FDA Clinical Hold

The purpose of this study is to determine whether GTx 758 is effective in achieving and maintaining castrate testosterone levels in men with advanced prostate cancer.

Prostate cancer is one of the most frequently diagnosed noncutaneous cancers among men in the US and is the second most common cause of cancer deaths. Patients with advanced prostate cancer undergo androgen deprivation therapy (ADT), by either LHRH agonists, LHRH antagonists, DES and other nonselective estrogens, or by bilateral orchiectomy. ADT by LHRH agonists, LHRH antagonists, or bilateral orchiectomy not only reduces testosterone, but also substantially lowers estrogen levels as estrogen is derived from the aromatization of testosterone. ADT-induced estrogen deficiency causes significant side effects which include hot flushes, gynecomastia, bone loss, decreases in bone quality and strength, osteoporosis and life-threatening fractures, adverse lipid changes, increase in body fat composition, and higher cardiovascular disease and myocardial infarction, and depression and other mood changes.

GTx-758 is a nonsteroidal selective ER agonist that suppresses LH secretion by the pituitary by feedback inhibition of the hypothalamic-pituitary-gonadal axis to induce castrate levels of testosterone. However, because it is a selective ER agonist, GTx-758 may maintain bone, does not induce hot flushes, avoids adverse lipid changes and body fat composition changes, and does not have the acute testosterone surge that are associated with other forms of ADT.

Inclusion Criteria:

1. be between age 45 and 80 years of age
2. be able to communicate effectively with study personnel
3. ECOG is < or = 2
4. screening serum total testosterone> or = 150ng/dL
5. have prostate cancer, confirmed by pathology report
6. have not been treated with androgen deprivation therapy(chemical or surgical
7. have a clinical indication for the initiation of androgen deprivation therapy
8. give written informed consent prior to any study specific procedures
9. subject must agree to use acceptable methods of contraception

Exclusion Criteria:

1. known hypersensitivity or allergy to estrogen or estrogen like drugs
2. a clinically significant concurrent illness or psychological, familial, sociological, geographical or other concomitant condition that would not permit adequate follow-up and compliance with the study protocol
3. history of abnormal blood clotting,Factor V Leiden clotting disorder, thrombotic disease
4. have ALT or AST above 2 times the upper normal limit
5. have alkaline phosphatase greater than 3 times UNL and/or bilirubin levels above 2mg/dL at baseline
6. patients cannot have brain or spinal cord metastases
7. patients cannot have or be at risk for spinal cord compression from bone metastases
8. received an investigational drug within a period of 90 days prior to enrollment in the study
9. received the study medication previously
10. currently taking testosterone, testosterone-like agents, or antiandrogens including 5-alpha reductase inhibitors within 4 weeks of randomization
11. currently taking Saw Palmetto or PC-SPES (the subject may be considered for randomization after a 4 week washout period prior to randomization)
12. have taken diethylstilbestrol or other estrogen products within the previous 12 months prior to randomization
13. have taken body building or fertility supplements within 4 weeks of admission into the study (steroids and steroid like supplements)
14. have a history of cancer other than prostate cancer, superficial bladder cancer (with no recurrence in the last 5 years) and/or non-melanoma carcinoma of the skin
15. QTcB>480 msec, If the first QTcB reading exceeds 480msec two additional ECGs are to be performed separated at least 5 min apart, then take the average of the three QTcB or readings to determine if the subject satisfies the above criteria. If the average QYcB reading is >480 msec then the subject is excluded.