FDA Clinical Hold

The purpose of this study is to determine the appropriate loading and maintenance dose of GTx-758 to reach and maintain castration for the duration of the study.

The original purpose of the study was to determine the appropriate loading and maintenance dose of GTx-758 to reach and maintain castration for the duration of the study. The primary endpoint was used to assess the loading dose, while the secondary endpoint was intended to be used to assess maintenance. Due to the study being terminated early, as requested by FDA, the secondary assessment of maintenance was unable to be assessed. Hence, all summaries provided are for subjects in the two loading dose groups of 1000 mg BID and 1500mg BID only and not broken out by the maintenance dose.

Inclusion Criteria:

1. Be between age 45 and 80 years of age

2. Be able to communicate effectively with the study personnel

3. ECOG is ≤2

4. Screening serum total testosterone ≥150 ng/dL

5. Have prostate cancer, confirmed by pathology report

6. Have not been treated with ADT (chemical or surgical). If a subject has been treated with LHRHa for ≤6 months duration and that treatment was ≥1 years prior to the screening, the subject may be considered for the study.

7. Have a clinical indication for the initiation ADT.

8. Give written informed consent prior to any study specific procedures

9. Subjects must agree to use acceptable methods of contraception:

   • If their female partners are pregnant or lactating acceptable methods of contraception from the time of the first administration of study medication until 3 months following administration of the last dose of study medication must be used. Acceptable methods are: Condom used with spermicidal foam/gel/film/cream/suppository. If the subject has undergone surgical sterilization (vasectomy with documentation of azospermia) a condom with spermicidal foam/gel/film/cream/suppository should be used.
   • If the male subject's partner could become pregnant, use acceptable methods of contraception from the time of the first administration of study medication until 3 months following administration of the last dose of study medication. Acceptable methods of contraception are as follows: Condom with spermicidal foam/gel/film/cream/suppository [i.e. double barrier method of contraception], surgical sterilization (vasectomy with documentation of azospermia) and a double barrier method (condom used with spermicidal foam/gel/film/cream/suppository), the female partner uses oral contraceptives (combination estrogen/progesterone pills), injectable progesterone or subdermal implants and a double barrier method (condom used with spermicidal foam/gel/film/cream/suppository).
   • If the female partner has undergone documented tubal ligation (female sterilization), a double barrier method (condom used with spermicidal foam/gel/film/cream/suppository) should also be used.
   • If the female partner has undergone documented placement of an intrauterine device (IUD) or intrauterine system (IUS), a double barrier method (condom with spermicidal foam/gel/film/cream/suppository) should also be used.

Exclusion Criteria:

1. Known hypersensitivity or allergy to estrogen or estrogen like drugs
2. Have, in the judgment of the Investigator, 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 (venous or arterial thrombotic events such as history of myocardial infarct (MI), stroke, deep vein thrombosis (DVT), and/or pulmonary embolus (PE)) NOTE: if there is evidence of an MI on the ECG that is not documented in the medical history or there is a history of MI greater than three years ago that has completely resolved, the eligibility of this subject per this exclusion criterion is an investigator decision and may require a consultation with a cardiologist.
4. Have ALT or AST above 2 times the upper limit of normal (ULN)
5. Have alkaline phosphatase greater than 3 times ULN and/or total bilirubin levels above 2 mg/dL at baseline
6. Patients cannot have brain or spinal cord metastases
7. Patients cannot have or be at high 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 (the subject may be considered for randomization after a 4 week washout period prior to 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 into this study
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 480 msec two additional ECGs are to be performed separated at least 5 min apart, then take the average of the three QTcB readings to determine if the subject satisfies the above criteria. If the average QTcB reading is > 480 msec then the subject is excluded.