Testosterone Gel for Cancer-Related Fatigue

(TEMEC Trial)

Recruiting at 3 trial locations

Overseen By Jose Garcia, MD, Phd

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Seattle Institute for Biomedical and Clinical Research

Must not be taking: Anabolic agents

Disqualifiers: Prostate cancer, Sleep apnea, others

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

Compensation: Varies

Number of Visits: 6

Duration: 6 months

230 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a large randomized, double-blind, placebo-controlled trial to determine the efficacy of testosterone replacement on cancer-related fatigue in older men with solid or hematologic (blood) cancer who report fatigue and have low testosterone levels.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are using anabolic agents like testosterone, DHEA, or growth hormone, you must have stopped them at least 6 months before joining the trial.

What data supports the effectiveness of the drug Testosterone Gel for Cancer-Related Fatigue?

Testosterone replacement has been shown to improve quality of life and reduce fatigue in patients with non-cancer conditions, and a study on hypogonadal males with advanced cancer suggested potential benefits for fatigue. However, a specific trial on cancer-related fatigue found that testosterone did not significantly improve fatigue symptoms or quality of life in late-stage cancer patients. ^{1 2 3 4 5}

Is testosterone gel generally safe for humans?

Testosterone gel is generally well tolerated in humans, with common side effects being mild skin reactions. However, there is a risk of unintentional transfer to others through skin contact, which can cause hormonal changes in women and children. ^{3 6 7 8 9}

How does the testosterone gel drug for cancer-related fatigue differ from other treatments?

The testosterone gel for cancer-related fatigue is unique because it uses a topical application method, allowing for easy and precise dosing, which is different from injectable or patch forms. This gel formulation is designed to restore testosterone levels to normal physiological ranges, potentially improving energy levels and quality of life in patients experiencing fatigue due to cancer. ^{3 6 7 10 11}

Eligibility Criteria

Men aged 55+ with incurable lung or colorectal cancer, experiencing fatigue and low testosterone levels after chemo/radiation therapy. They should have a life expectancy of at least 6 months, not be severely ill from other conditions, and must consent to participate.

Inclusion Criteria

I often feel very tired, more than usual.

I am a man with lung or colorectal cancer, treated with chemo or radiation, and have been NED for less than 24 months.

My testosterone levels are low, below the normal range.

Exclusion Criteria

I have a genetic condition that causes blood clots.

Body mass index (BMI) >40 kg/m2

I am not taking any glucocorticoids, except as part of chemotherapy.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline

Baseline assessments and training on gel application procedures

1 day

1 visit (in-person)

Treatment

Participants receive testosterone or placebo gel for 6 months with dose adjustment and monitoring

6 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo Gel
• Testosterone 1.62% Gel

Trial Overview The trial is testing if testosterone gel improves fatigue in older men with cancer compared to a placebo. It's randomized and double-blind, meaning neither the participants nor the researchers know who gets the real treatment until the end.

Participant Groups

Group I: testosterone 1.62% gel Experimental Treatment 1 Intervention

Testosterone 1.62% gel will be applied daily by the participants (all participants will be trained in the application process and will be given printed instructions). The intervention will be for 6 months.

Group II: placebo gel Placebo Group 1 Intervention

The placebo gel will be applied daily by the participants (all participants will be trained in the application process and will be given printed instructions). The intervention will be for 6 months.

Who Is Running the Clinical Trial?

Seattle Institute for Biomedical and Clinical Research

Lead Sponsor

Trials

55

Recruited

13,700+

Findings from Research

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]

In a study of 149 hypogonadal men, the novel testosterone 2% gel (Fortesta™ Gel) effectively restored testosterone levels to the normal range in 77.5% of patients after 90 days, demonstrating its efficacy as a testosterone replacement therapy.

The gel was generally well tolerated, with mild to moderate skin reactions being the most common side effects, and only 1.6% of patients experienced testosterone levels that were higher than the recommended range, indicating a low risk of adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel testosterone 2% gel for the treatment of hypogonadal males. Dobs, AS., McGettigan, J., Norwood, P., et al.[2013]

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]

The Testosterone Trials were designed as a coordinated set of seven clinical trials to definitively assess the efficacy of testosterone treatment in elderly men with low testosterone levels, focusing on various health aspects such as mobility, sexual function, and cognitive abilities.

The trials aimed to improve the reliability of results by using common eligibility criteria and treatment approaches, although the rigorous screening process required evaluating about 30 men to enroll just one participant, ensuring that only those with unequivocally low testosterone were included.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men. Snyder, PJ., Ellenberg, SS., Cunningham, GR., et al.[2021]

Testosterone gel 2% (TG) was found to be effective in increasing serum testosterone levels in hypogonadal men, with an 85.5% responder rate after 3 months of treatment in a study involving 180 participants.

The safety profile of TG was acceptable, with fewer subjects experiencing high testosterone levels (Cmax >1500 ng/dl) in the extension study, and no significant safety concerns were noted, including no notable increases in prostate-specific antigen or haematocrit levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of testosterone replacement gel for treating hypogonadism in men: Phase III open-label studies. Belkoff, L., Brock, G., Carrara, D., et al.[2018]

Testosterone gel formulations effectively restore testosterone levels to mid-normal physiological ranges within 24 hours, improving the quality of life for patients with hypogonadism.

While testosterone gels have a favorable efficacy and safety profile compared to other forms of testosterone replacement therapy, there is a risk of secondary exposure, which remains a challenge for their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new 2% testosterone gel formulation: a comparison with currently available topical preparations. Arver, S., Stief, C., de la Rosette, J., et al.[2019]

In a study involving 26 healthy male volunteers, applying 5.0 g of a 2.5% testosterone gel daily for 10 days successfully restored physiological testosterone levels, while 2.5 g was insufficient for this purpose.

Washing the gel off 10 minutes after application did not affect testosterone absorption, which helps minimize the risk of contamination for female partners or infants, enhancing the safety of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of a new transdermal testosterone gel in gonadotrophin-suppressed normal men. Rolf, C., Kemper, S., Lemmnitz, G., et al.[2019]

Topical testosterone gels can lead to unintentional transfer of testosterone to women and children through skin contact, which may result in conditions like female hyperandrogenism, as illustrated by a reported case.

Research, including case reports and clinical trials, confirms that testosterone transfer from gel-treated males is a clinically relevant risk, highlighting the need for awareness of this potential side effect in testosterone replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperandrogenism after transfer of topical testosterone gel: case report and review of published and unpublished studies. de Ronde, W.[2022]

In a pilot study of 18 men with eugonadotropic hypogonadism, transdermal testosterone gel treatment for 3 months successfully normalized testosterone levels without negatively affecting sperm production.

This suggests that testosterone gel therapy could be a promising option for treating hypogonadism in reproductive-aged men while preserving fertility, although more research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of testosterone gel treatment on spermatogenesis in men with hypogonadism. George, M., Yulia, T., Svetlana, K.[2014]

A study involving 16 men with androgen deficiency found that a novel 5% testosterone cream (AndroForte 5) and a 1% testosterone gel (Testogel) were bioequivalent, meaning they had similar pharmacokinetic profiles after 30 days of treatment.

Both testosterone formulations did not show significant differences in secondary biochemical markers, indicating that they have comparable safety and efficacy profiles for treating testosterone deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label, phase 2, single centre, randomized, crossover design bioequivalence study of AndroForte 5 testosterone cream and Testogel 1% testosterone gel in hypogonadal men: study LP101. Wittert, GA., Harrison, RW., Buckley, MJ., et al.[2016]

References

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

Impact of Adjunct Testosterone on Cancer-Related Fatigue: An Ancillary Analysis from a Controlled Randomized Trial. [2023]

2. Germany pubmed.ncbi.nlm.nih.gov

Testosterone replacement for fatigue in hypogonadal ambulatory males with advanced cancer: a preliminary double-blind placebo-controlled trial. [2021]

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

A novel testosterone 2% gel for the treatment of hypogonadal males. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Sexual functioning in testosterone-supplemented patients treated for bilateral testicular cancer. [2019]

5. England pubmed.ncbi.nlm.nih.gov

The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety of testosterone replacement gel for treating hypogonadism in men: Phase III open-label studies. [2018]

7. England pubmed.ncbi.nlm.nih.gov

A new 2% testosterone gel formulation: a comparison with currently available topical preparations. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of a new transdermal testosterone gel in gonadotrophin-suppressed normal men. [2019]

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

Hyperandrogenism after transfer of topical testosterone gel: case report and review of published and unpublished studies. [2022]

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

Influence of testosterone gel treatment on spermatogenesis in men with hypogonadism. [2014]

11. England pubmed.ncbi.nlm.nih.gov

An open-label, phase 2, single centre, randomized, crossover design bioequivalence study of AndroForte 5 testosterone cream and Testogel 1% testosterone gel in hypogonadal men: study LP101. [2016]