Testosterone in Metastatic Renal Cell Carcinoma Patients

Study Overview
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Brief Summary
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Purpose To determine efficacy and safety of Testosterone in male patients with metastatic renal cell carcinoma and fatigue receiving targeted therapy or checkpoint inhibitors.

Detailed Description
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Fatigue is a frequent symptom of metastatic renal cell carcinoma (RCC), and most common adverse event of targeted and immunotherapy. In Phase 3 pivotal studies, 56% (9%, grade 3-4), 54% (11%, grade 3), 37% (10%, grade 3-4) and 20% (2%, grade 3) of patients had fatigue during the therapy of cabozantinib, sunitinib, axitinib or pazopanib, respectively. 59% (14%, grade 3) and 31% (5%, grade 3) of patients treated with lenvatinib/everolimus and everolimus had fatigue in registrational trials. Finally, 33% (2%, grade 3-4) of patients that received nivolumab had fatigue in CheckMate 025 study. Testosterone may help to relieve fatigue associated with the use of tyrosine kinase, mTOR or checkpoint inhibitors. Additionally, testosterone could impact on poor prognostic factors of RCC (anemia, ECOG performance status, serum calcium). This will be first clinical trial which evaluates safety and efficacy of Testosterone in RCC patients.

Official Title
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Phase 2 Randomized Study of Efficacy and Safety of Testosterone in Metastatic Renal Cell Carcinoma Patients With Fatigue

Conditions
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Metastatic Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Testosterone undecanoate and sunitinib or pazopanib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven clear cell renal cell carcinoma; CT-confirmed metastatic measurable disease; First-line sunitinib or pazopanib treatment with fatigue; Low level of testosterone; 4. Male, 18 years and older; 5. Normal PSA level Exclusion Criteria: Prostate and other cancers history Hypothyroidism History of serious cardiac arrhythmia, congestive heart failure, angina pectoris, or other severe cardiovascular disease (i.e., New York Heart Association class III or IV)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Testosterone and Targeted therapy<br>Testosterone undecanoate (Nebido®) and Targeted therapy (sunitinib or pazopanib) | Drug: Testosterone undecanoate and sunitinib or pazopanib<br>* Testosterone undecanoate (Nebido®) 1,000 mg (4 ml) intramuscular deeply, once before targeted therapy (sunitinib 50 mg 4/2 or pazopanib 800 mg daily)<br>|
| Active Comparator: Control<br>Targeted therapy (sunitinib or pazopanib) only | Drug: Testosterone undecanoate and sunitinib or pazopanib<br>* Testosterone undecanoate (Nebido®) 1,000 mg (4 ml) intramuscular deeply, once before targeted therapy (sunitinib 50 mg 4/2 or pazopanib 800 mg daily)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | Difference in mean change of Fatigue from baseline score with testosterone vs. without testosterone. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Safety and tolerability of testosterone (CTCAE v.4.03) | 3 months | 
| Quality of life | Health-related quality of life (NCCN-FACT FKSI-19 (Version 2) | 3 months | 
| Overall rate of adverse events | Overall rate of adverse events related with TKI treatment (CTCAE v.4.03) | 3 months | 
| Testosterone serum concentrations | Maximum and minimum total testosterone serum concentrations following dose administration at week 12 | 12 weeks | 
| Red blood cell count and Hemoglobin concentration | Change in Red blood cell count and Hemoglobin concentration following dose administration at week 12 | 12 weeks | 
| Serum calcium concentration | Change in serum calcium concentration following dose administration at week 12 | 12 weeks | 
| ECOG PS | ECOG Performance status | 3 months | 
| Overall survival | Time from randomization to death | 2 years |