Testosterone for Treating Cachexia in Patients With Squamous Cell Carcinoma

Study Overview
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Brief Summary
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RATIONALE: Testosterone may lessen weight loss and improve muscle size and strength in patients with cachexia caused by cancer. PURPOSE: This randomized phase I trial is studying whether testosterone administered during standard of care chemotherapy and/or radiation works by helping patients with squamous cell carcinoma to maintain their body weight and muscle size and strength during treatment.

Detailed Description
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OBJECTIVES: To determine the effect of testosterone therapy on lean body mass and muscle strength in patients with advanced or recurrent squamous cell carcinoma. To determine the testosterone therapy on inflammatory biomarkers in patients with advanced or recurrent squamous cell carcinoma. OUTLINE: Patients are stratified according to age and disease stage. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive standard of care chemotherapy and/or radiation and placebo testosterone intramuscularly (IM) weekly for 7 weeks. Arm II: Patients receive standard of care chemotherapy and/or radiation and testosterone IM weekly for 7 weeks. Patients undergo dual energy x-ray absorptiometry, muscle strength tests, stable isotope metabolic studies, indirect calorimetry studies, and assessment of their physical activity level, and nutritional counseling. Patients also complete mood, fatigue, and quality-of-life questionnaires. Blood, muscle tissue, and urine samples are collected periodically for laboratory studies. Samples are analyzed for serum inflammatory biomarkers and inflammatory cytokines by immunoassay. After completion of study treatment, patients are followed periodically for 1 year.

Official Title
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Nutrition and Anabolic Interventions in Squamous Cell Carcinoma

Conditions
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Cachexia, Squamous Cell Carcinoma

Intervention / Treatment
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* Drug: Placebo Testosterone
* Drug: Testosterone Enanthate 100 MG/ML


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of advanced (stage IIB, IIIA, or IIIB) or recurrent squamous cell carcinoma Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Mini Mental State Examination score > 23 Exclusion Criteria: Pregnancy Evidence of hepatitis as indicated by a 3-fold increase in 2 out of 3 liver enzymes Significant liver, renal, or heart disease Diabetes mellitus or other untreated endocrine disease Polycystic ovary syndrome and/or hyperthecosis Androgen secreting tumors of the ovary and adrenal or any ovarian tumors (e.g., Sertoli- Leydig cell tumor) Non-classical adrenal hyperplasia Cushing's syndrome Glucocorticoid resistance Hyperprolactinoma or hypothyroidism Lactose intolerance Alcohol or drug abuse Recent treatment (within 3 months) with anabolic steroids Ongoing anticoagulant therapy Any other circumstance that would preclude study participation, in the opinion of the principal investigator or study physician

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Standard of Care Therapy + Placebo Testosterone<br>Patients receive standard of care chemotherapy and/or radiation plus placebo testosterone intramuscularly (IM) weekly for 7 weeks. | Drug: Placebo Testosterone<br>* Placebo (Saline) Testosterone given IM once per week.<br>|
| Active Comparator: Standard of Care Therapy + Testosterone<br>Patients receive standard of care chemotherapy and/or radiation plus testosterone (Testosterone Enanthate 100mg/ml) intramuscularly (IM) weekly for 7 weeks. | Drug: Testosterone Enanthate 100 MG/ML<br>* Testosterone Enanthate 100mg/ml given once per week IM.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Total Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DEXA) From Baseline to 7 Weeks. | Total Lean Body Mass was measured on a GE Lunar iDEXA at baseline and 7 weeks. Percent change from baseline to 7 weeks is reported. | 7 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 at Baseline | Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction. There was 1 set of 3 contractions at 100% force performed. | Baseline | 
| Maximum Peak Isometric Leg Strength as Measured by Biodex Pro 4 at 7 Weeks. | Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 5 seconds of force production for each contraction. There was 1 set of 3 contractions at 100% force performed. This outcome was measured after 7 weeks of treatment with study medication. | 7 weeks | 
| Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro 4 at Baseline. | Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 1 set of 3 contractions were performed at 100% force. | Baseline | 
| Maximum Peak Isokinetic Leg Extension as Measured by Biodex Pro 4 at 7 Weeks | Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion set at a fixed speed of 120 degree/sec. | 7 weeks | 
| Body Weight as Measured by Scale at Baseline | Body weight in kilograms as measured by a scale at the baseline visit. | Baseline | 
| Body Weight as Measured by Scale at 7 Weeks. | Body Weight in kilograms as measured on a scale after 7 weeks of treatment with the study medication. | 7 weeks | 
| Energy Expenditure Reported as Kcal/Day as Measured by Indirect Calorimetry at Baseline | Energy expenditure and substrate oxidation as measured by indirect calorimetry using expired gases collected and analyzed for oxygen and carbon dioxide concentrations. 30 minutes of sampling was performed, the last 25 minutes were averaged to calculate mean Kcal/day values. | Baseline | 
| Energy Expenditure Reported as Kcal/Day as Measured by Indirect Calorimetry at 7 Weeks | Energy expenditure and substrate oxidation as measured by indirect calorimetry using expired gases collected and analyzed for oxygen and carbon dioxide concentrations. 30 minutes of sampling was performed, the last 25 minutes were averaged to calculate mean Kcal/day values. | 7 weeks | 
| Physical Activity Levels as Measured by the ActiGraph Accelerometer | Physical activity is reported as % time sedentary for the entire 7 week study. | through study completion,up to 7 weeks | 
| Concentration of Cytokine Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) in Blood as Measured by Immunoassay at Baseline | Concentration of cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | Baseline | 
| Concentration of Cytokine Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) in Blood as Measured by Immunoassay at 7 Weeks | Concentration of cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Interferon-gamma (IFN Gamma) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine Interferon-gamma (IFN gamma) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | baseline | 
| Concentration of Cytokine Interferon-gamma (IFN Gamma) in Blood as Measured by Immunoassay at 7 Weeks | Concentration of cytokine Interferon-gamma (IFN gamma) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Interleukin 1 Beta (IL-1B) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine Interleukin 1 beta (IL-1B) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | Baseline | 
| Concentration of Cytokine Interleukin 1 Beta (IL-1B) in Blood as Measured by Immunoassay at 7 Weeks. | Concentration of cytokine Interleukin 1 beta (IL-1B) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Interleukin 2 (IL-2) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine Interleukin 2 (IL-2) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | baseline | 
| Concentration of Cytokine Interleukin 2 (IL-2) in Blood as Measured by Immunoassay at 7 Weeks. | Concentration of cytokine Interleukin 2 (IL-2) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Interleukin 4 (IL-4) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine Interleukin 4 (IL-4) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | baseline | 
| Concentration of Cytokine Interleukin 4 (IL-4) in Blood as Measured by Immunoassay at 7 Weeks. | Concentration of cytokine Interleukin 4 (IL-4) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Interleukin 5 (IL-5) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine Interleukin 5 (IL-5) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | Baseline | 
| Concentration of Cytokine Interleukin 5 (IL-5) in Blood as Measured by Immunoassay at 7 Weeks. | Concentration of cytokine Interleukin 5 (IL-5) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Interleukin 6 (IL-6) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine Interleukin 6 (IL-6) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | baseline | 
| Concentration of Cytokine Interleukin 6 (IL-6) in Blood as Measured by Immunoassay at 7 Weeks. | Concentration of cytokine Interleukin 6 (IL-6) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Interleukin 7 (IL-7) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine Interleukin 7 (IL-7) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | Baseline | 
| Concentration of Cytokine Interleukin 7 (IL-7) in Blood as Measured by Immunoassay at 7 Weeks. | Concentration of cytokine Interleukin 7 (IL-7) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Interleukin 8 (IL-8) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine Interleukin 8 (IL-8) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | Baseline | 
| Concentration of Cytokine Interleukin 8 (IL-8) in Blood as Measured by Immunoassay at 7 Weeks. | Concentration of cytokine Interleukin 8 (IL-8) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Interleukin 10 (IL-10) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine Interleukin 10 (IL-10) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | baseline | 
| Concentration of Cytokine Interleukin 10 (IL-10) in Blood as Measured by Immunoassay at 7 Weeks. | Concentration of cytokine Interleukin 10 (IL-10) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Interleukin 12 (IL-12) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine Interleukin 12 (IL-12) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | Baseline | 
| Concentration of Cytokine Interleukin 12 (IL-12) in Blood as Measured by Immunoassay at 7 Weeks. | Concentration of cytokine Interleukin 12 (IL-12) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Interleukin 13 (IL-13) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine Interleukin 13 (IL-13) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | Baseline | 
| Concentration of Cytokine Interleukin 13 (IL-13) in Blood as Measured by Immunoassay at 7 Weeks. | Concentration of cytokine Interleukin 13 (IL-13) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Concentration of Cytokine Tumor Necrosis Factor Alpha (TNFa) in Blood as Measured by Immunoassay at Baseline. | Concentration of cytokine tumor necrosis factor alpha (TNFa) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | baseline | 
| Concentration of Cytokine Tumor Necrosis Factor Alpha (TNFa) in Blood as Measured by Immunoassay at 7 Weeks. | Concentration of cytokine tumor necrosis factor alpha (TNFa) in blood as measured using Millipore Multiplex Human Cytokine Panel assay. | 7 weeks | 
| Fat Mass as Measured by Dual Energy XRay Absorptiometry (DEXA) at Baseline | Total Fat Mass as measured by dual energy xray absorptiometry at the baseline study visit | baseline | 
| Fat Mass as Measured by Dual Energy XRay Absorptiometry (DEXA) at 7 Weeks | Total fat mass as measured by Dual Energy XRay Absorptiometry (DEXA) at the 7 week study visit. | 7 weeks | 
| Quality of Life Measurement as Measured by Medical Outcome Study - Short Form 36 at Baseline | The Medical Outcome Study - Short Form 36 (MOS-SF-36) is a questionnaire developed by RAND Health to measure patient self-reported quality of life. Data presented is a subset of the questionnaire, Scale of General Health. The range for the subset presented (General Health) is 0 - 100, with 100 being better perceived health and 0 being worst perceived health. The national average of the MOS-36 General Health Subscale is reported as 56.99. | baseline | 
| Quality of Life Measurement as Measured by Medical Outcome Study - Short Form 36 at 7 Weeks | The Medical Outcome Study - Short Form 36 (MOS-SF-36) is a questionnaire developed by RAND Health to measure patient self-reported quality of life. Data presented is a subset of the questionnaire, Scale of General Health. The range for the subset presented (General Health) is 0 - 100, with 100 being better perceived health and 0 being worst perceived health. The national average of the MOS-36 General Health Subscale is reported as 56.99 | 7 weeks | 
| Personal Perception of Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form at Baseline | Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the total score is -24 to 96, with the higher the number meaning more fatigue. | Baseline | 
| Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory at 7 Weeks | Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the total score is -24 to 96, with the higher the number meaning more fatigue. | 7 weeks | 
| Mood Measured by Profile of Mood States at Baseline | Profile of Mood States (POMS) is a questionnaire by MultiHealth Systems, that measures mood. In this 65 item questionnaire, subjects are asked to rate their feelings toward a statement from 0-4, with 0 being not at all' and 4 being extremely. There are 6 subscales which include, tension-anxiety, depression, anger-hostility, vigor, fatigue, and confusion. To calculate the total mood disturbance, which is what is reported here, the subscales tension-anxiety, depression, anger-hostility, fatigue and confusion are summed and vigor is subtracted. The scale range for total mood disturbance is 200 (worst) to -32 (best). | baseline | 
| Mood as Measured by Profile of Mood States at 7 Weeks | Profile of Mood States (POMS) is a questionnaire by MultiHealth Systems, that measures mood. In this 65 item questionnaire, subjects are asked to rate their feelings toward a statement from 0-4, with 0 being not at all' and 4 being extremely. There are 6 subscales which include, tension-anxiety, depression, anger-hostility, vigor, fatigue, and confusion. To calculate the total mood disturbance, which is what is reported here, the subscales tension-anxiety, depression, anger-hostility, fatigue and confusion are summed and vigor is subtracted. The scale range for total mood disturbance is 200 (worst) to -32 (best). | 7 weeks | 
| Quality of Life as Measured by Functional Assessment of Cancer Therapy - General Questionnaire at Baseline | Functional Assessment of Cancer Therapy - General (FACT-G) is a patient-reported questionnaire of quality of life. The 27 item questionnaire is separated into 4 subscales, physical well-being, social/family well-being, emotional well-being, functional well-being. These subscales are summed to calculate total score. The range for FACT-G is 0 (worst quality of life) to 108 (best quality of life). | Baseline | 
| Quality of Life as Measured by Functional Assessment of Cancer Therapy - General Questionnaire at 7 Weeks | Functional Assessment of Cancer Therapy - General (FACT-G) is a patient-reported questionnaire of quality of life. The 27 item questionnaire is separated into 4 subscales, physical well-being, social/family well-being, emotional well-being, functional well-being. These subscales are summed to calculate total score. The range for FACT-G is 0 (worst quality of life) to 108 (best quality of life). | 7 weeks | 
| 1-year Survival | Number of participants who survived one year post study. | 1 year post study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIB cervical cancer, stage III cervical cancer, recurrent cervical cancer, cachexia, advanced head/neck carcinoma, recurrent head/neck carcinoma