Testosterone Therapy for Prostate Cancer

Overseen By Michael D Wacker

Age: 18+

Sex: Male

Trial Phase: Phase < 1

Sponsor: University of Colorado, Denver

Must be taking: GnRH analogue

Must not be taking: Second-generation anti-androgens

Disqualifiers: Cardiovascular disease, Seizure history, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the use of a combination of transdermal testosterone (a hormone therapy applied to the skin) and enzalutamide (also known as Xtandi, a medication for prostate cancer) to treat prostate cancer. Researchers aim to determine if this method is both safe and effective for patients. The trial seeks men with prostate cancer who are currently undergoing hormone therapy (a treatment to lower or stop testosterone production). Participants should not experience severe pain or require daily narcotic medication for cancer-related pain. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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

If you are on a first-generation anti-androgen medication, you must stop taking it at least 6 weeks before starting the trial. The protocol does not specify other medication restrictions, so it's best to discuss your current medications with the study team.

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

Research has shown that transdermal testosterone is usually well-tolerated. Studies found no significant increase in serious prostate cancer cases among men using testosterone therapy compared to those not using it. Specifically, one study found that only 0.5% of men on testosterone developed prostate cancer, similar to those not on the therapy.

For enzalutamide, research indicates it effectively helps men with prostate cancer. It has been linked to a lower risk of cancer progression and improved survival rates. Most men tolerate it well, with survival rates much higher when combined with standard treatments.

Both treatments appear promising with manageable safety. However, since this trial is in an early phase, detailed safety information is still being collected. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard care for prostate cancer, which typically relies on androgen deprivation therapy (ADT) to lower testosterone levels, transdermal testosterone therapy introduces testosterone into the body through the skin. This approach is unique because it alternates with the standard enzalutamide treatment, potentially offering a new way to manage the disease by cycling between boosting and blocking testosterone. Researchers are excited about this method as it could disrupt the conventional treatment cycle and lead to improved outcomes and quality of life for patients.

What evidence suggests that this treatment might be an effective treatment for prostate cancer?

Research has shown that testosterone therapy might be safe for prostate cancer patients. Some studies found positive results with testosterone treatment after prostate cancer surgery. However, other research suggests that higher testosterone levels could increase the risk of prostate cancer. In this trial, all participants will receive transdermal testosterone therapy. Additionally, they will receive enzalutamide, which significantly slows cancer progression and improves survival rates. It reduces the risk of death and helps patients live longer without cancer spreading. These findings suggest that both treatments could benefit prostate cancer care. ^{3 5 6 7 8}

Who Is on the Research Team?

Laura Graham

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Men over 18 with advanced prostate cancer that's resistant to castration therapy can join. They must have been on hormone therapy for at least 6 months, show PSA progression despite treatment, and not be in severe pain or on daily narcotics. Participants need normal organ function tests and agree to use two forms of birth control if applicable.

Inclusion Criteria

Provision to sign and date the consent form

Progressive disease at screening as defined by one or more of the following criteria:

My prostate cancer was confirmed by a lab test.

Exclusion Criteria

I have stomach or intestine problems that could affect medicine absorption.

I have not had a heart attack in the last 6 months.

I have had a seizure before or lost consciousness/had a mini-stroke in the last year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive transdermal testosterone alternating with enzalutamide

12 months

Visits every four weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• Transdermal Testosterone

Trial Overview The study is testing the safety and effectiveness of applying testosterone through the skin alternated with a drug called Enzalutamide. It aims to see if this approach is feasible for men whose prostate cancer has stopped responding to standard hormonal treatments.

How Is the Trial Designed?

Group I: Square Wave Testosterone Therapy + SOC Experimental Treatment 2 Interventions

All patients will receive transdermal testosterone. All patients will also receive standard of care enzalutamide. Patients will alternate between the two therapies.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Cancer League of Colorado

Collaborator

Trials

13

Recruited

450+

Published Research Related to This Trial

Testosterone therapy (TTh) can significantly improve the quality of life for men, and concerns about it increasing the risk of prostate cancer or cardiovascular issues are not strongly supported by current evidence.

While the safety of TTh in men with a history of prostate cancer remains uncertain, existing data does not convincingly show that TTh causes or worsens prostate cancer, suggesting that it may be considered for treating hypogonadal men with such a history, albeit with caution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Testosterone Therapy in the Setting of Prostate Cancer. Rodriguez, KM., Pastuszak, AW., Khera, M.[2018]

In a study of 69,984 men with localized prostate cancer, testosterone therapy (TT) after treatment did not increase the risk of biochemical recurrence or mortality, indicating its safety for patients post-treatment.

Among the 469 men who received TT after surgery and 543 after radiation, there were no significant differences in cancer-specific or overall mortality compared to those who did not receive TT, suggesting that TT can be safely administered to appropriate patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease. Sarkar, RR., Patel, SH., Parsons, JK., et al.[2021]

Testosterone therapy can significantly improve well-being, muscle and bone mass, strength, and libido in men with late-onset hypogonadism, but achieving optimal therapy remains challenging due to the limitations of oral testosterone delivery.

While current evidence suggests testosterone therapy is safe, it is crucial to monitor prostate health through digital rectal exams and PSA levels, especially during the first 3-6 months of treatment, to mitigate the risk of promoting pre-existing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current status of therapy for symptomatic late-onset hypogonadism with transdermal testosterone gel. Ebert, T., Jockenhövel, F., Morales, A., et al.[2013]

Recent evidence indicates that testosterone therapy in men with prostate cancer does not increase the risk of cancer progression or aggressive disease, challenging previous beliefs about its safety.

Men undergoing testosterone therapy for localized prostate cancer showed no higher rates of recurrence or adverse clinical outcomes, suggesting that testosterone treatment may be a viable option for those with testosterone deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone Therapy on Active Surveillance and Following Definitive Treatment for Prostate Cancer. Golla, V., Kaplan, AL.[2022]

Testosterone replacement therapy (TRT) does not appear to significantly increase the risk of disease progression in men with prostate cancer compared to those not receiving TRT, based on a systematic review of 36 studies involving 2,459 patients.

However, TRT may be harmful for men with advanced prostate cancer, those undergoing active surveillance, and those with high-risk disease after treatment, indicating that caution is needed in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone Replacement Therapy in Men with Untreated or Treated Prostate Cancer: Do We Have Enough Evidences? Kim, M., Byun, SS., Hong, SK.[2021]

Recent literature indicates that testosterone therapy does not increase the risk of prostate cancer or lead to more aggressive disease in men with testosterone deficiency, challenging the long-held belief that higher testosterone levels promote cancer growth.

Men with a history of localized prostate cancer who receive testosterone therapy do not experience higher rates of cancer recurrence or worse outcomes, suggesting that testosterone therapy can be a safe and effective option for managing testosterone deficiency in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone Therapy in Men With Prostate Cancer. Kaplan, AL., Hu, JC., Morgentaler, A., et al.[2018]

Testosterone replacement therapy is increasingly prescribed for older men, but concerns exist regarding its long-term risks, particularly related to prostate health, including benign prostatic hypertrophy (BPH) and prostate cancer.

Current data suggest that short-term use of testosterone therapy is relatively safe, but the studies reviewed involved small participant numbers, highlighting the need for larger, long-term studies to fully understand the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of androgen supplementation therapy on the prostate. Kaufman, JM.[2013]

Recent evidence suggests that testosterone therapy can be safely offered to many men with prostate cancer, challenging the outdated prohibition based on concepts from over 70 years ago.

Men with prostate cancer who have symptoms of testosterone deficiency may experience significant improvements in their quality of life with testosterone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone Therapy in a Man with Intermediate-risk Prostate Cancer: Pro. Morgentaler, A.[2021]

Citations

1. pfizer.com pfizer.com/news/press-release/press-release-detail/astellas-and-pfizers-xtanditm-enzalutamide-shows-long-term

Astellas and Pfizer's XTANDI™ (enzalutamide) Shows ... OS at 96 months was 50% with XTANDI and 40% for NSAA; progression-free survival (PFS) also favored XTANDI over NSAA (HR: 0.49; 95% CI, 0.42-0.57) ...

2. xtandihcp.com xtandihcp.com/cspc/efficacy

Efficacy CSPC | HCP Site | XTANDI® (enzalutamide) XTANDI (single agent) significantly improved metastasis-free survival vs placebo + GnRH therapy* · Number of events: 63 (17.7%) with XTANDI (single agent) vs 92 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40660075/

The efficacy and safety of enzalutamide in metastatic ... Results: The data of 2275 patients were analyzed eventually. Enzalutamide reduced the risk of death by 33% compared to the control. Specifically ...

4. xtandi.com xtandi.com/clinical-trials

Clinical Trial Results | XTANDI® (enzalutamide) Men taking XTANDI had a 61% lower chance of their cancer progressing compared with men not taking XTANDI during the study. Progression was seen in 89 men (15.5 ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2003892

Enzalutamide and Survival in Nonmetastatic, Castration ... Preliminary trial results showed that enzalutamide significantly improved metastasis-free survival among men who had nonmetastatic, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12504157/

Comparative effectiveness and safety of enzalutamide ... The median overall survival of pre-docetaxel abiraterone and enzalutamide was 36.1 and 39.9 months, respectively. In contrast, the median ...

7. pfizer.com pfizer.com/news/press-release/press-release-detail/xtandir-plus-leuprolide-reduced-risk-death-40-vs-leuprolide

XTANDI® Plus Leuprolide Reduced Risk of Death by 40% ... The probability of survival at 8 years was an unprecedented 78.9% with XTANDI plus leuprolide versus 69.5% with leuprolide, in men with ...

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2833622

Enzalutamide and Prostate-Specific Antigen Levels in ... In this study, enzalutamide plus ADT was associated with improved outcomes in men with mHSPC regardless of pretreatment PSA level.