Testosterone Replacement Therapy for Prostate Cancer

No longer recruiting at 3 trial locations

Overseen By Arthur Burnett, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Testosterone, Estrogens, Antiandrogens, others

Disqualifiers: Radiation therapy, Severe sleep apnea, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether testosterone replacement therapy (TRT) can improve symptoms such as low energy and sexual dysfunction in men who have undergone prostate removal surgery for prostate cancer. The study compares a weekly testosterone injection (Testosterone Cypionate) to a placebo to assess improvements in symptoms and quality of life. Suitable participants have had prostate cancer confined to the gland, have not undergone radiation therapy, and experience symptoms like fatigue or sexual dysfunction. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to important findings.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications. However, you cannot participate if you've used testosterone, DHEA, estrogens, GnRH analogs, antiandrogens, spironolactone, ketoconazole, rhGH, megestrol acetate, or prednisone 20 mg daily (or equivalent glucocorticoids) in the past 6 months.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot participate if you've used certain medications like testosterone, DHEA, or estrogens in the past 6 months. It's best to discuss your current medications with the trial team.

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

Research has shown that testosterone replacement therapy (TRT) does not directly increase the risk of prostate cancer. One study found that men using testosterone had a prostate cancer rate of 9.2 cases per 1,000 person-years, while those not using testosterone had a rate of 8.3 cases, indicating similar risk levels for both groups.

Testosterone cypionate, a type of TRT, can cause side effects such as increased red blood cells, breast tissue growth, headaches, and mood changes like depression. Older adults may be more susceptible to these effects.

The study is in its second phase, indicating it has already undergone initial human testing. This phase focuses more on the drug's effectiveness, while safety remains a priority. Reaching this phase suggests that early results demonstrated sufficient safety to proceed. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about testosterone cypionate for prostate cancer because it takes a different approach compared to traditional treatments like hormone therapy or chemotherapy. Unlike these treatments, which often aim to lower testosterone levels to slow cancer growth, this therapy introduces testosterone cypionate, a synthetic form of testosterone, to potentially disrupt the cancer's ability to adapt and resist treatment. This novel approach could offer a fresh angle in managing prostate cancer, especially for cases that become resistant to conventional therapies. Additionally, the weekly intramuscular administration offers a consistent dosing schedule, which might be more convenient for some patients.

What evidence suggests that testosterone replacement therapy could be effective for prostate cancer?

This trial will compare testosterone replacement therapy (TRT) with a placebo to assess its effects on men with prostate cancer who have low testosterone levels. Research has shown that TRT can improve quality of life, enhancing sexual health, physical energy, and mood. One study found that TRT did not increase the risk of prostate cancer in patients, suggesting it might be safe for those already treated for it. However, the overall effect on cancer progression remains under study, with some research indicating benefits for certain patients. While TRT is still under investigation, early findings are promising for improving symptoms related to low male hormone levels. ^{1 3 4 6 7}

Who Is on the Research Team?

Shalender Bhasin, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for men over 40 with prostate cancer who've had a radical prostatectomy, have low testosterone levels, and symptoms like sexual dysfunction or fatigue. They must have stable PSA levels post-surgery and not be on certain medications or treatments related to hormones, heart failure, severe sleep apnea, or psychiatric disorders.

Inclusion Criteria

I am a man with early-stage prostate cancer, low Gleason score, low PSA before surgery, and stable PSA for 2 years post-surgery.

Ability and willingness to provide informed consent

My morning testosterone levels are low.

Exclusion Criteria

I have recently taken certain medications.

BMI >40 kg/m2

I am a man diagnosed with a major psychiatric disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly IM administration of 100 mg testosterone cypionate or placebo for 12 weeks

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of PSA recurrence and changes in various health metrics

5-8 months

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Testosterone Cypionate

Trial Overview The study tests if Testosterone Cypionate improves quality of life in prostate cancer survivors with androgen deficiency compared to a placebo. It's a phase II trial focusing on safety and how effective the treatment is at alleviating symptoms associated with low testosterone after surgery.

How Is the Trial Designed?

Group I: Treatment Arm Active Control 1 Intervention

Weekly IM administration of 100 mg testosterone cypionate for 12 weeks.

Group II: Control Arm Placebo Group 1 Intervention

Weekly IM administration of placebo for 12 weeks.

Testosterone Cypionate is already approved in United States for the following indications:

Approved in United States as Depo-Testosterone for:

• Primary hypogonadism
• Hypogonadotropic hypogonadism
• Delayed puberty

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

In a study of 126 prostate cancer patients undergoing LHRH agonist treatment, free testosterone levels at 6 months were found to be a better predictor of survival free of castration resistance compared to total testosterone, especially in patients without metastasis.

The research identified that a free testosterone threshold of 1.7 pg/ml significantly correlated with better outcomes, suggesting that monitoring free testosterone could improve treatment strategies for non-metastatic prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Free Testosterone During Androgen Deprivation Therapy Predicts Castration-Resistant Progression Better Than Total Testosterone. Regis, L., Planas, J., Carles, J., et al.[2018]

Androgen therapy is primarily used for treating symptomatic hypogonadal men, but it is also being explored for other uses such as treating age-related testosterone decline in older men, muscle-wasting diseases, and as a potential male contraceptive.

New formulations of androgen therapy, including long-acting injectables and transdermal systems, are being developed, but the benefits must be carefully balanced against risks, especially when used for conditions beyond male hypogonadism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen replacement therapy. Wang, C., Swerdloff, RS.[2019]

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 794 men from the Baltimore Longitudinal Study of Aging, higher levels of calculated free testosterone were linked to an increased risk of prostate cancer, particularly in older men.

Men with lower free testosterone index (hypogonadal FTI) had a decreased risk of prostate cancer, suggesting that testosterone therapy should be carefully monitored for potential cancer risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serum testosterone and the risk of prostate cancer: potential implications for testosterone therapy. Parsons, JK., Carter, HB., Platz, EA., et al.[2013]

Testosterone substitution treatment is essential for individuals with irreversible conditions that lower testosterone levels, requiring almost life-long therapy to maintain normal physiological levels.

Long-acting testosterone preparations, such as implants and injectable testosterone undecanoate, are effective options, providing stable testosterone levels for 3-6 months and 12 weeks, respectively, with minimal side effects in younger patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New long-acting androgens. Gooren, LJ.[2018]

Testosterone substitution therapy can be safely administered to men with late onset hypogonadism (LOH) who have a history of cured prostate cancer, without increasing the risk of cancer relapse, based on limited data from small patient groups.

For men with untreated or active prostate cancer, the decision to proceed with testosterone replacement therapy must be carefully considered on a case-by-case basis, weighing the potential benefits against the risks of disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Testosterone substitution therapy in prostate cancer]. Kaminsky, A., Sperling, H.[2021]

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]

Testosterone levels naturally decline in men during their 40s, and symptoms like low libido and erectile dysfunction can indicate late-onset hypogonadism (LOH), but it's crucial to rule out prostate cancer before starting testosterone therapy.

Limited studies suggest that testosterone replacement therapy may be safe for men with a history of cured prostate cancer, provided they are well-informed and monitored throughout the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Testosterone replacement therapy for prostate cancer]. Kaminsky, A., Sperling, H.[2021]

Prostate cancer is highly sensitive to hormones, and optimal androgen blockade, particularly through combined androgen blockade (CAB) with castration and a pure anti-androgen, has been shown to prolong life and provide long-term control or cure in over 90% of localized cases.

Recent findings indicate that even after castration, local production of testosterone from DHEA in the prostate can still occur, suggesting that further androgen blockade may be beneficial in treatment-resistant cases, highlighting the need for more effective anti-androgens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal therapy of prostate cancer. Labrie, F.[2014]

Hormonal therapy for prostate cancer primarily involves reducing testosterone levels, with diethylstilbestrol showing a survival benefit in advanced cases, while newer treatments like luteinizing hormone-releasing hormone agonists have largely replaced surgical options.

Intermittent androgen blockade may provide similar benefits to continuous androgen suppression but with fewer side effects and lower costs, highlighting the importance of personalized treatment strategies in managing prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal therapy for prostate cancer. Brawer, MK.[2023]

Testosterone replacement therapy aims to restore testosterone levels to physiological ranges, with natural testosterone being the preferred option due to its ability to convert to active forms like DHT and E2, which are important for various bodily functions.

Parenteral testosterone undecanoate is a significant advancement, maintaining normal testosterone levels for up to 12 weeks, while transdermal gels offer flexibility and fewer side effects, highlighting the importance of patient involvement in choosing the most suitable testosterone preparation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen replacement therapy: present and future. Gooren, LJ., Bunck, MC.[2022]

In a study of 234 hypogonadal men, both intramuscular testosterone cypionate (IM-TC) and subcutaneous testosterone enanthate autoinjector (SCTE-AI) significantly increased total testosterone levels, but SCTE-AI resulted in lower estradiol and hematocrit levels, suggesting a better safety profile.

SCTE-AI did not lead to significant increases in prostate-specific antigen (PSA) levels, indicating that it may be a safer option for testosterone replacement therapy compared to IM-TC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Outcomes for Hypogonadal Men Treated with Intramuscular Testosterone Cypionate versus Subcutaneous Testosterone Enanthate. Choi, EJ., Xu, P., Barham, D., et al.[2022]

The ARTFORM study is a randomized controlled trial designed to assess the effectiveness of testosterone replacement therapy in improving quality of life for male patients with advanced cancer and low testosterone levels.

The primary outcome will be measured through health-related quality of life questionnaires at week 12, providing insights into how androgen replacement may alleviate cancer-related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Androgen replacement therapy for cancer-related symptoms in male advanced cancer patients: study protocol for a randomised prospective trial (ARTFORM study). Izumi, K., Shigehara, K., Nohara, T., et al.[2018]

Testosterone replacement therapy may be a safe option for certain hypogonadal men with low-risk prostate cancer who are undergoing treatment with curative intent, as long as there is no active disease present.

Current evidence supporting this approach is limited, indicating that careful selection of patients is crucial before considering testosterone therapy in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of Hypogonadism in Low-Risk Prostate Cancer Survivors. Agrawal, L., Arceo-Mendoza, RM., Barnosky, A., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4709428/

Testosterone Replacement Therapy and Prostate Cancer ... Rhoden and Morgentaler [29] reported outcomes in 20 men with PIN on testosterone supplementation. After one year of therapy, they reported no change in PSA.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3424887/

Testosterone replacement and prostate cancer - PMC To date no study or review has documented any direct evidence that testosterone therapy increases incident prostate cancer risk. However, it is still difficult ...

3. mdpi.com mdpi.com/2075-1729/11/9/884

Titration of Androgen Signaling: How Basic Studies Have ... These trials suggest a clinical benefit in cancer response and quality of life in a subset of castration-resistant prostate cancer patients.

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/pdf/10.1111/andr.13299

Testosterone replacement in prostate cancer survivors with ... Efficacy outcomes are assessed at 6 and 12 weeks and include measures of sexual, physical, cognitive, and mood functions. Adverse event ...

5. bjui-journals.onlinelibrary.wiley.com bjui-journals.onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2011.10719.x

Testosterone in prostate cancer: the Bethesda consensus The 50 ng/dL threshold has been questioned as a result of reports indicating worse outcomes for levels between 20 and 50 ng/dL. Instead, a 20 ng ...

6. evidence.nejm.org evidence.nejm.org/doi/full/10.1056/EVIDoa2300171

Targeted Inhibition of CYP11A1 in Castration-Resistant ... All 45 patients were evaluable for safety and PSA response (Fig. S2). Of the 92 patients enrolled in the study, 14 (15.2%) died during dosing or ...

7. aetna.com aetna.com/cpb/medical/data/1000_1099/1014.html

Testosterone Cypionate Injections - Medical Clinical Policy ... Other adverse reactions include polycythemia, gynecomastia, headache, and depression. Geriatric patients treated with androgens may also be at risk for ...