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RecruitingNCT04049331Updated Jun 22, 2026

Testosterone Replacement in Male Cancer Survivors With Fatigue and Low Testosterone

A Phase 2 interventional study of Testosterone Undecanoate 750 MG/3 ML Intramuscular Solution [AVEED] and placebo in Hypogonadism, Male and Fatigue Syndrome, Chronic, sponsored by Seattle Institute for Biomedical and Clinical Research. Recruiting at 2 sites in United States. Open to male participants aged 18 Years to 54 Years. Per ClinicalTrials.gov, last updated 2026-06-22.

Sponsored by Seattle Institute for Biomedical and Clinical Research · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
240
Allocation
Randomized
Ages
18 Years to 54 Years
Sex
Male
01

Study 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.

Read the 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.

02

Conditions studied

  • Hypogonadism, Male
  • Fatigue Syndrome, Chronic

Keywords

  • testosterone
  • hypogonadism
  • cancer related fatigue
03

Who can participate

Ages eligible
18 Years to 54 Years
Sexes eligible
Male
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
240 participants (estimated)

Study arms

  • Experimental
    Testosterone

    Testosterone undecanoate injection 750 MG/3 ML

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

  • Placebo comparator
    Placebo

    clinical grade saline 0.9% sodium chloride injection

    Other: placebo

Interventions

  • DrugTestosterone Undecanoate 750 MG/3 ML Intramuscular Solution [AVEED]

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

    Also known as: study drug

  • Otherplacebo

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

05

What researchers measure

Primary outcomes

  1. Fatigue change

    (Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) questionnaire

    Time frame: 9 months

Secondary outcomes

  1. Sexual function change

    Harbor-UCLA 7-day Sexual Function Questionnaire

    Time frame: 9 months

  2. Sexual function change

    International Index of Erective Function (IIEF) questionnaire

    Time frame: 9 months

  3. Body composition change

    Lean body mass and fat mass (kg) measured by dual energy x-ray absorptiometry (DEXA)

    Time frame: 9 months

  4. 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).

    Time frame: 9 months

  5. 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.

    Time frame: 9 months

  6. Sleep quality change

    Pittsburgh Sleep Quality Index (PSQI)

    Time frame: 9 months

  7. Sleep quality change

    Insomnia Severity Index (ISI)

    Time frame: 9 months

  8. Sleep quality change

    Actigraphy

    Time frame: 9 months

  9. Daily physical activity change

    Validated triaxial accelerometry (actigraphy)

    Time frame: 9 months

06

Study locations

2 of 2 sites recruiting
  • Brigham and Women's Hospital
    Boston, Massachusetts 02115, United States
    • Milena Braga, MD · Contact · mbraga@bwh.harvard.edu · 617-525-9144
    • Shehzad Basaria, MD · Principal investigator
    Recruiting
  • Veterans Affairs Puget Sound Health Care System
    Seattle, Washington 98108, United States
    Recruiting
07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT04049331
Lead sponsor
Seattle Institute for Biomedical and Clinical Research
Responsible party
Sponsor
First posted
Aug 8, 2019
Start date
Mar 22, 2021
Primary completion
Jan 30, 2027 (estimated)
Completion
Jan 30, 2027 (estimated)
Last update
Jun 22, 2026

Study contacts

Jose M Garcia, MD, PhD
Contact
jg77@uw.edu
206 764 2984
Jose M Garcia, MD, PhD
principal investigator · VA Puget Sound Health Care System

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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