Clinical trial NCT04049331: Testosterone Replacement in Male Cancer Survivors With Fatigue and Low Testosterone
Official title: Improving Patient-Important Outcomes With Testosterone Replacement in Hypogonadal Men With a Prior History of Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hypogonadism, Male
Fatigue Syndrome, Chronic
Keywords: testosterone
hypogonadism
cancer related fatigue
Lead sponsor: Seattle Institute for Biomedical and Clinical Research
Sponsor class: OTHER
First posted: 2019-08-08
Enrollment: 240
Sex: MALE
Minimum age (years): 18
Maximum age (years): 54
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Fatigue change
timeFrame: 9 months
Secondary outcomes:
measure: Sexual function change
timeFrame: 9 months
measure: Sexual function change
timeFrame: 9 months
measure: Body composition change
timeFrame: 9 months
measure: Changes to mood and well-being
timeFrame: 9 months
measure: Muscle strength change
timeFrame: 9 months
measure: Sleep quality change
timeFrame: 9 months
measure: Sleep quality change
timeFrame: 9 months
measure: Sleep quality change
timeFrame: 9 months
measure: Daily physical activity change
timeFrame: 9 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Seattle
country: United States
facility: Veterans Affairs Puget Sound Health Care System
state: Washington
Study officials:
affiliation: VA Puget Sound Health Care System
name: Jose M Garcia, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: