Clinical trial to study the effect of GTx-758 as secondary hormonal therapy on serum PSA and serum free testosterone levels who are diagnosed with castration resistant prostate cancer.

Phase 1

• Conditions: Assessments of serum total testosterone, serum free testosterone, serum SHGB and serum PSA concentrations will be made. Bone turnover markers and the incidence and frequency of hot flashes will be assessed.CT scan of abdomen /pelvis will be conducted to asses tumor progression and soft tissue or visceral metastases.Bone scan will be conducted to to assess the development of new bone metastases.; MedDRA version: 16.1Level: PTClassification code 10036909Term: Prostate cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 16.1Level: PTClassification code 10062904Term: Hormone-refractory prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-004825-26-HU
• Lead Sponsor: GTx, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-12-04
• Last Update Posted: 23 January 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 76

Inclusion Criteria

1. Be over 18 years of age.
2. Be able to communicate effectively with the study personnel
3. Have histologically confirmed prostate cancer
4. Have high risk, non-metastatic, castration resistant prostate cancer (T any – N any – M0) or have metastatic castration resistant prostate cancer (T any – N any – M1).
o Patients with non-metastatic castration resistant prostate cancer must have a PSA doubling time greater than 0 months and less than 10 months when calculated using the website below. PSA doubling time will be calculated using at least three serum PSA measurements that were obtained within 1 year prior to Day 1 of the study and that were collected over at least 3 months with a minimum of 28 days between any two successive measurements. PSA values must be greater than 0.2 ng/dL and have been obtained while the patient was maintained on ADT. The PSA doubling time will be calculated using first order kinetics and must be performed using the following website: http://nomograms.mskcc.org/Prostate/PsaDoublingTime.aspx
o Patients with metastatic castration resistant prostate cancer must have a rising serum PSA on two successive assessments at least 2 weeks apart and serum PSA levels = 2 and < 250 ng/mL or > 2 and < 250 ng/mL and a 25% increase above the nadir from the ADT.
5. ECOG performance status of 0 to 2
6. Have been treated with ADT (chemical or surgical) for at least 6 months
7. Have a castrate level of serum total testosterone (<50 ng/dL)
8. Have a history of serum PSA response on ADT. A serum PSA response is an undetectable level of serum PSA (=0.2 ng/mL) OR at least a 90% reduction in serum PSA from the serum PSA value prior to the initiation of treatment to <10 ng/mL.
9. Be continued on ADT throughout this study
10. Give written informed consent prior to any study specific procedures
11. Subjects must agree, if not already on anticoagulation therapy or aspirin, to take at least 81 mg aspirin daily throughout the duration of their participation in this study and for 30 days after completion of dosing with GTx-758.
12. 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., barrier method of contraception], surgical sterilization (vasectomy with documentation of azospermia) and a 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 barrier method {condom used with spermicidal foam/gel/film/cream/suppository}.
• If the female partner has undergone documented tubal ligation (female sterilization), a barrier method {condom used

Exclusion Criteria

1. A serum PSA value = 250 ng/mL.
2. Known hypersensitivity or allergy to estrogen or estrogen like drugs;
3. Need for urgent chemotherapy, radiation therapy or surgical intervention for prostate cancer in the opinion of the investigator;
4. Any disease or condition (medical or surgical) which might compromise the hematologic, cardiovascular, endocrine, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk;
5. Subjects with a personal history of abnormal blood clotting or thrombotic disease (venous or arterial thrombotic events such as history of stroke, deep vein thrombosis (DVT), and/or pulmonary embolus (PE));
6. Any subjects, as determined by a central laboratory, with:
a. a modified activated protein C reaction ratio < 2.5 and a Factor V Leiden gene mutation,
b. an antithrombin level below the lower limit of the normal range,
c. an antiphospholipid antibody level for Lupus anticoagulant or anticardiolipin that is indeterminate, positive, or outside the normal range, or
d. a prothrombin gene mutation;
7. Symptomatic congestive heart failure (NYHA Class III – IV), unstable angina pectoris, cardiac arrhythmia, or history of atrial fibrillation;
8. The presence of consistently abnormal laboratory values which are considered clinically significant. In addition, any subject with liver enzymes (ALT or AST) above 2 times the upper limit of normal, total bilirubin above 2 times the upper limit of normal, or serum creatinine above 1.5 times the upper limit of normal will NOT be admitted to the study.
9. Received an investigational drug within a period of 90 days prior to enrollment in the study;
10. Received the study medication (GTx-758) previously;
11. Currently taking testosterone, testosterone-like agents, megesterol acetate, 5a-reductase inhibitor (finasteride, dutasteride), or antiandrogens (bicalutamide, flutamide or nilutamide). Subjects taking a 5a-reductase inhibitor or one of these antiandrogens may be eligible if the subject undergoes a 6-week washout period after stopping therapy. The subject must have at least two rising serum PSA levels at least 2 weeks apart after therapy with the 5a-reductase inhibitor or these antiandrogens has been stopped (antiandrogen withdrawal) and complete the 6-week washout period to be eligible;
12. Have previously taken or are currently taking diethylstilbestrol, other estrogens, any estrogen antagonist (e.g.,tamoxifen), a selective estrogen receptor modulator (e.g., raloxifene), abiraterone, ketoconazole or any other inhibitor of CYP17 (17a-hydroxylase/C17,20-lyase);
13. Currently having radiation therapy to prostate for cancer control (radiation to bone to relieve pain is acceptable);
14. Have previously taken or are currently taking enzalutamide;
15. Have previously received cytotoxic chemotherapy for prostate cancer;
16. Recent hospitalization (within 30 days of screening);
17. Recent surgery (within 30 days of screening);
18. Have taken body building or fertility supplements within 4 weeks of admission into the study;
19. Have been previously diagnosed or treated for active cancer (other than prostate cancer or non-melanoma skin cancer) within the previous five years;
20. Have a BMI >35.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified