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

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.

Study Overview

• Status: Recruiting
• Conditions: Cancer; Fatigue; Hypogonadism, Male
• Intervention / Treatment: Drug: testosterone 1.62% gel; Other: placebo gel

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 solid or hematologic (blood) 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 Type: Interventional
• Enrollment (Estimated): 230
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jose Garcia, MD, Phd; Phone Number: 206 764 2984; Email: jg77@uw.edu

Study Locations

• United States
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Recruiting
      • Georgia Cancer Center at Augusta University
      • Contact: Egidio Del Fabbro, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Principal Investigator: Shehzad Basaria, MD
      • Contact: Milena Braga, MD; Phone Number: 617-525-9144; Email: mbraga2@bwh.harvard.edu
  • Washington
    • Seattle, Washington, United States, 98108
      • Recruiting
      • Veterans Affairs Puget Sound Health Care System
      • Contact: Haley Lowe, RN, MN; Phone Number: 206-277-4253; Email: Haley.Lowe@va.gov
      • Contact: Lindsey Anderson, PhD; Phone Number: 2062776719; Email: Lindsey.Anderson5@va.gov
      • Principal Investigator: Jose M Garcia, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men with active solid or hematologic (blood) 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 prostate, breast, testicular, or adrenal cancers.
• Use of anabolic agents (testosterone, DHEA, growth hormone) within the past 6 months
• Hematocrit >48%, serum creatinine >2.5 mg/dL
• 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 >10.0%
• Body mass index (BMI) >40 kg/m2
• Bipolar disorder or schizophrenia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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 months

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Other Measures of Sexual Function	Erectile function will be assessed by International Index of Erective Function (IIEF).	6 months
Change in Mood and Well-being	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).	6 months
Body Composition Changes	Body composition changes will be assessed by measuring lean body mass and fat mass by dual energy X-ray absorptiometry (DEXA).	6 months
Objective Measures of Habitual Physical Activity Changes	To determine changes in daily physical activity, validated actigraphy will be used.	6 months
Caregiver Burden Changes	The Brief Assessment Scale for Caregivers (BASC) will be used to determine caregiver burden.	6 months
Work Productivity	Loss of productivity will be evaluated using the Work Productivity and Impairment (WPAI) scale.	6 months
Qualitative Survey	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).	6 months
Muscle Strength Changes	Muscle strength will be assessed by measuring maximal voluntary strength in the leg press exercise by the 1-RM method.	6 months
Physical Function Changes	Physical function will be evaluated using the 6-minute walk test and will also be evaluated by measuring power in the lower extremities by conducting the leg press exercise.	6 months
Sleep Quality Changes	Sleep quality will be assessed using the validated Pittsburgh Sleep Quality Index (PSQI) scale and by using actigraphy.	6 months

Collaborators and Investigators

• Sponsor: Seattle Institute for Biomedical and Clinical Research

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2021
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: March 3, 2020
• First Submitted That Met QC Criteria: March 5, 2020
• First Posted (Actual): March 10, 2020

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: February 5, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: cancer related fatigue; hypogonadism; testosterone; active cancer
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Fatigue; Hypogonadism; Eunuchism; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: AG061558

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes