Improving Cancer-related Fatigue, Sexual Dysfunction and Quality of Life in Older Men With Cancer and Androgen Deficiency

Study Overview
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Brief Summary
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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 incurable cancer who report fatigue and have low testosterone levels.

Detailed Description
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The overall objective is to conduct a double-blind, randomized, placebo-controlled, parallel group trial to determine the efficacy of 6 months of physiological testosterone replacement therapy in improving cancer related fatigue, sexual dysfunction, and body composition and muscle function in men 55 years and older with active lung or colorectal cancers, who report fatigue and have testosterone deficiency. There will be 5 study visits: 1) Screening, 2) Baseline, 3) 2-Week Dose Adjustment Visit, 4) Three-month visit (Week 12), and 5) Six-month visit. Testosterone or placebo gels will be applied by eligible trial participants at home; participants will be trained on gel application procedures by research personnel.

Official Title
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Improving Cancer-related Fatigue, Sexual Dysfunction and Quality of Life in Older Men With Cancer and Androgen Deficiency

Conditions
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Cancer, Fatigue, Hypogonadism, Male

Intervention / Treatment
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* Drug: testosterone 1.62% gel
* Other: placebo gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men with active lung or colorectal cancers who have received or are receiving chemo- and/or radiation therapy. Patients who have no evidence of disease (NED) for 60 months or less, which means that they are <60 months from their last treatment (chemotherapy and/or radiation therapy) will be included. Age: 55 years and older Life expectancy of at least 6 months. 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 men is 348 ng/dL and the lower limits of free testosterone is <70 pg/ml in the Framingham Heart Study sample. 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, but their free testosterone levels may still be below the lower limit of normal. Thus, men with free testosterone <70 pg/mL will be included. Fatigue. Fatigue was selected as it is a highly prevalent symptom in cancer patients. Fatigue will be defined as a score on FACIT-Fatigue subscale of <40, which best divides cancer patients from the general population with accuracy. Ability and willingness to provide informed consent Exclusion Criteria: Men with current or prior history of hormone-dependent cancers (breast, prostate) Men with brain metastases from any type of cancer Use of anabolic agents (testosterone, DHEA, growth hormone) within the past 6 months Current use of systemic glucocorticoids (unless part of the chemotherapy regimen) Appetite stimulating agents (e.g. megestrol acetate) within the past 1 month Hematocrit >48%, serum creatinine >2.5 mg/dL; ALT 3x upper limit of normal PSA >4 ng/ml; nodule or induration on digital rectal exam Severe untreated sleep apnea Uncontrolled congestive heart failure Myocardial infarction, acute coronary syndrome, revascularization surgery, stroke or thromboembolism (of any etiology) within 6 months Known history of thrombophilia due to a genetic mutation (e.g. Factor V Leiden) Previous stroke with residual cognitive or functional deficits Inability to provide informed consent; MMSE score <24 Poorly controlled diabetes as defined by hemoglobin A1c >8.5% Body mass index (BMI) >40 kg/m2 Untreated unipolar depression (treated depression is allowed) Bipolar disorder or schizophrenia

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: randomized, double-blind, placebo-controlled, parallel group, trial of daily transdermal testosterone gel or placebo gel for 6-months
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: testosterone 1.62% gel<br>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. | Drug: testosterone 1.62% gel<br>* The 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<br>|
| Placebo Comparator: placebo gel<br>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. | Other: placebo gel<br>* The 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue change | Primary outcome is change in fatigue score. Fatigue will be assessed by the Functional Assessment of Chronic Illness Therapy fatigue scale (FACIT-Fatigue)- The FACIT-Fatigue has been widely used in studies related to cancer-related fatigue and is able to detect clinically meaningful differences in fatigue scores in response to treatment. Population norms for the FACIT are also available, facilitating the interpretation of fatigue levels in patient populations. This instrument has been well-validated, is responsive to treatment and more sensitive to change in fatigue than other instruments. Score range: 0-52, the higher the score the better quality of life. | 6 monthas | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Sexual Activity Score | Secondary outcome is change in sexual activity score, assessed by the Harbor-UCLA 7-day Sexual Function Questionnaire. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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testosterone, cancer related fatigue, active cancer, hypogonadism