Testosterone for Treating Cachexia in Patients With Squamous Cell Carcinoma

Phase 1

Completed

Conditions: Cachexia
Squamous Cell Carcinoma

Interventions: Drug: Testosterone Enanthate 100 MG/ML
Drug: Placebo Testosterone

Registration Number: NCT00878995

Lead Sponsor: The University of Texas Medical Branch, Galveston

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 28

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care Therapy + Testosterone	Testosterone Enanthate 100 MG/ML	Patients receive standard of care chemotherapy and/or radiation plus testosterone (Testosterone Enanthate 100mg/ml) intramuscularly (IM) weekly for 7 weeks.
Standard of Care Therapy + Placebo Testosterone	Placebo Testosterone	Patients receive standard of care chemotherapy and/or radiation plus placebo testosterone intramuscularly (IM) weekly for 7 weeks.

Primary Outcome Measures

Name	Time	Method
Change in Total Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DEXA) From Baseline to 7 Weeks.	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.

Secondary Outcome Measures

Name	Time	Method
1-year Survival	1 year post study	Number of participants who survived one year post study.
Concentration of Cytokine Interleukin 12 (IL-12) in Blood as Measured by Immunoassay at 7 Weeks.	7 weeks	Concentration of cytokine Interleukin 12 (IL-12) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 at Baseline	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.
Maximum Peak Isometric Leg Strength as Measured by Biodex Pro 4 at 7 Weeks.	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.
Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro 4 at Baseline.	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.
Maximum Peak Isokinetic Leg Extension as Measured by Biodex Pro 4 at 7 Weeks	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.
Body Weight as Measured by Scale at Baseline	Baseline	Body weight in kilograms as measured by a scale at the baseline visit.
Body Weight as Measured by Scale at 7 Weeks.	7 weeks	Body Weight in kilograms as measured on a scale after 7 weeks of treatment with the study medication.
Energy Expenditure Reported as Kcal/Day as Measured by Indirect Calorimetry at Baseline	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.
Energy Expenditure Reported as Kcal/Day as Measured by Indirect Calorimetry at 7 Weeks	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.
Physical Activity Levels as Measured by the ActiGraph Accelerometer	through study completion,up to 7 weeks	Physical activity is reported as % time sedentary for the entire 7 week study.
Concentration of Cytokine Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) in Blood as Measured by Immunoassay at Baseline	Baseline	Concentration of cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) in Blood as Measured by Immunoassay at 7 Weeks	7 weeks	Concentration of cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interferon-gamma (IFN Gamma) in Blood as Measured by Immunoassay at Baseline.	baseline	Concentration of cytokine Interferon-gamma (IFN gamma) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interferon-gamma (IFN Gamma) in Blood as Measured by Immunoassay at 7 Weeks	7 weeks	Concentration of cytokine Interferon-gamma (IFN gamma) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 1 Beta (IL-1B) in Blood as Measured by Immunoassay at Baseline.	Baseline	Concentration of cytokine Interleukin 1 beta (IL-1B) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 1 Beta (IL-1B) in Blood as Measured by Immunoassay at 7 Weeks.	7 weeks	Concentration of cytokine Interleukin 1 beta (IL-1B) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 2 (IL-2) in Blood as Measured by Immunoassay at Baseline.	baseline	Concentration of cytokine Interleukin 2 (IL-2) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 2 (IL-2) in Blood as Measured by Immunoassay at 7 Weeks.	7 weeks	Concentration of cytokine Interleukin 2 (IL-2) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 4 (IL-4) in Blood as Measured by Immunoassay at Baseline.	baseline	Concentration of cytokine Interleukin 4 (IL-4) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 4 (IL-4) in Blood as Measured by Immunoassay at 7 Weeks.	7 weeks	Concentration of cytokine Interleukin 4 (IL-4) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 5 (IL-5) in Blood as Measured by Immunoassay at Baseline.	Baseline	Concentration of cytokine Interleukin 5 (IL-5) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 5 (IL-5) in Blood as Measured by Immunoassay at 7 Weeks.	7 weeks	Concentration of cytokine Interleukin 5 (IL-5) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 6 (IL-6) in Blood as Measured by Immunoassay at Baseline.	baseline	Concentration of cytokine Interleukin 6 (IL-6) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 6 (IL-6) in Blood as Measured by Immunoassay at 7 Weeks.	7 weeks	Concentration of cytokine Interleukin 6 (IL-6) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 7 (IL-7) in Blood as Measured by Immunoassay at Baseline.	Baseline	Concentration of cytokine Interleukin 7 (IL-7) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 7 (IL-7) in Blood as Measured by Immunoassay at 7 Weeks.	7 weeks	Concentration of cytokine Interleukin 7 (IL-7) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 8 (IL-8) in Blood as Measured by Immunoassay at Baseline.	Baseline	Concentration of cytokine Interleukin 8 (IL-8) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 8 (IL-8) in Blood as Measured by Immunoassay at 7 Weeks.	7 weeks	Concentration of cytokine Interleukin 8 (IL-8) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 10 (IL-10) in Blood as Measured by Immunoassay at Baseline.	baseline	Concentration of cytokine Interleukin 10 (IL-10) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 10 (IL-10) in Blood as Measured by Immunoassay at 7 Weeks.	7 weeks	Concentration of cytokine Interleukin 10 (IL-10) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 12 (IL-12) in Blood as Measured by Immunoassay at Baseline.	Baseline	Concentration of cytokine Interleukin 12 (IL-12) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 13 (IL-13) in Blood as Measured by Immunoassay at Baseline.	Baseline	Concentration of cytokine Interleukin 13 (IL-13) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Interleukin 13 (IL-13) in Blood as Measured by Immunoassay at 7 Weeks.	7 weeks	Concentration of cytokine Interleukin 13 (IL-13) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Tumor Necrosis Factor Alpha (TNFa) in Blood as Measured by Immunoassay at Baseline.	baseline	Concentration of cytokine tumor necrosis factor alpha (TNFa) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Concentration of Cytokine Tumor Necrosis Factor Alpha (TNFa) in Blood as Measured by Immunoassay at 7 Weeks.	7 weeks	Concentration of cytokine tumor necrosis factor alpha (TNFa) in blood as measured using Millipore Multiplex Human Cytokine Panel assay.
Fat Mass as Measured by Dual Energy XRay Absorptiometry (DEXA) at Baseline	baseline	Total Fat Mass as measured by dual energy xray absorptiometry at the baseline study visit
Fat Mass as Measured by Dual Energy XRay Absorptiometry (DEXA) at 7 Weeks	7 weeks	Total fat mass as measured by Dual Energy XRay Absorptiometry (DEXA) at the 7 week study visit.
Quality of Life Measurement as Measured by Medical Outcome Study - Short Form 36 at Baseline	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.
Quality of Life Measurement as Measured by Medical Outcome Study - Short Form 36 at 7 Weeks	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
Personal Perception of Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form at Baseline	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.
Personal Perceptual Fatigue Measured by Multidimensional Fatigue Symptom Inventory at 7 Weeks	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.
Mood Measured by Profile of Mood States at Baseline	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).
Mood as Measured by Profile of Mood States at 7 Weeks	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).
Quality of Life as Measured by Functional Assessment of Cancer Therapy - General Questionnaire at Baseline	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).
Quality of Life as Measured by Functional Assessment of Cancer Therapy - General Questionnaire at 7 Weeks	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).