Cachexia
Conditions
Keywords
Cachexia, Muscle Wasting, Non-Small Cell Lung Cancer, Colorectal Cancer, Non-Hodgkin's Lymphoma, Stage 3 or 4 Breast Cancer, Chronis Lymphocytic Leukemia
Brief summary
The purpose of this study is to assess if Gtx-024 is effective in increasing lean body mass in subjects with muscle wasting related to cancer.
Detailed description
Cancer cachexia is characterized by a hypermetabolic state that leads to catabolism that is responsible for reductions in lean mass.These catabolic changes are accompanied by an increase in total energy expenditure, but a decrease in voluntary energy expenditure that ultimately results clinically in cachexia and its symptoms of lethargy, fatigue, weakness and general malaise (Kotler DP. Cachexia. Ann Intern Med. 2000; 133:622-634). The prevalence of cachexia increases from 50 percent at presentation to more than 80 percent before death from malignancy. In over 20 percent of cancer patients, cachexia is the cause of death (Bruera E. Anorexia, cachexia and nutrition. Br Med J 1997;315:1219-1222). Cancer cachexia leads to shorter survival, decreased response rates and increased toxicity to chemotherapy, weakness, and an overall decreased quality of life (DeWys et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am J Med. 1980 Oct;69(4):491-7). The purpose of this study is to assess the efficacy of GTx-024 on total body lean mass. Secondary endpoints include but are not limited to assessment of GTx-024 on muscle function, total body weight and total body fat mass.
Interventions
DRUGGTx-024
1 mg GTx 024
DRUGPlacebo
Matching Placebo
Sponsors
GTx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
To be eligible for participation in this study, subjects must meet all of the following criteria: * have been diagnosed with Stage 2, 3 or 4 non-small cell lung cancer or Stage 2, 3 or 4 colorectal cancer or non-hodgkin's lymphoma or chronic lymphocytic leukemia or Stage 3 or 4 breast cancer. * be prior to initiation of or between cycles of chemotherapy. * have experienced greater than or equal to 2% weight loss from the highest patient reported weight in the 6 months prior to screening for Protocol G200502 (Wt = body weight) % weight loss = (Wt at screening - highest Wt in last 6 months) / highest Wt in last 6 months x 100% * If surgery is part of the cancer treatment, screening for this study should be conducted at least 2 weeks (14 days) after surgery. * have a life expectancy of \>6 months * FEMALES - be clinically confirmed as postmenopausal * MALES - over 45 years of age * ECOG score ≤1
Exclusion criteria
Subjects with any of the following will NOT be eligible for enrollment in this study: * history of active/uncontrolled congestive heart failure, chronic hepatitis, hepatic cirrhosis, or HIV infection * Cardiovascular: No uncontrolled hypertension * Positive screen for Hepatitis B consisting of HBsAg (Hepatitis B Surface Antigen), anti-HCV (Hepatitis C Antibody), hepatitis A antibody IgM, or HIV * Currently taking testosterone, OXANDRIN® (oxandrolone), testosterone-like agents (such as DHEA, androstenedione, and other androgenic compounds, including herbals), or antiandrogens (Please note that previous therapy with testosterone and testosterone-like agents is acceptable with a 30 day wash-out. However, if the previous testosterone therapy was a long-term depot, within the past 6 months, the site should call the medical monitor for this study to determine appropriate washout period.) * Currently taking megestrol acetate (MEGACE®), dronabinol (MARINOL®), or any prescription medication intended to increase appetite or treat unintentional weight loss
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Efficacy of GTx-024 on Total Body Lean Mass. | Baseline to Four Months | Change in total body lean mass as measured by dual energy x-ray absorptiometry (DEXA)from baseline to 4 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Assess the Efficacy of GTx-024 on Muscle Function (Performance) as Measured by Stair Climb. | Four Months | Change in stair climb power from baseline to 4 months. Stair climb power is defined power (watts)=\[9.8 m/sec\*\*2\]\*\[weight (kg)\]\*\[height of 12 steps(meters)\]/ \[time (seconds) up the 12 steps\]. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GTx -024 1 mg | 53 |
| GTx-024 3 mg | 54 |
| 3 mg of Placebo Placebo | 52 |
| Total | 159 |
Baseline characteristics
| Characteristic | GTx -024 | GTx-024 | 3 mg of Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 28 Participants | 32 Participants | 28 Participants | 88 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 22 Participants | 24 Participants | 71 Participants |
| Age, Continuous | 65.7 years STANDARD_DEVIATION 10.03 | 66.3 years STANDARD_DEVIATION 10.51 | 65.6 years STANDARD_DEVIATION 8.73 | 65.9 years STANDARD_DEVIATION 9.74 |
| Region of Enrollment Argentina | 14 participants | 17 participants | 16 participants | 47 participants |
| Region of Enrollment United States | 39 participants | 37 participants | 36 participants | 112 participants |
| Sex: Female, Male Female | 19 Participants | 20 Participants | 17 Participants | 56 Participants |
| Sex: Female, Male Male | 34 Participants | 34 Participants | 35 Participants | 103 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 47 / 53 | 49 / 54 | 46 / 52 |
| serious Total, serious adverse events | 14 / 53 | 15 / 54 | 17 / 52 |
Outcome results
Primary
The Efficacy of GTx-024 on Total Body Lean Mass.
Change in total body lean mass as measured by dual energy x-ray absorptiometry (DEXA)from baseline to 4 months.
Time frame: Baseline to Four Months
Population: The number of participants were those subjects in the modified intent-to-treat population (defined as subjects with at least one post baseline DEXA for LBM) who had baseline and 4 month DEXA results for LBM (observed cases).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GTx-024 1 mg | The Efficacy of GTx-024 on Total Body Lean Mass. | 1.55 kg |
| GTx-024 3 mg | The Efficacy of GTx-024 on Total Body Lean Mass. | 0.98 kg |
| Placebo | The Efficacy of GTx-024 on Total Body Lean Mass. | 0.02 kg |
Secondary
To Assess the Efficacy of GTx-024 on Muscle Function (Performance) as Measured by Stair Climb.
Change in stair climb power from baseline to 4 months. Stair climb power is defined power (watts)=\[9.8 m/sec\*\*2\]\*\[weight (kg)\]\*\[height of 12 steps(meters)\]/ \[time (seconds) up the 12 steps\].
Time frame: Four Months
Population: The subjects were in the MITT population (had a post baseline DEXA) and had a month 4 stair climb assessment (observed cases).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GTx-024 1 mg | To Assess the Efficacy of GTx-024 on Muscle Function (Performance) as Measured by Stair Climb. | 19.93 watts |
| GTx-024 3 mg | To Assess the Efficacy of GTx-024 on Muscle Function (Performance) as Measured by Stair Climb. | 12.84 watts |
| Placebo | To Assess the Efficacy of GTx-024 on Muscle Function (Performance) as Measured by Stair Climb. | 11.34 watts |