Testosterone Replacement for Fatigue in Male Cancer Survivors

Recruiting at 1 trial location

Overseen By Jose M Garcia, MD, PhD

Age: 18 - 65

Sex: Male

Trial Phase: Phase 2

Sponsor: Seattle Institute for Biomedical and Clinical Research

Must not be taking: Anabolic agents, Glucocorticoids

Disqualifiers: Hormone-dependent cancers, Brain cancer, others

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

Duration: 9 months

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a testosterone drug can reduce fatigue and improve the quality of life in young male cancer survivors with low testosterone levels. Participants will receive either the testosterone treatment (Testosterone Undecanoate) or a placebo for comparison. Men who have been cancer-free for at least a year, have low testosterone, and experience ongoing tiredness may be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've used anabolic agents, appetite stimulants, or systemic glucocorticoids in the past 6 months.

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

Research has shown that testosterone undecanoate is generally safe for men with low testosterone. Some studies have found a small increase in hemoglobin, a protein in red blood cells, as a potential side effect. This effect is usually mild.

The FDA has already approved testosterone undecanoate for other uses, indicating it has passed safety checks for those conditions. This approval can offer some reassurance about its safety. However, individual reactions may vary, so discussing possible side effects with a healthcare provider is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about testosterone undecanoate for treating fatigue in male cancer survivors because it directly addresses low testosterone levels, a common cause of fatigue in this group. Unlike other treatments that might target fatigue with lifestyle changes or antidepressants, testosterone undecanoate provides a hormonal boost, potentially offering more direct relief of symptoms. Its injectable form ensures consistent delivery and absorption, which can lead to more stable and predictable outcomes compared to other administration methods.

What evidence suggests that testosterone treatment might be effective for fatigue in male cancer survivors?

This trial will compare testosterone undecanoate with a placebo to assess its effects on fatigue in male cancer survivors. Studies have shown that testosterone replacement therapy can help reduce tiredness in men with low testosterone. Specifically, long-term use of testosterone undecanoate has been linked to significantly lower fatigue levels. This suggests that testosterone therapy might boost energy in male cancer survivors experiencing fatigue. However, some research indicates that testosterone therapy doesn't always improve quality of life or reduce tiredness for all cancer patients. These mixed results are important to consider when deciding to join the trial. ^{1 2 4 6 7}

Who Is on the Research Team?

Jose M Garcia, MD

Principal Investigator

VA Puget Sound Health Care System

Are You a Good Fit for This Trial?

This trial is for male cancer survivors aged 18-50 who are in remission for at least a year, experiencing fatigue, and have low testosterone levels. They must be able to consent and not have hormone-dependent cancers. Men with total testosterone below 348 ng/dL or free testosterone under 70 pg/mL may join if they haven't used appetite stimulants in the last six months.

Inclusion Criteria

I haven't used appetite stimulants in the last 6 months.

I often feel very tired and my fatigue is severe based on a specific test score.

My cancer is not driven by hormones.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive testosterone replacement therapy or placebo for 9 months

9 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Testosterone Undecanoate

Trial Overview The study tests whether Depo-Testosterone (testosterone cypionate) can improve fatigue, sexual function, life quality, body composition, muscle strength, and physical activity compared to a placebo in young male cancer survivors with low testosterone.

How Is the Trial Designed?

Group I: Testosterone Experimental Treatment 1 Intervention

Testosterone undecanoate injection 750 MG/3 ML

Group II: Placebo Placebo Group 1 Intervention

clinical grade saline 0.9% sodium chloride injection

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?

Seattle Institute for Biomedical and Clinical Research

Lead Sponsor

Trials

55

Recruited

13,700+

Published Research Related to This Trial

In a study of 54 testicular cancer survivors conducted 12 months post-treatment, 33% were found to have biochemical hypogonadism, indicating a significant prevalence of testosterone deficiency in this population.

Despite the high rates of testosterone deficiency, the study found no significant link between testosterone levels and quality of life, suggesting that low testosterone may not directly impact overall well-being in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone deficiency and quality of life in Australasian testicular cancer survivors: a prospective cohort study. O'Carrigan, B., Fournier, M., Olver, IN., et al.[2014]

Testosterone replacement therapy (TRT) may be safe for men with confirmed androgen deficiency who have either been treated for prostate cancer or have no history of the disease, according to emerging evidence.

However, there is a significant lack of high-quality evidence (level 1 studies) to fully support TRT in men with untreated prostate cancer, leading to potential safety concerns for this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of testosterone replacement therapy on the prostate: a clinical perspective. Miah, S., Tharakan, T., Gallagher, KA., et al.[2021]

In a study of 176 young male cancer survivors, 13.6% were found to have significantly low total testosterone levels, which were associated with increased fat mass and higher insulin levels compared to 213 healthy controls.

The findings suggest that testosterone replacement therapy could potentially improve body composition, sexual function, and overall quality of life in these cancer survivors, highlighting the need for further interventional studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence and consequences of androgen deficiency in young male cancer survivors in a controlled cross-sectional study. Greenfield, DM., Walters, SJ., Coleman, RE., et al.[2013]

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]

In a 6-month double-blind trial involving 136 young male cancer survivors with low-normal testosterone levels, testosterone replacement therapy significantly reduced trunk fat mass by 0.9 kg and whole-body fat mass by 1.8 kg, while increasing lean body mass by 1.5 kg.

Despite improvements in body composition, testosterone treatment did not show any significant effects on quality of life scores, indicating that while physical changes occurred, they did not translate into perceived improvements in overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone replacement in young male cancer survivors: A 6-month double-blind randomised placebo-controlled trial. Walsh, JS., Marshall, H., Smith, IL., et al.[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 involving 24 cancer patients, testosterone therapy did not significantly reduce cancer-related fatigue (CRF) symptoms or improve inflammatory markers compared to placebo.

Despite previous findings that testosterone preserved lean body mass, this treatment did not enhance health-related quality of life or functional performance in late-stage cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Adjunct Testosterone on Cancer-Related Fatigue: An Ancillary Analysis from a Controlled Randomized Trial. McGovern, KA., Durham, WJ., Wright, TJ., et al.[2023]

In a randomized, double-blind, placebo-controlled trial involving 29 hypogonadal males with advanced cancer, testosterone replacement did not show a significant improvement in fatigue scores after 29 days, indicating limited immediate efficacy for this symptom.

However, by day 72, testosterone treatment was associated with significant improvements in sexual desire and performance status, suggesting potential longer-term benefits that warrant further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial. Del Fabbro, E., Garcia, JM., Dev, R., et al.[2021]

Nebido (undecanoate) significantly improves libido and erectile function in men with hypogonadism, as well as alleviating symptoms of chronic pelvic pain and reducing body fat in those with metabolic syndrome, based on studies involving 20 to 170 participants.

While Nebido is generally safe, it can cause a clinically significant rise in PSA levels in some patients, necessitating careful monitoring and potential discontinuation of treatment, especially in reproductively active men due to its suppression of spermatogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nebido in the treatment of hypogonadism syndrome and its complications in men]. Dedov, II., Kurbatov, DG., Rozhivanov, RV., et al.[2017]

In a study of seven men who underwent orchidectomy for testicular cancer, intramuscular testosterone injections led to a significant drop in plasma testosterone levels, with levels falling below the normal range before the next injection.

Despite fluctuations in testosterone levels, sexual functioning was not directly affected; however, some patients reported psychological and physical side effects, such as loss of libido and mood changes, particularly towards the end of the injection interval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sexual functioning in testosterone-supplemented patients treated for bilateral testicular cancer. van Basten, JP., van Driel, MF., Jonker-Pool, G., et al.[2019]

Young male cancer survivors report significantly lower quality of life, energy levels, and sexual functioning compared to healthy controls, with these impairments being more pronounced in those with androgen deficiency (low testosterone levels).

Despite the observed impairments, psychological distress and self-esteem levels were normal among cancer survivors, indicating that the relationship between testosterone levels and quality of life is complex and may require further investigation through interventional trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life, self-esteem, fatigue, and sexual function in young men after cancer: a controlled cross-sectional study. Greenfield, DM., Walters, SJ., Coleman, RE., et al.[2010]

Testosterone undecanoate (TU) is a long-acting injectable testosterone replacement therapy that can be administered only four times a year, providing stable testosterone levels with an excellent safety profile.

Long-term studies, including data from patients treated for over 8 years, show that TU is effective and safe, with no serious side effects reported, making it a desirable option for hypogonadal men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testosterone undecanoate in the treatment of male hypogonadism. Edelstein, D., Basaria, S.[2014]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04049331?term=AREA%5BInterventionSearch%5D(AVEED)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=3

Testosterone Replacement in Male Cancer Survivors With ... Types of outcome measures include primary outcome measure and secondary outcome measure. ... A type of intervention model describing a clinical trial in which two ...

2. withpower.com withpower.com/trial/phase-3-hypogonadism-2-2021-5d2d4

Testosterone Replacement for Fatigue in Male Cancer ... However, a specific study found that testosterone therapy did not significantly reduce cancer-related fatigue or improve quality of life in late-stage cancer ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3424192/

Hypogonadism in male cancer patients - PMC - PubMed Central The result of this single center study showed that survival of male patients with total testosterone levels <185 ng/dl was decreased compared to patients with ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04049331/testosterone-replacement-in-male-cancer-survivors-with-fatigue-and-low-testosterone

Testosterone Replacement in Male Cancer Survivors with ... This study is to evaluate the effect of a testosterone drug called Depo-Testosterone (or 'testosterone cypionate'), an FDA-approved drug for improving fatigue.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8823386/

Long-term testosterone replacement therapy reduces ... TRT for >1 year was associated with significantly lower fatigue scores. No differences were observed regarding CIMT, CAD and cardiovascular risk.

6. uptodate.com uptodate.com/contents/cancer-related-fatigue-treatment/abstract/169

Medline ® Abstract for Reference 169 of 'Cancer-related fatigue CONCLUSION Male patients with metastatic RCC and hypogonadism receiving testosterone had less fatigue and better symptom control during targeted therapy. AD ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9771994/

Testosterone replacement in prostate cancer survivors with ... We describe the design of the first randomized trial to determine the safety and efficacy of testosterone treatment in men who have undergone prostatectomy.