Purpose

The purpose of this study is to determine if apalutamide plus gonadotropin releasing hormone (GnRH) agonist in participants with high-risk, localized or locally advanced prostate cancer receiving primary radiation therapy results in an improvement of metastasis-free survival.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age >= 18 years
  • Indicated and planned to receive primary radiation therapy for prostate cancer
  • Histologically confirmed adenocarcinoma of an intact prostate, and 1 of the following at diagnosis: 1) Gleason score >=8 and >=cT2c, 2) Gleason score >=7, PSA >=20 nanogram per milliliters (ng/mL), and >=cT2c
  • Charlson index (CCI) <=3
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade of 0 or 1
  • Adequate organ function: (1) aspartate aminotransferase (AST), alanine aminotransferase (ALT), within normal limits (WNL), (2) serum creatinine less than (<) 1.5 milligram/deciliter (mg/dL) (<133 micromoles/Liter [mcmol/L]), (3) platelets greater than or equal to (>=)140,000/microLiter (mcL), independent of transfusion and/or growth factors within 3 months prior to randomization, (4) Hemoglobin >= 12.0 gram/deciliter (g/dL) (7.4 millimloes [mmol], independent of transfusion and/or growth factors within 3 months prior to randomization
  • Participants who are sexually active (even men with vasectomies) and willing to use a condom and agree not to donate sperm during the trial
  • Signed, written, informed consent
  • Be able to swallow whole study drug tablets

Exclusion Criteria

  • Presence of distant metastasis, (clinical stage M1). Isolated pelvic nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion. Diagnosis of distant metastasis (clinical M stage; M0 versus M1a, M1b, M1c) and pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological review. Patients are considered eligible only if the central radiological review confirms clinical stage M0.
  • Prior treatment with gonadotropin releasing hormone (GnRH) analogue or anti-androgen or both for >3 months prior to randomization
  • Bilateral orchiectomy
  • History of pelvic radiation
  • Prior systemic (example [e.g.], chemotherapy) or local (e.g. radical prostatectomy, cryotherapy) treatment for prostate cancer
  • History of seizure or any condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness <= 1 year prior to randomization; brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect)
  • Prior treatment with enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents (including cyproterone acetate) for prostate cancer
  • Prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy (e.g., sipuleucel-T) for prostate cancer
  • Prior treatment with systemic glucocorticoids ≤4 weeks prior to randomization or is expected to require long-term use of corticosteroids during the study
  • Use of 5-alpha reductase inhibitors (e.g., dutasteride, finasteride) <=4 weeks prior to randomization
  • Use of any investigational agent <=4 weeks prior to randomization
  • Current chronic use of opioid analgesics for >=3 weeks for oral or >7 days for non-oral formulations
  • Major surgery <=4 weeks prior to randomization
  • Current or prior treatment with anti-epileptic medications for the treatment of seizures
  • Gastrointestinal conditions affecting absorption
  • Known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide or GnRH agonists or any of the components of the formulations
  • Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Apalutamide
Participants will receive apalutamide (240 mg), by mouth, once daily for overall 30 months, plus bicalutamide placebo, by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.
  • Drug: Apalutamide
  • Drug: Bicalutamide Placebo
  • Drug: GnRH (agonist)
  • Radiation: 74-80 Grays (units of radiation)
Active Comparator
Control group
Participants will receive apalutamide placebo, by mouth, once daily for overall 30 months, plus bicalutamide (50 mg), by mouth, once daily, for four months from randomization. All participants are treated with gonadotropin releasing hormone (GnRH) agonist for 30 months from randomization and radiation therapy to the prostate started at about 8 weeks after randomization.
  • Drug: Bicalutamide
  • Drug: Apalutamide Placebo
  • Drug: GnRH (agonist)
  • Radiation: 74-80 Grays (units of radiation)

More Details

NCT ID
NCT02531516
Status
Active, not recruiting
Sponsor
Aragon Pharmaceuticals, Inc.

Study Contact

Detailed Description

This is a randomized, double-blind, placebo-controlled, multicenter study of apalutamide plus GnRH agonist compared with GnRH agonist among participants with high-risk, localized or locally advanced prostate cancer receiving primary radiation therapy (RT). The study will include a Screening Phase, Treatment Phase, a Posttreatment Phase, and a Long-term Follow-up Phase. Participants will either receive either apalutamide (experimental) or bicalutamide 50 milligram (mg) capsule plus placebo as control group. Safety will be monitored throughout the study.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.