The purpose of this study is to evaluate the efficacy and safety of MDV3100, a novel potent androgen-receptor antagonist without known agonist activity, in asymptomatic or mildly symptomatic patients with progressive metastatic prostate cancer who…
ID
Source
Brief title
Condition
- Reproductive neoplasms male malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Co-Primary Objectives
• To determine the benefit of MDV3100 as compared to placebo as assessed by
overall survival;
• To determine the benefit of MDV3100 as compared to placebo as assessed by
radiographic progression-free survival (rPFS).
Secondary outcome
Key Secondary Objectives
• To determine the benefit of MDV3100 as compared to placebo as assessed by
time to first skeletal-related event;
• To determine the benefit of MDV3100 as compared to placebo as assessed by
time to initiation of cytotoxic chemotherapy.
Background summary
Worldwide, prostate cancer ranks third in cancer incidence and sixth in cancer
mortality in men. Prostate cancer growth is dependent on androgens, and
depleting or blocking androgen action has been a mainstay of treatment for over
6 decades. Despite the early sensitivity of tumors to hormonal strategies,
tumors that progress despite androgen deprivation generally represent a
transition to the lethal variant of the illness. Once patients progress on
docetaxel, there is currently no approved second line therapy and most patients
ultimately succumb to this disease.
Because overexpression of the androgen receptor is a common feature of
progressive prostate cancer, second generation anti-androgen therapies that are
more potent and that are pure antagonists may be effective in such patients.
Study objective
The purpose of this study is to evaluate the efficacy and safety of MDV3100, a
novel potent androgen-receptor antagonist without known agonist activity, in
asymptomatic or mildly symptomatic patients with progressive metastatic
prostate cancer who have disease progression despite androgen deprivation
therapy.
Study design
The PREVAIL study is a multinational Phase 3, randomized, double-blind,
placebo-controlled efficacy and safety study of oral MDV3100 (160 mg/day) in
asymptomatic or mildly symptomatic patients with progressive metastatic
prostate cancer who have disease progression despite androgen deprivation
therapy. Patients must not have been previously treated with cytotoxic
chemotherapy. Approximately 1,680 patients will be centrally randomized 1:1.
Randomization will be stratified by investigative site.
Intervention
Study drug therapy (MDV3100 or placebo) is given as four oral capsules taken as
one dose per day. Study drug therapy should be continued as long as the
patient is tolerating the study drug and continues androgen deprivation therapy
(i.e., surgical castration or ongoing gonadotropin GnRH-analogue therapy) until
confirmed radiographic disease progression or a skeletal related event AND one
of the two following events: 1) initiation of cytotoxic chemotherapy; or 2)
initiation of an investigational agent for treatment of prostate cancer If
another non-cytotoxic systemic anti-neoplastic agent is initiated, study drug
therapy may be continued per the Investigator*s clinical judgment as long as
the patient is tolerating the study drug and continues androgen deprivation
therapy. Radiation therapy, vaccine therapy, and initiation of bisphosphonates
or other approved bone targeting agents, and standard of care steroid and pain
management are allowed and should not result in discontinuation of study drug
therapy. Study drug should be discontinued prior to initiation of a cytotoxic
chemotherapy or another investigational agent.
Study burden and risks
A discussion was presented in section E9 of this document.
Medivation Inc., 36th Floor, 525 Market Street -
San Francisco, California, CA 94105
US
Medivation Inc., 36th Floor, 525 Market Street -
San Francisco, California, CA 94105
US
Listed location countries
Age
Inclusion criteria
The inclusion criteria apply to patients receiving enzalutamide or placebo during double-blind treatment.
Eligible patients must meet all inclusion criteria.;1. Received randomized double-blind treatment in PREVAIL;
2. Open-label day 1 visit is within 6 months after this amendment is approved and becomes effective at the study site;
3. Is willing to maintain androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist or has had a bilateral orchiectomy;
4. Is able to swallow enzalutamide capsules whole and to comply with study requirements throughout the study.
Exclusion criteria
The exclusion criteria apply only to patients starting new treatment with enzalutamide after receiving placebo as randomized treatment. Each patient must NOT meet any of the following criteria:
1. Is taking commercially available enzalutamide (Xtandi);
2. Has any clinically significant cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, hepatic, infectious, metabolic, neurologic, psychological, pulmonary, or renal disorder or any other condition, including excessive alcohol or drug abuse, or secondary malignancy, that may interfere with study participation in the opinion of the investigator or medical monitor;
3. Has current or previously treated brain metastasis or active leptomeningeal disease;
4. Has a history of seizure or a condition that may increase the risk of seizure;
5. Has total bilirubin >= 1.5-times the upper limit of normal (ULN) (except patients with a diagnosis of Gilbert*s disease); alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >= 2.5-times ULN at screening. For patients with documented liver metastases, ALT and AST exclusion is > 5-times ULN;
6. Has creatinine > 2 mg/dL (177 µmol/L) at screening.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-020821-41-NL |
| ClinicalTrials.gov | NCT01212991 |
| CCMO | NL33544.091.10 |