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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-labeled, single-arm, interventional pilot study. It is being done to determine the feasibility of the administration of transdermal testosterone alternating with enzalutamide, as well as the safety and efficacy.

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.

What data supports the effectiveness of the treatment Enzalutamide, Xtandi, and Transdermal Testosterone for prostate cancer?

Recent studies suggest that testosterone therapy, once thought to be unsafe for men with prostate cancer, is now considered a viable option for treating testosterone deficiency in these patients. This shift is based on evidence showing that testosterone therapy can be safe and beneficial, improving well-being and physical strength, although careful monitoring is necessary to ensure prostate safety. ^{1 2 3 4 5}

Is testosterone therapy safe for people with prostate cancer?

Testosterone therapy has been studied for safety in men with prostate cancer, and while short-term use appears safe, there are concerns about long-term risks, especially regarding prostate health. More large, long-term studies are needed to fully understand the safety of testosterone therapy in this group. ^{5 6 7 8 9}

How does the treatment Transdermal Testosterone differ from other treatments for prostate cancer?

Transdermal Testosterone is unique because it challenges the traditional belief that testosterone therapy is unsafe for men with prostate cancer. Recent studies suggest that it can be safely used in men with prostate cancer, potentially improving their quality of life by addressing symptoms of low testosterone (hypogonadism) without significantly increasing cancer risk. ^{1 2 8 10 11}

Research Team

Laura Graham

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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 (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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Testosterone Therapy on Active Surveillance and Following Definitive Treatment for Prostate Cancer. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Testosterone Therapy in Men With Prostate Cancer. [2018]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Association between Basal Total Testosterone Levels and Tumor Upgrading in Low and Intermediate Risk Prostate Cancer. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The current status of therapy for symptomatic late-onset hypogonadism with transdermal testosterone gel. [2013]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Testosterone Replacement Therapy in Men with Untreated or Treated Prostate Cancer: Do We Have Enough Evidences? [2021]

6. England pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Testosterone therapy does not increase the risks of prostate cancer recurrence or death after definitive treatment for localized disease. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

The Role of Testosterone Therapy in the Setting of Prostate Cancer. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

The relationship between total testosterone levels and prostate cancer: a review of the continuing controversy. [2022]

10. Netherlands pubmed.ncbi.nlm.nih.gov

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

11. Netherlands pubmed.ncbi.nlm.nih.gov

Testosterone Therapy After Prostate Cancer Treatment: A Review of Literature. [2021]