Patients with high-risk nonmetastatic prostate cancer progressing after definitive therapy (radical prostatectomy or radiotherapy or both). MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Medivation, Inc., a wholly owned subsidiary of Pfizer Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Age 18 years or older and willing and able to provide informed consent. 2. Histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy, without neuroendocrine differentiation, signet cell, or small cell features. 3. Prostate cancer initially treated by radical prostatectomy or radiotherapy (including brachytherapy) or both, with curative intent. Prostate cryoablation is not considered definitive therapy for this study, but its prior use is not exclusionary. 4. PSA doubling time = 9 months as calculated by the sponsor. 5. Screening PSA by the central laboratory = 1 ng/mL for patients who had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and at least 2 ng/mL above the nadir for patients who had radiotherapy only as primary treatment for prostate cancer. 6. Serum testosterone = 150 ng/dL (5.2 nmol/L) at screening. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening. 8. Estimated life expectancy of = 12 months. 9. Able to swallow the study drug and comply with study requirements. 10. Throughout study, the patient and his female partner who is of childbearing potential must use 2 acceptable methods of birth control (1 of which must include a condom as a barrier method of contraception) from screening through 3 months after the last dose of study drug or per local guidelines where these require additional description of contraceptive methods. Two acceptable methods of birth control thus include the following: ? Condom (barrier method is required) AND ? One of the following is required: – Established and ongoing use of oral, injected, or implanted hormonal method of contraception by the female partner – Placement of an intrauterine device or intrauterine system by the female partner – Additional barrier method including contraceptive sponge and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository by the female partner – Tubal ligation in the female partner performed at least 6 months before screening – Vasectomy or other procedure resulting in infertility (eg, bilateral orchiectomy), performed at least 6 months before screening 11. Throughout the study, the patient must use a condom if having sex with a pregnant woman. 12. Must agree not to donate sperm from first dose of study drug through 3 months after the last dose of study drug. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 262 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 806
Exclusion criteria
Exclusion criteria: 1. Prior or present evidence of distant metastatic disease as assessed by computed tomography (CT) or magnetic resonance imaging (MRI) or chest x-ray for soft tissue disease and whole-body radionuclide bone scan for bone disease. Patients with soft tissue pelvic disease may be eligible if the short axis of the largest lymph node is 2 mg/dL (177 µmol/L) at screening. 15. Albumin < 3.0 g/dL (30 g/L) at screening. 16. History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke or significant brain trauma). History of loss of consciousness (unless of cardiac origin) or transient ischemic attack within 12 months before randomization 17. Clinically significant cardiovascular disease including the following: - Myocardial infarction within 6 months before screening - Unstable angina within 3 months before screening - New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy, as measured by metastasis-free survival (MFS);Secondary Objective: ? To evaluate efficacy, as measured by the secondary and exploratory endpoints;Primary end point(s): Metastasis free survival (MFS) between enzalutamide plus leuprolide and placebo plus leuprolide.;Timepoint(s) of evaluation of this end point: MFS is defined as the duration of time in months between randomization and the earliest objective evidence of radiographic progression by central imaging or death on study (death within 168 days after permanent treatment discontinuation), whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To evaluate efficacy, as measured by the following: * MFS between enzalutamide monotherapy versus placebo plus leuprolide. * Time to prostate-specific antigen (PSA) progression; * Time to first use of new antineoplastic therapy; * Overall survival Other Secondary Endpoints: * Time to distant metastasis * Proportion of patients per group who remain treatment-free 2 years after suspension of study drug treatment at week 37 due to undetectable * Proportion of patients per group with undetectable PSA 2 years after suspension of study drug treatment at week 37 due to undetectable PSA *Proportion of patients per group with undetectable PSA at 36 weeks on study drug *Time to resumption of any hormonal therapy following suspension at week 37 due to undetectable PSA *Time to castration resistance *Time to symptomatic progression *Time to first symptomatic skeletal event *Time to clinically relevant pain *Quality of life *Safety;Timepoint(s) of evaluation of this end point: ?Overall survival: is defined as the time between randomization and death of any cause. Long term follow up data (survival status, skeletal related events and new prostate cancer therapies) will be collected every 12 weeks up until the final analysis of OS. ? Proportion of patients who remain treatment-free 2 years after suspension of study drug treatment at week 37 due to undetectable PSA: no specific timepoint ? Time to castration resistance: the time from randomization to the date of the first PSA increase while on study drug treatment that is = 25% and = 2 µg/L (2 ng/mL) above the nadir or screening value, whichever is lower, and that is confirmed by a second consecutive value obtained at least 3 weeks later. | — |
Countries
Australia, Austria, Brazil, Canada, Denmark, Finland, France, Germany, Italy, Korea, Republic of, Netherlands, Poland, Slovakia, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer, Inc.
Outcome results
None listed