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

Sponsor

Seattle Institute for Biomedical and Clinical Research (Other)

Overall Status

Recruiting

CT.gov ID

NCT04301765

Collaborator

(none)

230

Enrollment

Locations

Arms

59.6

Anticipated Duration (Months)

115

Patients Per Site

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hypogonadism, Male Cancer Fatigue	Drug: testosterone 1.62% gel Other: placebo gel	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

230 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

randomized, double-blind, placebo-controlled, parallel group, trial of daily transdermal testosterone gel or placebo gel for 6-monthsrandomized, double-blind, placebo-controlled, parallel group, trial of daily transdermal testosterone gel or placebo gel for 6-months

Masking:

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

Primary Purpose:

Supportive Care

Official Title:

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

Actual Study Start Date :

Jan 12, 2021

Anticipated Primary Completion Date :

Jun 30, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: testosterone 1.62% gel 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 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
Placebo Comparator: placebo gel 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 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

Arm

Intervention/Treatment

Experimental: testosterone 1.62% gel

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

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

Placebo Comparator: placebo gel

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

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

Outcome Measures

Primary Outcome Measures

Fatigue change [6 monthas]
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.

Secondary Outcome Measures

Change in Sexual Activity Score [6 months]
Secondary outcome is change in sexual activity score, assessed by the Harbor-UCLA 7-day Sexual Function Questionnaire.

Other Outcome Measures

Change in Other Measures of Sexual Function [6 months]
Erectile function will be assessed by International Index of Erective Function (IIEF).
Change in Mood and Well-being [6 months]
Mood and well-being will be assessed by Positive and Negative Affect Scale (PANAS), 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).
Body Composition Changes [6 months]
Body composition changes will be assessed by measuring lean body mass and fat mass by dual energy X-ray absorptiometry (DEXA).
Muscle Strength Changes [6 months]
Muscle strength will be assessed by measuring maximal voluntary strength in the leg press exercise by the 1-RM method;
Physical Function Changes [6 months]
physical function will be evaluated using the 6-minute walk test andwill also be evaluated by measuring power in the lower extremities by conducting the leg press exercise
Objective Measures of Habitual Physical Activity Changes [6 months]
To determine changes in daily physical activity, validated actigraphy will be used.
Caregiver Burden Changes [6 months]
The Brief Assessment Scale for Caregivers (BASC) will be used to determine caregiver burden.
Work Productivity [6 months]
Loss of productivity will be evaluated using the Work Productivity and Impairment (WPAI) scale.
Sleep Quality Changes [6 months]
Sleep quality will be assessed using the validated Pittsburgh Sleep Quality Index (PSQI) scale and by using actigraphy
Qualitative Survey [6 months]
Qualitative interviews will be performed by a study co-investigator which will assess lived experiences of participants at baseline and at 24 weeks by conducting semi-structured, qualitative phone interviews with a randomly selected sample of 30 men in the testosterone arm and 30 men in the placebo arm (equally divided across the 3 sites).

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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 24 months or less, which means that they are <24 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