Testosterone for Treating Cachexia in Patients With Squamous Cell Carcinoma

Nutrition and Anabolic Interventions in Squamous Cell Carcinoma

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.

Study Overview

• Status: Completed
• Conditions: Cachexia; Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Placebo Testosterone; Drug: Testosterone Enanthate 100 MG/ML

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Galveston, Texas, United States, 77555-0361
      • University of Texas Medical Branch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Texas Medical Branch, Galveston
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Melinda Sheffield-Moore, PhD, University of Texas

Publications and helpful links

General Publications

• Scott JM, Dillon EL, Kinsky M, Chamberlain A, McCammon S, Jupiter D, Willis M, Hatch S, Richardson G, Danesi C, Randolph K, Durham W, Wright T, Urban R, Sheffield-Moore M. Effects of adjunct testosterone on cardiac morphology and function in advanced cancers: an ancillary analysis of a randomized controlled trial. BMC Cancer. 2019 Aug 7;19(1):778. doi: 10.1186/s12885-019-6006-5.

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2009
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: April 8, 2009
• First Submitted That Met QC Criteria: April 8, 2009
• First Posted (Estimate): April 9, 2009

Study Record Updates

• Last Update Posted (Actual): March 12, 2018
• Last Update Submitted That Met QC Criteria: March 8, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: cachexia; stage IIB cervical cancer; stage III cervical cancer; recurrent cervical cancer; advanced head/neck carcinoma; recurrent head/neck carcinoma
• Additional Relevant MeSH Terms: Metabolic Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Nutrition Disorders; Body Weight; Body Weight Changes; Neoplasms, Squamous Cell; Emaciation; Weight Loss; Carcinoma; Carcinoma, Squamous Cell; Wasting Syndrome; Cachexia; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: 06-073/10-207; R01CA127971 (U.S. NIH Grant/Contract); CDR0000629579; GCRC#724/819