Testosterone + Enzalutamide for Prostate Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen bySamuel Denmeade, MD
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
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
Prior Safety Data
Approved in 3 Jurisdictions
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.
12345Is 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.
56789How 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.
1231011Eligibility 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.
+11 more
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.
+5 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Oral Testosterone Therapy given until radiographic progression followed by Enzalutamide TherapyExperimental Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns Hopkins HospitalBaltimore, MD
Allegheny Health NetworkPittsburgh, PA
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Who Is Running the Clinical Trial?
Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsLead Sponsor
Allegheny Health NetworkCollaborator
Allegheny Health NetworkCollaborator
Clarus Therapeutics, Inc.Industry Sponsor
Clarus TherapeuticsCollaborator
References
Testosterone Therapy in Men With Prostate Cancer. [2018]The use of testosterone therapy in men with prostate cancer was previously contraindicated, although recent data challenge this axiom. Over the past 2 decades, there has been a dramatic paradigm shift in beliefs, attitude, and treatment of testosterone deficiency in men with prostate cancer.
Testosterone Therapy on Active Surveillance and Following Definitive Treatment for Prostate Cancer. [2022]Previously considered an absolute contraindication, the use of testosterone therapy in men with prostate cancer has undergone an important paradigm shift. Recent data has changed the way we approach the treatment of testosterone deficiency in men with prostate cancer. In the current review, we summarize and analyze the literature surrounding effects of testosterone therapy on patients being treated in an active surveillance protocol as well as following definitive treatment for prostate cancer.
Shifting the Paradigm of Testosterone Replacement Therapy in Prostate Cancer. [2020]Historically, testosterone and prostate cancer have been demonstrated to have a positive association leading providers to forgo testosterone replacement therapy (TRT) in men with concurrent histories of hypogonadism and prostate cancer. This paradigm has been gradually shifting with our evolving understanding of the relationship between testosterone and prostate cancer and the gaining popularity of the saturation model. Newer data suggests improved quality of life for men with hypogonadism after TRT leading to a more tempered view of the effects of this treatment and its risk in prostate cancer. As more reports emerge of TRT in men who have either undergone definitive treatment for prostate cancer or are on active surveillance, some providers see a role for TRT in these patients despite non-consensus in clinical guidelines. It is critical that we examine evidence currently available, while we await more rigorous data to emerge.
Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. [2021]Enzalutamide, an androgen-receptor inhibitor, has been associated with improved overall survival in men with castration-resistant prostate cancer. It is not known whether adding enzalutamide to testosterone suppression, with or without early docetaxel, will improve survival in men with metastatic, hormone-sensitive prostate cancer.
Testosterone Replacement Therapy in Men with Untreated or Treated Prostate Cancer: Do We Have Enough Evidences? [2021]To investigate the oncologic safety of testosterone replacement therapy (TRT) in men with untreated or treated prostate cancer.
Initial Clinical Experience With Testosterone Undecanoate Therapy (AVEED) in Men With Testosterone Deficiency in the United States. [2018]To report our initial experiences with testosterone undecanoate (TU 750) mg (AVEED) in men with testosterone deficiency.
Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer. [2016]Limited literature exists regarding the safety of testosterone therapy in men treated for prostate cancer. We present multi-institutional data on testosterone therapy in hypogonadal men with prostate cancer treated with radiation therapy.
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]This symposium report summarizes first extensive clinical findings with injectable testosterone undecanoate (Nebido) in hypogonadal patients showing clinical symptoms of androgen deficiency with or without erectile dysfunction (ED). This new testosterone formulation (1000 mg testosterone undecanoate in 4 ml castor oil) possesses nearly ideal long-term kinetics, i.e. sustained close mimicking of eugonadal testosterone serum levels without supra- or sub-physiological serum concentrations. The generally accepted administration scheme recommends the second injection 6 weeks after the first one followed by further injections every 12 weeks. Applying this regimen, administration intervals are drastically reduced in comparison to conventional i.m. testosterone preparations (e.g. about 16 injections of testosterone enanthate vs. 4-5 injections of testosterone undecanoate per year). Depending on the testosterone serum levels, individualized therapy is possible by shortening (every 10 weeks) or prolonging (every 14 weeks) the injection intervals. In hypogonadal patients with ED 58% respond to testosterone undecanoate alone. Best results are seen in diabetic hypogonadal patients. The regimen of injectable testosterone undecanoate administration ideally fits recommendations regarding pharmacokinetics, efficacy and safety monitoring.
Androgen substitution with testosterone undecanoate in survivors of bilateral testicular cancer requires individually-adjusted injection intervals. [2014]• To explore the efficacy and safety of testosterone undecanoate (TU) (Nebido®; Bayer Schering Pharma AG, Berlin, Germany) in patients with bilateral germ cell testicular cancer (GCTC) who have switched androgen substitution from testosterone enanthate (Primoteston Depot®, Bayer Schering Pharma AG).
Testosterone therapy in hypogonadal men and potential prostate cancer risk: a systematic review. [2018]This paper provides a systematic review of the literature about prostate cancer risk associated with testosterone therapy for hypogonadism. A comprehensive search of MEDLINE, EMBASE and other resources was conducted to identify articles that highlight occurrences of prostate cancer in men receiving testosterone therapy for hypogonadism treatment. Articles that met study inclusion criteria were assessed for causality between testosterone treatment and prostate cancer, increased prostate-specific antigen or abnormal digital rectal examination findings. Of 197 articles relating to testosterone therapy, 44 met inclusion criteria: 11 placebo-controlled, randomized studies; 29 non-placebo-controlled studies of men with no prostate cancer history; and 4 studies of hypogonadal men with history of prostate cancer. Of studies that met inclusion criteria, none demonstrated that testosterone therapy for hypogonadism increased prostate cancer risk or increased Gleason grade of cancer detected in treated vs untreated men. Testosterone therapy did not have a consistent effect on prostate-specific antigen levels.
Testosterone replacement therapy in patients with prostate cancer after radical prostatectomy. [2021]Testosterone replacement therapy in men with prostate cancer is controversial, with concern that testosterone can stimulate cancer growth. We evaluated the safety and efficacy of testosterone in hypogonadal men with prostate cancer treated with radical prostatectomy.