Testosterone for Treating Cachexia in Patients With Squamous Cell Carcinoma

Nutrition and Anabolic Interventions in Squamous Cell Carcinoma

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00878995

Enrollment

Registered

2009-04-09

Start date

2009-06-03

Completion date

2015-06-30

Last updated

2018-03-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cachexia, Squamous Cell Carcinoma

Keywords

stage IIB cervical cancer, stage III cervical cancer, recurrent cervical cancer, cachexia, advanced head/neck carcinoma, recurrent head/neck carcinoma

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.

Interventions

DRUGPlacebo Testosterone

Placebo (Saline) Testosterone given IM once per week.

DRUGTestosterone Enanthate 100 MG/ML

Testosterone Enanthate 100mg/ml given once per week IM.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 75 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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 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.
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.
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.
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).
1-year Survival	1 year post study	Number of participants who survived one year post study.
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).

Countries

United States

Participant flow

Recruitment details

Subjects were recruited via UTMB Oncology, Radiation Oncology, and ENT clinics by study physicians.

Pre-assignment details

Subjects began study before beginning chemotherapy and/or radiation therapy. 28 subjects enrolled total. 4 subjects withdrew before beginning the study.

Participants by arm

Arm	Count
Arm I: Standard of Care Therapy + Placebo Testosterone Patients receive standard of care chemotherapy and/or radiation plus placebo testosterone intramuscularly (IM) weekly for 7 weeks. Standard of Care Chemotherapy and/or Radiation plus Placebo (Saline) Testosterone: Standard of Care Chemotherapy and/or Radiation plus Placebo (Saline) Testosterone	12
Arm II: Standard of Care Therapy + Testosterone Patients receive standard of care chemotherapy and/or radiation plus testosterone intramuscularly (IM) weekly for 7 weeks. Arm II: Standard of Care Chemotherapy and/or Radiation plus Testosterone Enanthate: Arm II: Standard of Care Chemotherapy and/or Radiation plus Testosterone Enanthate	12
Total	24

Withdrawals & dropouts

Period	Reason	FG000	FG001
Baseline Study - Midpoint Study	Withdrawal by Subject	0	2

Baseline characteristics

Characteristic	Arm I: Standard of Care Therapy + Placebo Testosterone	Total	Arm II: Standard of Care Therapy + Testosterone
Age, Continuous	54 years STANDARD_DEVIATION 7.97	51.44 years STANDARD_DEVIATION 10.3	48.66 years STANDARD_DEVIATION 12.26
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants	3 Participants	1 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants	21 Participants	11 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	4 Participants	2 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	10 Participants	20 Participants	10 Participants
Region of Enrollment United States	12 participants	24 participants	12 participants
Sex: Female, Male Female	5 Participants	14 Participants	9 Participants
Sex: Female, Male Male	7 Participants	10 Participants	3 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 12	0 / 12
other Total, other adverse events	6 / 12	3 / 12
serious Total, serious adverse events	6 / 12	6 / 12

Outcome results

Primary

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.

Time frame: 7 weeks

Population: Reporting data for the 22 completing subjects only, since this data is reported as change over time.

Arm	Measure	Value (MEAN)	Dispersion
Arm I: Standard of Care Therapy + Placebo Testosterone	Change in Total Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DEXA) From Baseline to 7 Weeks.	-3.31 Percent change	Standard Deviation 6.34
Arm II: Standard of Care Therapy + Testosterone	Change in Total Lean Body Mass as Measured by Dual Energy X-ray Absorptiometry (DEXA) From Baseline to 7 Weeks.	1.42 Percent change	Standard Deviation 7.25

Secondary

1-year Survival

Number of participants who survived one year post study.

Time frame: 1 year post study

Population: 12 subjects started each group. 2 subjects withdrew after baseline from the testosterone group.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Arm I: Standard of Care Therapy + Placebo Testosterone	1-year Survival	7 Participants
Arm II: Standard of Care Therapy + Testosterone	1-year Survival	6 Participants

Secondary

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.

Time frame: 7 weeks

Population: 22 subjects completed this outcome measure at the 7 week time point. 24 subjects started the study, 2 subjects dis-enrolled after the baseline visit.

Arm	Measure	Value (MEAN)	Dispersion
Arm I: Standard of Care Therapy + Placebo Testosterone	Body Weight as Measured by Scale at 7 Weeks.	63.93 Kilograms	Standard Deviation 24.79
Arm II: Standard of Care Therapy + Testosterone	Body Weight as Measured by Scale at 7 Weeks.	62.59 Kilograms	Standard Deviation 17.83

Secondary

Body Weight as Measured by Scale at Baseline

Body weight in kilograms as measured by a scale at the baseline visit.

Time frame: Baseline

Population: 24 subjects began the study. Each subjects was able to complete this outcome measure at the baseline time point.

Arm	Measure	Value (MEAN)	Dispersion
Arm I: Standard of Care Therapy + Placebo Testosterone	Body Weight as Measured by Scale at Baseline	65.98 Kilograms	Standard Deviation 25.49
Arm II: Standard of Care Therapy + Testosterone	Body Weight as Measured by Scale at Baseline	63.11 Kilograms	Standard Deviation 17.24

Secondary

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.

Time frame: 7 weeks