Testosterone Replacement in Male Cancer Survivors With Fatigue and Low Testosterone

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

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.

Study Overview

• Status: Recruiting
• Conditions: Fatigue Syndrome, Chronic; Hypogonadism, Male
• Intervention / Treatment: Drug: Testosterone Undecanoate 750 MG/3 ML Intramuscular Solution [AVEED]; Other: placebo

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 Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2

Contacts and Locations

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

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Milena Braga, MD; Phone Number: 617-525-9144; Email: mbraga@bwh.harvard.edu
      • Principal Investigator: Shehzad Basaria, MD
  • Washington
    • Seattle, Washington, United States, 98108
      • Recruiting
      • Veterans Affairs Puget Sound Health Care System
      • Contact: Gary Miranda, LPN; Phone Number: 206-277-6143; Email: Gary.Miranda@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: 18 years to 54 years (Adult)
• Accepts Healthy Volunteers: No

Description

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
• 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

  o Previous stroke with residual cognitive or functional deficits; Mini-Mental State Examination score <24

• Serum creatinine >2.5 mg/dL; ALT 3x upper limit of normal
• Poorly controlled diabetes as defined by hemoglobin A1c >8.5%; Body mass index (BMI) >45 kg/m2
• Untreated unipolar depression (treated depression with medications or counseling will be allowed
• Bipolar disorder or schizophrenia

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue change	(Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) questionnaire	9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sexual function change	Harbor-UCLA 7-day Sexual Function Questionnaire	9 months
Sexual function change	International Index of Erective Function (IIEF) questionnaire	9 months
Body composition change	Lean body mass and fat mass (kg) measured by dual energy x-ray absorptiometry (DEXA)	9 months
Changes to mood and well-being	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).	9 months
Muscle strength change	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.	9 months
Sleep quality change	Pittsburgh Sleep Quality Index (PSQI)	9 months
Sleep quality change	Insomnia Severity Index (ISI)	9 months
Sleep quality change	Actigraphy	9 months
Daily physical activity change	Validated triaxial accelerometry (actigraphy)	9 months

Collaborators and Investigators

• Sponsor: Seattle Institute for Biomedical and Clinical Research
• Investigators: Principal Investigator: Jose M Garcia, MD, PhD, VA Puget Sound Health Care System

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2021
• Primary Completion (Estimated): January 30, 2026
• Study Completion (Estimated): January 30, 2026

Study Registration Dates

• First Submitted: July 23, 2019
• First Submitted That Met QC Criteria: August 6, 2019
• First Posted (Actual): August 8, 2019

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: cancer related fatigue; hypogonadism; testosterone
• Additional Relevant MeSH Terms: Nervous System Diseases; Endocrine System Diseases; Gonadal Disorders; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Fatigue; Hypogonadism; Fatigue Syndrome, Chronic; Eunuchism; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: 01751

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.: No