Testosterone Replacement in Male Cancer Survivors With Fatigue and Low Testosterone

Sponsor

Seattle Institute for Biomedical and Clinical Research (Other)

Overall Status

Recruiting

CT.gov ID

NCT04049331

Collaborator

(none)

240

Enrollment

Locations

Arms

61.3

Anticipated Duration (Months)

120

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The overall goal of this study is to evaluate the effect of a testosterone drug called Depo-Testosterone (or 'testosterone cypionate'), an FDA-approved drug for improving fatigue, sexual function, quality of life, body composition, muscle strength, and physical activity in young cancer survivors who report fatigue and have low testosterone. Main hypothesis is that Testosterone administration in young male cancer survivors who are in remission for at least 1 year, report cancer-related fatigue and have symptomatic testosterone deficiency will be associated with greater improvements in fatigue scores compared with placebo.

Condition or Disease	Intervention/Treatment	Phase
Hypogonadism, Male Fatigue Syndrome, Chronic	Drug: Testosterone Undecanoate 750 MG/3 ML Intramuscular Solution [AVEED] Other: placebo	Phase 2

Detailed Description

The overall goal of this proposal is to evaluate the efficacy of testosterone replacement therapy in improving fatigue and other outcomes such as sexual function, quality of life, body composition, muscle strength and physical activity in a double-blind, randomized, placebo-controlled trial in young cancer survivors who report fatigue and have testosterone deficiency.

Fatigue is one of the most prevalent and debilitating symptoms in men with cancer affecting 70-100% of patients irrespective of their age. Cancer-related fatigue is experienced by patients not only during active cancer treatment, but is also highly prevalent in cancer survivors who exhibit persistent fatigue months to years after the end of their treatment with the highest prevalence being in recipients of chemotherapy and/or radiation therapy.

In addition to fatigue, sexual dysfunction is also highly prevalent in male cancer survivors. Male cancer survivors also have increased fat mass and decreased lean body mass, a phenotype that predisposes them to reduced muscle strength. This phenotype of fatigue, sexual dysfunction and adverse body composition is commonly encountered in non-cancer patient populations with testosterone deficiency, a condition which is also highly prevalent (50-90%) in cancer survivors. Pivotal trials of testosterone replacement therapy in non-cancer patient populations have shown an improvement in fatigue, sexual function and body composition in men randomized to testosterone compared with placebo. However, the efficacy of testosterone replacement therapy on cancer-related fatigue has not been studied.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

240 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Improving Patient-Important Outcomes With Testosterone Replacement in Hypogonadal Men With a Prior History of Cancer

Actual Study Start Date :

Mar 22, 2021

Anticipated Primary Completion Date :

Apr 30, 2026

Anticipated Study Completion Date :

Apr 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Testosterone Testosterone undecanoate injection 750 MG/3 ML	Drug: Testosterone Undecanoate 750 MG/3 ML Intramuscular Solution [AVEED] first two doses four weeks apart; following three more doses every ten weeks. Other Names: study drug
Placebo Comparator: Placebo clinical grade saline 0.9% sodium chloride injection	Other: placebo first two doses four weeks apart; following three more doses every ten weeks.

Arm

Intervention/Treatment

Experimental: Testosterone

Testosterone undecanoate injection 750 MG/3 ML

Drug: Testosterone Undecanoate 750 MG/3 ML Intramuscular Solution [AVEED]

first two doses four weeks apart; following three more doses every ten weeks.

Other Names:

study drug

Placebo Comparator: Placebo

clinical grade saline 0.9% sodium chloride injection

Other: placebo

first two doses four weeks apart; following three more doses every ten weeks.

Outcome Measures

Primary Outcome Measures

Fatigue change [9 months]
(Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) questionnaire

Secondary Outcome Measures

Sexual function change [9 months]
Harbor-UCLA 7-day Sexual Function Questionnaire
Sexual function change [9 months]
International Index of Erective Function (IIEF) questionnaire
Body composition change [9 months]
Lean body mass and fat mass (kg) measured by dual energy x-ray absorptiometry (DEXA)
Changes to mood and well-being [9 months]
Mood and well-being will be assessed by the Positive and Negative Affect Scale (PANAS) affectivity balance scale, which includes 10 questions each for Positive Affect and Negative Affect. Many behavioral scientists consider affectivity as the cleanest window on an individual's wellbeing. The most sensitive indicator of impaired wellbeing has been shown to be affective dysregulation, which is reflected in affectivity balance. The latter incorporates negative affects (e.g., anxiety, depression) as well as positive affects (e.g., joy).
Muscle strength change [9 months]
Maximal voluntary muscle strength in the lower extremities will be assessed by conducting the leg press exercise by the 1-repetition maximum method and assessing loaded stair climb power.
Sleep quality change [9 months]
Pittsburgh Sleep Quality Index (PSQI)
Sleep quality change [9 months]
Insomnia Severity Index (ISI)
Sleep quality change [9 months]
Actigraphy
Daily physical activity change [9 months]
Validated triaxial accelerometry (actigraphy)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 54 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Inclusion Criteria:

Cancer survivors who have received chemotherapy and/or radiation therapy for their cancer and are now in remission for at least one year
Non-hormone-dependent cancer, including most solid tumors, lymphomas and leukemias
Age: 18-54 years
Serum testosterone, measured by mass spectrometry (gold standard method), of <348 ng/dl and/or free testosterone <70 pg/ml. The lower limits of the normal range for total testosterone in healthy young men (age 19-40 years), is 348 ng/dL and the lower limits of free testosterone is <70 pg/ml in the Framingham Heart Study sample97. Therefore, young symptomatic men with total testosterone <348 ng/dl could be considered testosterone deficient. As sex hormone binding globulin levels may be elevated in some men with cancer (resulting in elevation in total testosterone level), some of these symptomatic men may still be hypogonadal despite having total testosterone above this cut-off limit. However; their free testosterone levels may still be below the lower limit of normal. Thus, we will also include men with free testosterone <70 pg/mL.
Self-reported fatigue. We have selected these symptoms because they are commonly reported in male cancer survivors. Fatigue will be defined as a score on Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale of <40, which best divides cancer patients from the general population with 84% accuracy, and was used as the cut-off for the NIA-funded 50-million-dollar testosterone trial (The T-Trial).
Ability and willingness to provide informed consent.

Exclusion Criteria:

Men with hormone-dependent cancers (breast, prostate or adenocarcinoma of unknown origin)
Men with brain cancer (potential cognitive impairment)
Use of anabolic agents (testosterone, dehydroepiandrosterone, growth hormone) within the past 6 months
Appetite stimulating agents e.g. megestrol acetate within the past 6 months
Systemic glucocorticoids e.g. prednisone 20 mg daily or equivalent doses of other glucocorticoids for more than two weeks in the past 6 months
Baseline hematocrit >48%
PSA >4 ng/ml in Caucasians; >3 ng/ml in African-Americans; nodule/induration on digital rectal exam
Men with 1st order relatives with a history of prostate cancer
Uncontrolled congestive heart failure
Severe untreated sleep apnea
Myocardial infarction, acute coronary syndrome, revascularization surgery, or stroke within 3 months