Testosterone for Treating Cachexia in Patients With Advanced or Recurrent Cervical Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by The University of Texas, Galveston
Sponsor:
Collaborator:
Information provided by (Responsible Party):
The University of Texas, Galveston
ClinicalTrials.gov Identifier:
NCT00878995
First received: April 8, 2009
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

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 advanced or recurrent cervical cancer to maintain their body weight and muscle size and strength during treatment.


Condition Intervention Phase
Cachexia
Cervical Cancer
Drug: Standard of Care Chemotherapy and/or Radiation plus Placebo (Saline) Testosterone
Drug: Arm II: Standard of Care Chemotherapy and/or Radiation plus Testosterone Enanthate
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Nutrition and Anabolic Interventions in Cancer Cachexia

Resource links provided by NLM:


Further study details as provided by The University of Texas, Galveston:

Primary Outcome Measures:
  • Total lean body mass and regional muscle mass as measured by dual energy x-ray absorptiometry (DEXA) and leg muscle volume as measured by MRI at baseline and 7 weeks. [ Time Frame: Baseline and 7 weeks ] [ Designated as safety issue: No ]
  • Muscle strength and fatigue tests, including tests of maximal voluntary contraction (isometric, isotonic and isokinetic arm and leg strength on Biodex) at baseline and 7 weeks [ Time Frame: Baseline and 7 weeks ] [ Designated as safety issue: No ]
  • Changes in basal muscle protein synthesis and breakdown as measured by stable isotope metabolic studies at baseline and 7 weeks [ Time Frame: Baseline and 7 weeks ] [ Designated as safety issue: No ]
  • Changes in serum inflammatory biomarkers and muscle inflammatory cytokines as measured by immunoassay at baseline and 7 weeks [ Time Frame: Baseline and 7 weeks ] [ Designated as safety issue: No ]
  • Changes in Messenger RNA (mRNA) levels of Atrogin-1, MuRF1, and ubiquitin as measured by quantitative real-time PCR at baseline and 7 weeks [ Time Frame: Baseline and 7 weeks ] [ Designated as safety issue: No ]
  • Changes in NF-kB expression as measured by western analysis at baseline and 7 weeks [ Time Frame: Baseline and 7 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in body weight and fat mass as measured by DEXA at baseline and 7 weeks [ Time Frame: Baseline and 7 weeks ] [ Designated as safety issue: No ]
  • Change in the protein expression of anabolic and catabolic markers in the skeletal muscle as measured by western blotting at baseline and 7 weeks [ Time Frame: Baseline and 7 weeks ] [ Designated as safety issue: No ]
  • Energy expenditure and substrate oxidation as measured by indirect calorimetry using expired gases collected and analyzed for oxygen and carbon dioxide concentrations [ Time Frame: Baseline and 7 weeks ] [ Designated as safety issue: No ]
  • Quality of Life Measurements. [ Time Frame: Weekly ] [ Designated as safety issue: No ]
    Mood, fatigue, and quality of life as measured by the Medical Outcome Study-Short Form - 36 items (MOS-SF-36), the FACT-G, the Multidimensional Fatigue Symptom Inventory, the Profile of Mood States-Short Form (POMS-SF), the MD Anderson Symptom Inventory (MDASI), and the MD Anderson Brief Fatigue Inventory questionnaires

  • Physical activity levels, intensities, and energy expenditure as measured by the ActiGraph accelerometer (worn on the hip or ankle) [ Time Frame: Daily ] [ Designated as safety issue: No ]
  • 1-year survival [ Time Frame: monthly ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: April 2008
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 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.
Drug: Standard of Care Chemotherapy and/or Radiation plus Placebo (Saline) Testosterone
Standard of Care Chemotherapy and/or Radiation plus Placebo (Saline) Testosterone
Active Comparator: Arm II: Standard of Care Therapy + Testosterone
Patients receive standard of care chemotherapy and/or radiation plus testosterone intramuscularly (IM) weekly for 7 weeks.
Drug: Arm II: Standard of Care Chemotherapy and/or Radiation plus Testosterone Enanthate
Arm II: Standard of Care Chemotherapy and/or Radiation plus Testosterone Enanthate

Detailed Description:

OBJECTIVES:

  • To determine the effect of testosterone therapy on lean body mass and muscle strength in patients with advanced or recurrent cervical carcinoma and cachexia.
  • To determine the effect of testosterone therapy on muscle protein synthesis and breakdown in patients with advanced or recurrent cervical carcinoma and cachexia.
  • To determine the testosterone therapy on inflammatory biomarkers and signaling pathways involved in the regulation of muscle atrophy in patients with advanced or recurrent cervical carcinoma and cachexia.

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, MRI scan, 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 saliva samples are collected periodically for laboratory studies. Samples are analyzed for serum inflammatory biomarkers and inflammatory cytokines by immunoassay; (Atrogin-1) a muscle-specific F-box protein highly expressed during muscle atrophy, Muscle-specific RING-finger protein 1(MuRF1), and ubiquitin expression by quantitative real-time polymerase chain reaction(PCR); and Nuclear Factor-KappaB (NF-kB) expression by western analysis.

After completion of study treatment, patients are followed periodically for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of advanced (stage IIB, IIIA, or IIIB) or recurrent cervical carcinoma
  • Weight loss of ≥ 10% within the past 6 months
  • No ovarian tumors (e.g., Sertoli-Leydig cell tumor) or androgen-secreting tumors of the ovary or adrenal gland

PATIENT CHARACTERISTICS:

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Mini Mental State Examination score > 23
  • Not pregnant
  • No evidence of hepatitis as indicated by a 3-fold increase in 2 out of 3 liver enzymes
  • No significant liver, renal, or heart disease
  • No diabetes mellitus or other untreated endocrine disease
  • No polycystic ovary syndrome and/or hyperthecosis
  • No non-classical adrenal hyperplasia
  • No Cushing's syndrome
  • No glucocorticoid resistance
  • No hyperprolactinoma or hypothyroidism
  • No lactose intolerance
  • No alcohol or drug abuse
  • No other circumstance that would preclude study participation, in the opinion of the principal investigator or study physician

PRIOR CONCURRENT THERAPY:

  • More than 3 months since prior anabolic steroids
  • No concurrent anticoagulant therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00878995

Locations
United States, Texas
University of Texas Medical Branch Recruiting
Galveston, Texas, United States, 77555-0361
Contact: Clinical Trials Office - University of Texas Medical Branch    409-772-1950      
Sponsors and Collaborators
The University of Texas, Galveston
Investigators
Principal Investigator: Melinda Sheffield-Moore, PhD University of Texas
  More Information

Additional Information:
No publications provided

Responsible Party: The University of Texas, Galveston
ClinicalTrials.gov Identifier: NCT00878995     History of Changes
Other Study ID Numbers: 06-073, R01CA127971, CDR0000629579, GCRC#724
Study First Received: April 8, 2009
Last Updated: June 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas, Galveston:
stage IIB cervical cancer
stage III cervical cancer
recurrent cervical cancer
cachexia

Additional relevant MeSH terms:
Cachexia
Uterine Cervical Neoplasms
Emaciation
Weight Loss
Body Weight Changes
Body Weight
Signs and Symptoms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Antineoplastic Agents
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Therapeutic Uses
Anabolic Agents

ClinicalTrials.gov processed this record on July 26, 2014