An international study to evaluate the safety and effectiveness of enzalutamide plus leuprolide, enzalutamide alone, and leuprolide alone in men with high-risk nonmetastatic prostate cancer progressing after definitive therapy.
- Conditions
- Patients with high-risk nonmetastatic prostate cancer progressing after definitive therapy (radical prostatectomy or radiotherapy or both).MedDRA version: 20.0Level: PTClassification code 10060862Term: Prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-001634-28-SK
- Lead Sponsor
- Medivation, Inc., a wholly owned subsidiary of Pfizer Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 1068
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
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 < 20 mm for lymph nodes below aortic bifurcation. If the screening bone scan shows a lesion suggestive of metastatic disease, the patient will be eligible only if a second imaging modality (plain film, CT, MRI) does not show bone metastasis. If the imaging results are equivocal or consistent with metastasis by central radiology review, the patient is not eligible for enrollment. Positron-emission tomography (PET) is not an evaluable imaging modality for this study.
2. Prior hormonal therapy.Neoadjuvant/adjuvant therapy to treat prostate cancer = 36 months in duration and = 9 months before randomization, or a single dose or a short course (= 6 months) of hormonal therapy given for rising PSA = 9 months before randomization is allowed.
3. Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for prostate cancer.
4. Prior systemic biologic therapy, including immunotherapy,for prostate cancer.
5. Major surgery within 4 weeks before randomization date.
6. Treatment with 5-a reductase inhibitors (finasteride, dutasteride) within 4 weeks of randomization.
7. For patients who had a prior prostatectomy,a suitable candidate for salvage radiotherapy as determined by the investigator in consideration of appropriate guidelines (eg,American Society for Radiation Oncology/American Urological Association[ASTRO/AUA]; European Association of Urology [EAU]).
8. Participation in a clinical study of an investigational agent that inhibits the androgen receptor or androgen synthesis (eg,TAK-700, ARN-509, ODM-201); patients who received placebo are allowed.
9. Use of any other investigational agent within 4 weeks before randomization date.
10. Known or suspected brain metastasis or active leptomeningeal disease.
11. History of another invasive cancer within 3 years before screening, with the exception of fully treated cancers with a remote probability of recurrence. The medical monitor and investigator must agree that the possibility of recurrence is remote.
12. Absolute neutrophil count <1500/µL, platelet count <100,000/µL,or hemoglobin <10 g/dL (6.2 mmol/L) at screening. NOTE: May not have received any growth factors or blood transfusions within 7 days before the hematology values obtained at screening.
13. Total bilirubin (TBili) =1.5-times the upper limit of normal (except patients with documented Gilbert’s disease), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 2.5-times the upper limit of normal at screening.
14. Creatinine > 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 II
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate efficacy, as measured by metastasis-free survival (MFS);Secondary Objective: ? To evaluate efficacy, as measured by the secondary and exploratory<br>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 Outcome Measures
Name Time Method