Testosterone + Enzalutamide for Prostate Cancer

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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Previous studies of high dose testosterone therapy given intramuscularly to men with metastatic castrate resistant prostate cancer suggest that high serum levels of testosterone may be required for clinical response. This injection regimen was given as one dose of 400mg injection every 28 days, which initially produces high serum testosterone levels but these levels drop to a varying degree in some men over the 28-day cycle. In this 30 patient trial will analyze the effects of oral testosterone therapy in men with metastatic castrate resistant prostate cancer taken on a schedule of seven days of oral testosterone therapy followed by seven days of no therapy for a twenty-eight day cycle. This therapy will be given for three 28 day cycles consecutively followed by radiographic scans to evaluate the metastatic disease. Patients will be allowed to continue on this therapy until the patients show signs of radiographic progression. If the patients show signs of radiographic progression after the first three cycles, the patients will stop taking the oral testosterone therapy and begin taking enzalutamide therapy. Enzalutamide therapy will be taken for three 28 day cycles, then radiographic scans will be taken. If there are no signs of radiographic progression, patients can continue to take enzalutamide therapy for an additional 3 cycles while on study. Patients with continued PSA or objective response will come off study but continue on enzalutamide as standard of care therapy. This study will help the investigators to understand if treating these men with the highest FDA approved dose of oral testosterone therapy will achieve similar and sustained high levels of serum testosterone that will produce similar or enhanced therapeutic response to the therapy when compared to the serum testosterone levels found in the previous injection therapy trials.

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.

What data supports the effectiveness of the drug Testosterone + Enzalutamide for Prostate Cancer?

Recent studies suggest that testosterone therapy, once thought unsafe for prostate cancer patients, may improve quality of life and is being reconsidered for use in these patients. Additionally, Enzalutamide has been shown to improve survival in men with advanced prostate cancer. ^{1 2 3 4 5}

Is testosterone undecanoate safe for use in humans?

Testosterone undecanoate has been studied for safety in men with testosterone deficiency and those with prostate cancer, showing it can be used safely with individualized dosing intervals to maintain appropriate testosterone levels. ^{5 6 7 8 9}

How is the drug Testosterone Undecanoate unique in treating prostate cancer?

Testosterone Undecanoate is unique in treating prostate cancer because it represents a shift in the traditional approach, where testosterone therapy was once avoided due to concerns it might stimulate cancer growth. Recent studies suggest that testosterone therapy can improve quality of life in men with prostate cancer without increasing cancer risk, challenging previous beliefs. ^{1 2 3 10 11}

Research Team

Samuel Denmeade, MD

Principal Investigator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Testosterone Therapy in Men With Prostate Cancer. [2018]

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

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

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

Shifting the Paradigm of Testosterone Replacement Therapy in Prostate Cancer. [2020]

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

Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. [2021]

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

Initial Clinical Experience With Testosterone Undecanoate Therapy (AVEED) in Men With Testosterone Deficiency in the United States. [2018]

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

Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer. [2016]

8. England 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. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Androgen substitution with testosterone undecanoate in survivors of bilateral testicular cancer requires individually-adjusted injection intervals. [2014]

10. England pubmed.ncbi.nlm.nih.gov

Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review. [2018]

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

Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. [2021]