the study doesn't list.

Inclusion Criteria

Baseline PSA ≥1.0 ng/ml

My prostate cancer was confirmed through a tissue examination.

Evidence of rising PSA on two successive dates > 2 weeks apart

Exclusion Criteria

I have a condition that could worsen with testosterone therapy.

Evidence of serious and/or unstable pre-existing medical, psychiatric or other condition that could interfere with patient safety or provision of informed consent

I am not on Warfarin or Coumadin blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-In Phase

Participants initiate combined androgen deprivation therapy (ADT) with an LHRH agonist or antagonist in combination with darolutamide for 6 months

6 months

Regular visits as per protocol

Darolutamide Cycle

Participants proceed to a cycle off BAT and start darolutamide alone at 600 mg twice daily for 12 weeks

12 weeks

Regular visits as per protocol

Bipolar Androgen-based Therapy (BAT) Cycle

Participants receive intermittent intramuscular testosterone cypionate at a dose of 400 mg every 4 weeks for a total of 3 injections

12 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Darolutamide
• Testosterone cypionate

Trial Overview The trial tests if high doses of testosterone followed by darolutamide, a prostate cancer drug, is safe and effective as a first-line treatment. Participants will also receive an LHRH analogue to manage hormone levels.

How Is the Trial Designed?

Group I: Lead-In Phase - ADT with an LHRH agonist or antagonist Experimental Treatment 2 Interventions

Eligible patients will initiate combined androgen deprivation therapy (ADT) with an LHRH agonist or antagonist (e.g. Eligard, Zoladex, Lupron, Orgovyx) in combination with standard dose darolutamide (600 mg twice daily) for a total of 6 months. After this initial "lead-in" phase, patients who have clinical or radiographic progression or do not have at least a ≥50% decline in PSA will remain on combined androgen deprivation and discontinue study.

Group II: Darolutamide Cycle Experimental Treatment 1 Intervention

Patient will proceed to a cycle off BAT and start darolutamide alone at 600 mg twice daily for 12 weeks. Patients will continue with alternating cycles of BAT or darolutamide (without ADT) until clinical or radiographic progression.

Group III: Bipolar Androgen-based Therapy (BAT) Cycle Experimental Treatment 1 Intervention

Patients with ≥50% decline in PSA will discontinue combined androgen deprivation and will receive intermittent intramuscular testosterone cypionate (T) at a dose of 400 mg every 4 weeks for a total of 3 injections while on a BAT cycle (12 weeks).

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e17108

Real world outcomes of darolutamide efficacy and safety in ... Adverse events led to dose reductions in 4.5% (n=6) of nmHSPC and 1.8% (n=1) of mHSPC patients. Surgical data for 51.1% (n=68) of nmHSPC ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12589698/

Assessing the efficacy of darolutamide in metastatic hormone ... The primary outcome was overall survival (OS), while the secondary outcomes included risk to castration-resistant prostate cancer (CRPC) and ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2119115

Darolutamide and Survival in Metastatic, Hormone ... Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration- ...

4. nature.com nature.com/articles/s41391-025-01047-7

DARolutamide ObservationaL (DAROL) study in patients ... Darolutamide showed consistent safety and effectiveness in DAROL vs ARAMIS. Most treatment-emergent adverse events were grade 1/2. Two-year ...

5. onclive.com onclive.com/view/darolutamide-plus-adt-is-efficacious-in-mhspc-regardless-of-disease-volume

Darolutamide Plus ADT Is Efficacious in mHSPC ... Darolutamide plus ADT improved rPFS in mHSPC patients, reducing progression or death risk by 46% compared to placebo plus ADT. · High-volume ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37660438/

Efficacy and safety outcomes of darolutamide in patients ... Darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable ...

7. urotoday.com urotoday.com/conference-highlights/esmo-2025/esmo-2025-prostate-cancer/164045-esmo-2025-darolutamide-efficacy-quality-of-life-and-safety-outcomes-by-age-subgroup-aranote-post-hoc-analyses.html

ESMO 2025: Darolutamide Efficacy, Quality of Life, and ... In patients with mHSPC, darolutamide consistently showed high efficacy, a similar incidence of treatment emergent adverse events to placebo, with similar or ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S258893112500255X

A Subgroup Analysis of the Phase 3 ARASENS Trial In the 219 patients aged ≥75 yr in ARASENS, darolutamide demonstrated improved efficacy versus placebo and favorable safety, consistent with the ...