Clinical trial NCT01326312: Effect of GTx-758 on Total and Free Testosterone Levels in Men With Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer
Lead sponsor: GTx
Sponsor class: INDUSTRY
First posted: 2011-03-30
Enrollment: 159
Sex: MALE
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: Number of Participants Who Are Castrate by Day 60
timeFrame: 60 days
Secondary outcomes:
measure: Number of Participants Who Are Castrate by Day 60 and Maintained Castrate Range From Day 60 to Day 360/End of Study.
timeFrame: 12 months
measure: Time to Castration in Participants With Prostate Cancer
timeFrame: 60 days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: GTx Investigative Site
state: Arizona
city: La Mesa
country: United States
facility: GTx Investigative Site
state: California
city: Los Angeles
country: United States
facility: GTx Investigative Site
state: California
city: San Bernardino
country: United States
facility: GTx Investigative Site
state: California
city: Middlebury
country: United States
facility: GTx Investigative Site
state: Connecticut
city: Aventura
country: United States
facility: GTx Investigative Site
state: Florida
city: Daytona Beach
country: United States
facility: GTx Investigative Site
state: Florida
city: Wellington
country: United States
facility: GTx Investigative Site
state: Florida
city: Marietta
country: United States
facility: GTx Investigative Site
state: Georgia
city: Springfield
country: United States
facility: GTx Investigative Site
state: Illinois
city: Fort Wayne
country: United States
facility: GTx Investigative Site
state: Indiana
city: Indianapolis
country: United States
facility: GTx Investigative Site
state: Indiana
city: Jeffersonville
country: United States
facility: GTx Investigative Site
state: Indiana
city: Annapolis
country: United States
facility: GTx Investigative Site
state: Maryland
city: Baltimore
country: United States
facility: GTx Investigative Site
state: Maryland
city: Brick
country: United States
facility: GTx Investigative Site
state: New Jersey
city: Lawrenceville
country: United States
facility: GTx Investigative Site
state: New Jersey
city: Albuquerque
country: United States
facility: GTx Investigative Site
state: New Mexico
city: Albany
country: United States
facility: GTx Investigative Site
state: New York
city: Garden City
country: United States
facility: GTx Investigative Site
state: New York
city: New York
country: United States
facility: GTx Investigative Site
state: New York
city: Oneida
country: United States
facility: GTx Investigative Site
state: New York
city: Syracuse
country: United States
facility: GTx Investigative Site
state: New York
city: Chapel Hill
country: United States
facility: GTx Investigative Site
state: North Carolina
city: Raleigh
country: United States
facility: GTx Investigative Site
state: North Carolina
city: Cincinnati
country: United States
facility: GTx Investigative Site
state: Ohio
city: Columbus
country: United States
facility: GTx Investigative Site
state: Ohio
city: Bala-Cynwyd
country: United States
facility: GTx Investigative Site
state: Pennsylvania
city: Lancaster
country: United States
facility: GTx Investigative Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GTx Investigative Site
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: GTx Investigative Site
state: South Carolina
city: Memphis
country: United States
facility: GTx Investigative Site
state: Tennessee
city: Nashville
country: United States
facility: GTx Investigative Site
state: Tennessee
city: Arlington
country: United States
facility: GTx Investigative Site
state: Texas
city: Houston
country: United States
facility: GTx Investigative Site
state: Texas
city: San Antonio
country: United States
facility: GTx Investigative Site
state: Texas
Study officials:
affiliation: GTx
name: Mitchell Steiner, MD
role: STUDY_DIRECTOR
References: