Study of GTx-024 on Muscle Wasting (Cachexia) Cancer.

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.

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