Prostate Cancer
Conditions
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.
Interventions
DRUGGTx-758 1000mg
comparison of different dosages of GTx-758 with leuprolide acetate for depot suspension
DRUGLupron Depot
comparison of different dosages of GTx-758 with leuprolide acetate for depot suspension
DRUGGTx-758 2000mg
comparison of different dosages of GTx-758 with leuprolide acetate for depot suspension
Sponsors
GTx
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
45 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants Who Are Castrate by Day 60 | 60 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Are Castrate by Day 60 and Maintained Castrate Range From Day 60 to Day 360/End of Study. | 12 months | — |
| Time to Castration in Participants With Prostate Cancer | 60 days | Median time to castration was summarized using the Kaplan-Meier method. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GTx-758 1000mg GTx-758/Experimental/ nonsteroidal selective ER alpha agonist
GTx-758: comparison of different dosages of GTx-758 with leuprolide acetate for depot suspension | 53 |
| GTx-758 2000mg GTx-758/Experimental/ nonsteroidal selective ER alpha agonist
GTx-758: comparison of different dosages of GTx-758 with leuprolide acetate for depot suspension | 55 |
| Lupron Depot Luteinizing Hormone Releasing Hormone Agonist
Lupron Depot: comparison of different dosages of GTx-758 with leuprolide acetate for depot suspension | 51 |
| Total | 159 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 11 | 1 |
| Overall Study | Death | 1 | 0 | 1 |
| Overall Study | Lack of Efficacy | 13 | 7 | 1 |
| Overall Study | progressive disease | 0 | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | QTc > 500 | 0 | 1 | 0 |
| Overall Study | Study terminated by Sponsor | 8 | 32 | 46 |
| Overall Study | Treatment arm terminated | 19 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 |
Baseline characteristics
| Characteristic | GTx-758 1000mg | Total | Lupron Depot | GTx-758 2000mg |
|---|---|---|---|---|
| Age, Continuous | 68 years | 68 years | 69 years | 68 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 15 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 144 Participants | 46 Participants | 51 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 33 Participants | 10 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 124 Participants | 41 Participants | 42 Participants |
| Region of Enrollment United States | 53 participants | 159 participants | 51 participants | 55 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 53 Participants | 159 Participants | 51 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 53 | 0 / 55 | 1 / 51 |
| other Total, other adverse events | 46 / 53 | 49 / 55 | 48 / 51 |
| serious Total, serious adverse events | 11 / 53 | 6 / 55 | 4 / 51 |
Outcome results
Primary
Number of Participants Who Are Castrate by Day 60
Time frame: 60 days
Population: Per-Protocol Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GTx- 758 1000mg | Number of Participants Who Are Castrate by Day 60 | 19 participants |
| GTx-758 2000mg | Number of Participants Who Are Castrate by Day 60 | 34 participants |
| Lupron Depot | Number of Participants Who Are Castrate by Day 60 | 43 participants |
Secondary
Number of Participants Who Are Castrate by Day 60 and Maintained Castrate Range From Day 60 to Day 360/End of Study.
Time frame: 12 months
Population: Castrate Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GTx- 758 1000mg | Number of Participants Who Are Castrate by Day 60 and Maintained Castrate Range From Day 60 to Day 360/End of Study. | 0 Participants |
| GTx-758 2000mg | Number of Participants Who Are Castrate by Day 60 and Maintained Castrate Range From Day 60 to Day 360/End of Study. | 3 Participants |
| Lupron Depot | Number of Participants Who Are Castrate by Day 60 and Maintained Castrate Range From Day 60 to Day 360/End of Study. | 9 Participants |
Secondary
Time to Castration in Participants With Prostate Cancer
Median time to castration was summarized using the Kaplan-Meier method.
Time frame: 60 days
Population: Per-Protocol Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GTx- 758 1000mg | Time to Castration in Participants With Prostate Cancer | 29 days |
| GTx-758 2000mg | Time to Castration in Participants With Prostate Cancer | 21 days |
| Lupron Depot | Time to Castration in Participants With Prostate Cancer | 21 days |