Effect of GTx-758 on Total and Free Testosterone Levels in Men With Prostate Cancer (GTx758)

This study has been terminated.
(FDA Clinical Hold)
Sponsor:
Information provided by (Responsible Party):
GTx
ClinicalTrials.gov Identifier:
NCT01326312
First received: March 25, 2011
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Prostate Cancer
Drug: GTx-758
Drug: Lupron Depot
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II, Open Label, Dose Finding Study of the Effect of GTx-758 on Total and Free Testosterone Levels in Men With Prostate Cancer Compared to a Luteinizing Hormone Releasing Hormone Agonist

Resource links provided by NLM:


Further study details as provided by GTx:

Primary Outcome Measures:
  • To determine the proportion of men who are castrate by Day 60 in those taking GTx 758 compared to those taking Lupron Depot. [ Time Frame: 60 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the proportion of men who are castrate by Day 60 and are maintained in the castrate range from Day 60 to Day 360/end of study. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • To determine the time to castration in men with prostate cancer treated with GTx-758 [ Time Frame: 60 days ] [ Designated as safety issue: No ]
  • The change from baseline to Day 60 in free testosterone in GTx-758 treatment group compared to the Lupron treatment group will be assessed. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Enrollment: 156
Study Start Date: June 2011
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GTX 758
GTx-758/Experimental/ nonsteroidal selective ER alpha agonist
Drug: GTx-758
comparison of different dosages of GTx-758 with leuprolide acetate for depot suspension
Experimental: GTx-758
GTx-758/Experimental/ nonsteroidal selective ER alpha agonist
Drug: GTx-758
comparison of different dosages of GTx-758 with leuprolide acetate for depot suspension
Active Comparator: Lupron Depot
Luteinizing Hormone Releasing Hormone Agonist
Drug: Lupron Depot
comparison of different dosages of GTx-758 with leuprolide acetate for depot suspension

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   45 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01326312

  Show 36 Study Locations
Sponsors and Collaborators
GTx
Investigators
Study Director: Mitchell Steiner, MD GTx
  More Information

No publications provided

Responsible Party: GTx
ClinicalTrials.gov Identifier: NCT01326312     History of Changes
Other Study ID Numbers: G200705
Study First Received: March 25, 2011
Last Updated: April 23, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Hormones
Leuprolide
Androgens
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents

ClinicalTrials.gov processed this record on August 19, 2014