Testosterone + Enzalutamide for Prostate Cancer

No longer recruiting at 1 trial location

Overseen By Rana Sullivan, RN

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must be taking: Castrating therapy

Must not be taking: Warfarin, Rivaroxaban, Apixaban

Disqualifiers: Opioid use, Prior mCRPC treatment, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating prostate cancer that has spread and does not respond to standard hormone treatments. Researchers aim to determine if high doses of oral testosterone (specifically, Testosterone Undecanoate) taken on a specific schedule can help manage the disease. If the cancer progresses, participants will switch to another medication, enzalutamide. Men may qualify for this trial if they have prostate cancer that has spread, are currently on hormone treatment, and have experienced rising PSA levels in recent tests. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking anti-androgen or abiraterone at least 4 weeks before starting the oral testosterone therapy. If you are on prednisone with abiraterone, you should try to wean off prednisone before starting the trial. If you are on Coumadin, you must switch to an alternative anticoagulation medication.

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

Research has shown that testosterone therapy is usually well-tolerated. In one study, 94% of men achieved normal testosterone levels after three injections of testosterone undecanoate, without major problems. However, some risks exist, such as increased PSA levels (which can signal prostate issues) and a higher chance of high blood pressure. Importantly, these studies did not link any new cases of prostate cancer to testosterone use.

For enzalutamide, research has found it to be effective and generally safe. One study showed that enzalutamide lowered the risk of death by 33% in prostate cancer patients compared to those who didn't take it. While some side effects occurred, the study did not find any unusual or severe safety concerns.

Both treatments have been studied for their safety and effectiveness, but discussing any concerns with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Testosterone Undecanoate and Enzalutamide for prostate cancer because this combination offers a fresh approach to treatment. Unlike the standard hormone therapy options, which typically lower testosterone levels to slow cancer growth, this strategy initially uses oral testosterone to disrupt cancer cell adaptation, followed by Enzalutamide to block androgen receptors effectively. This dual-phase approach could potentially overcome resistance to current therapies and offer a new avenue for managing advanced prostate cancer, providing hope for better outcomes.

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

This trial will explore oral testosterone therapy followed by enzalutamide therapy for prostate cancer. Research has shown that testosterone therapy can raise testosterone levels in men with low testosterone. Previous studies found that testosterone undecanoate effectively stabilizes testosterone levels, which might aid in treating prostate cancer. Although direct evidence on oral testosterone for advanced prostate cancer resistant to other treatments is limited, the aim is to achieve similar or better results compared to injections.

Participants will initially receive oral testosterone therapy until radiographic progression. After a washout period, they will receive enzalutamide therapy. Enzalutamide is well-supported as an effective treatment for prostate cancer. Studies have shown that it can significantly lower the risk of cancer progression and reduce the chance of death. This information suggests that both treatments have potential, with enzalutamide having strong evidence for improving outcomes in prostate cancer patients. ^{1 2 5 6 7}

Who Is on the Research Team?

Samuel Denmeade, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Are You a Good Fit for This Trial?

This trial is for men aged 18+ with metastatic castrate resistant prostate cancer who understand the study and consent to participate. They must have a good performance status, measurable disease by CT scan, be on castrating therapy, and show progression despite current treatments. Exclusions include use of certain anticoagulants, uncontrolled health conditions like heart failure or infections (HIV/AIDS), prior treatments for metastatic cancer, or risks from testosterone therapy due to disease location.

Inclusion Criteria

My cancer is getting worse despite hormone therapy.

I have received docetaxel treatment for prostate cancer.

My cancer has spread and can be measured on a CT scan.

Exclusion Criteria

I do not have an active, uncontrolled infection like HIV/AIDS or chronic hepatitis.

I need a catheter to urinate because of a blockage.

I had a blood clot in the last 2 years and am not on blood thinners.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Oral Testosterone Therapy

Participants receive oral testosterone therapy for three 28-day cycles, with 7 days on therapy followed by 7 days off therapy, until radiographic progression.

12 weeks

Regular visits for monitoring and radiographic scans

Enzalutamide Therapy

Participants begin enzalutamide therapy for up to six 28-day cycles if radiographic progression is observed after oral testosterone therapy.

24 weeks

Regular visits for monitoring and radiographic scans

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• Testosterone Undecanoate

Trial Overview The trial tests if high doses of oral testosterone undecanoate can maintain serum testosterone levels in these patients over a cycle of seven days on treatment followed by seven off. After three cycles and radiographic scans showing progression, patients switch to enzalutamide for another three cycles with potential continuation based on response.

How Is the Trial Designed?

Group I: Oral Testosterone Therapy given until radiographic progression followed by Enzalutamide Therapy Experimental Treatment 2 Interventions

Oral Testosterone Therapy-396 mg given twice per day on days 1-7 and 15-21 of a 28 day cycle until radiographic progression. After a 21 day washout period, Enzalutamide therapy given at 160 mg once daily will be taken for a maximum of 6 cycles while on study.

Testosterone Undecanoate is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Testosterone Undecanoate for:

• Hypogonadism
• Male hormone replacement therapy

Approved in United States as Aveed for:

• Hypogonadism
• Male hormone replacement therapy

Approved in Canada as Nebido for:

• Hypogonadism
• Male hormone replacement therapy

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Allegheny Health Network

Collaborator

Trials

6

Recruited

1,100+

Allegheny Health Network

Collaborator

Trials

7

Recruited

1,700+

Clarus Therapeutics, Inc.

Industry Sponsor

Trials

14

Recruited

1,100+

Clarus Therapeutics

Collaborator

Trials

3

Recruited

90+

Published Research Related to This Trial

In a study of 98 hypogonadal men with prostate cancer treated with radiation therapy, testosterone therapy led to a significant increase in serum testosterone levels, from a median of 209 ng/dl to 420 ng/dl, indicating effective treatment.

The therapy was associated with only a minor increase in prostate specific antigen (PSA) levels and a low rate of biochemical recurrence (6.1%), suggesting that testosterone therapy may be safe for men post-radiation treatment for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer. Pastuszak, AW., Khanna, A., Badhiwala, N., et al.[2016]

Injectable testosterone undecanoate (Nebido) effectively maintains stable testosterone levels in hypogonadal patients, requiring only 4-5 injections per year compared to 16 for conventional testosterone treatments, making it a more convenient option.

In hypogonadal patients with erectile dysfunction, 58% showed improvement with testosterone undecanoate, particularly benefiting diabetic patients, indicating its efficacy in this specific population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with the new long-acting injectable testosterone undecanoate. Report on the educational symposium on the occasion of the 5th World Congress on the Aging Male, 9-12 February 2006, Salzburg, Austria. Morales, A., Nieschlag, E., Schubert, M., et al.[2018]

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 undecanoate (TU) is safe and effective for treating patients with bilateral germ cell testicular cancer (GCTC) who require androgen substitution, as shown in a study of 47 patients over 28 weeks.

The study found that while testosterone levels varied significantly during treatment, most patients could maintain effective hormone levels with individually adjusted injection intervals, typically around 10 weeks, without severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen substitution with testosterone undecanoate in survivors of bilateral testicular cancer requires individually-adjusted injection intervals. Brabrand, S., Fosså, SD., Cvancarova, M., et al.[2014]

In a phase 3 trial involving 1125 men with metastatic, hormone-sensitive prostate cancer, adding enzalutamide to testosterone suppression significantly improved overall survival, with a 3-year survival rate of 80% compared to 72% in the standard-care group.

While enzalutamide showed better progression-free survival and overall survival, it was associated with a higher incidence of adverse effects, including fatigue and seizures, particularly in patients also receiving early docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. Davis, ID., Martin, AJ., Stockler, MR., et al.[2021]

Recent studies suggest that testosterone replacement therapy (TRT) may improve the quality of life for men with hypogonadism, even those with a history of prostate cancer, challenging the traditional view that TRT should be avoided in these patients.

There is a growing acceptance among some healthcare providers for the use of TRT in men who have been treated for prostate cancer or are under active surveillance, although clinical guidelines on this topic remain inconsistent and further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shifting the Paradigm of Testosterone Replacement Therapy in Prostate Cancer. Bell, MA., Campbell, JD., Joice, G., et al.[2020]

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]

In a study of 147 men with testosterone deficiency, testosterone undecanoate (TU 750 mg) significantly increased total and free testosterone levels, leading to symptomatic improvement in 66% of patients.

The treatment had a favorable safety profile, with only 2% of patients experiencing transient cough and no serious adverse events like strokes or new cases of prostate cancer reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Initial Clinical Experience With Testosterone Undecanoate Therapy (AVEED) in Men With Testosterone Deficiency in the United States. Krakowsky, Y., Conners, W., Davidson, E., et al.[2018]

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]

A systematic review of 44 studies involving testosterone therapy for hypogonadism found no evidence that testosterone treatment increases the risk of prostate cancer or worsens existing cancer in men.

The review included various study types, including placebo-controlled trials and studies of men with and without a history of prostate cancer, and showed that testosterone therapy did not consistently affect prostate-specific antigen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review. Shabsigh, R., Crawford, ED., Nehra, A., et al.[2018]

Testosterone replacement therapy in hypogonadal men with prostate cancer after radical prostatectomy was found to be effective, leading to significant increases in testosterone levels without increasing cancer recurrence rates, even in high-risk patients.

While there was an increase in prostate-specific antigen (PSA) levels following testosterone therapy, this did not correlate with higher rates of cancer recurrence compared to a reference group, suggesting that testosterone therapy can be safely monitored in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. Pastuszak, AW., Pearlman, AM., Lai, WS., et al.[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. nejm.org nejm.org/doi/full/10.1056/NEJMoa2510310?query=featured_home

Improved Survival with Enzalutamide in Biochemically ... In this trial, enzalutamide plus leuprolide led to significantly longer overall survival than leuprolide alone among patients with castration- ...

3. 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 ...

4. 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 ...

5. 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 ...

6. 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 ...

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

Comparative effectiveness and safety of enzalutamide ... Effectiveness outcomes included all-cause death, prostate cancer-related death, and treatment failure. Safety outcomes included major adverse CV ...