NCT07142551

Supraphysiologic Testosterone Priming Induces Darolutamide Extended Response

Supraphysiologic Testosterone Priming Induces Darolutamide Extended Response Via Modulation of ANdrogen Receptor (the SPIDERMAN Trial)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The objective of this study is to determine the safety and clinical effects of alternating pharmacologic (i.e. supraphysiologic) testosterone therapy with darolutamide in men with metastatic prostate cancer as first line hormonal therapy. Correlative studies will be conducted to assess the effect of alternating therapy on quality of life, gene expression and metabolic changes associated with alternating therapy.

Detailed description

This research is being done to determine if alternating high dose testosterone and prevent the development of resistance to hormone therapy. It is also being done to determine if this alternating therapy can decease the side effects of hormone therapy and improve the participant's quality of life. Right now, patients who develop metastatic prostate cancer are treated with medications that block testosterone effects as first-line therapy. Eventually, the testosterone blocking therapies become ineffective and the tumor begins to grow. The investigaors call this phase of the disease castrater-resistant prostate cancer (CRPC). Previous research has shown that prostate cancer cells can eventually adapt to low testosterone conditions produced by hormone therapy and begin to grow again. The investigators have learned that these resistant prostate cancer cells can killed by high levels of testosterone followed by a rapid drop to low testosterone levels. The investigators call this treatment bipolar androgen therapy (BAT) because the investigators are going from the polar extremes of high and low testosterone in the blood every 28 days. The investigators have tested this idea in previous studies by giving injections of high doses of testosterone to patients with CRPC. In these trials, the investigators saw that BAT was safe. BAT produced decreases in PSA levels and decreases in tumor size in some patients. After treatment with BAT, many patients had an improved response to the testosterone-blocking drug enzalutamide. The drug used in this study, darolutamide, is similar to enzalutamide. Both drugs are considered to be antiandrogens that block effects of testosterone within the prostate cancer cells. The investigators also did a study called the BATMAN study in patients with mHSPC. These patients received alternating therapy with high dose testosterone and ADT as first line therapy. In this study, alternating testosterone and ADT was found to be safe. In this study, more patients remained sensitive to hormone therapy after 18 months than the investigators would have expected with ADT alone. In this study, the investigators would like to see if improvement on these results and decrease hormonal side effects when the investigators give testosterone in sequence with darolutamide.

Conditions

• Metastatic Castration-resistant Prostate Cancer

Interventions

Type	Name	Description
DRUG	Testosterone cypionate	Intermittent intramuscular testosterone cypionate (T) at a dose of 400 mg every 4 weeks.
DRUG	Luteinizing hormone-releasing hormone (LHRH) analogue	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.
DRUG	Darolutamide	600 mg twice daily during the lead-in phase and on darolutamide cycle.

Timeline

• Start date: 2026-03-09
• Primary completion: 2030-06-01
• Completion: 2034-06-01
• First posted: 2025-08-26
• Last updated: 2026-03-11

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study