An Efficacy and Safety Study of JNJ-56021927 (ARN-509) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS

• Register: EUCTR
• Last refreshed on: 16 May 2022
• Main ID: EUCTR2015-003007-38-DE
• Date of registration: 06/11/2015
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: An Efficacy and Safety Study of JNJ-56021927 (ARN-509) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS
• Scientific title: A Randomized, Double-blind, Placebo-controlled Phase 3 Study of JNJ-56021927 in Subjects with High-risk, Localized or Locally Advanced Prostate Cancer Receiving Treatment with Primary Radiation Therapy
• Date of first enrolment: 04/02/2016
• Target sample size: 1500
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003007-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Belgium, Brazil, Bulgaria, Canada, China, Czech Republic, Czechia, France, Germany, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Netherlands, Poland, Romania, Russian Federation, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV (Janssen Biologics BV)

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV (Janssen Biologics BV)

Key inclusion & exclusion criteria

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 stage per AJCC 8th Edition,
2) Gleason score 7, PSA >=20 nanogram per mililiters (ng/mL), and >=cT2c stage per AJCC 8th Edition
- Charlson comorbidity index (CCI) <=3
- An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) grade of 0 or 1
- Adequate organ function determined by the following central laboratory values:
1) aspartate aminotransferase (AST), alanine aminotransferase (ALT) within normal limits (WNL)
2) total bilirubin WNL
3) Serum creatinine <1.5 mg/dL (<133 µmol/L)
4) Platelets =140,000/µL, independent of transfusion and/or growth factors within 3 months prior to randomization
5) Hemoglobin = 12.0 g/dL (7.4 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
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 900
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 600

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 GnRH analogue or antiandrogen or both for >3 months prior to randomization
- Bilateral orchiectomy
- History of pelvic radiation
- Prior systemic (eg, chemotherapy) or local (eg, 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 (eg, strontium 89) or immunotherapy (eg, sipuleucel-T) for prostate cancer
- Prior treatment with systemic glucocorticoids =4 weeks prior to randomization or subject expected to require long-term use of corticosteroids during the study
- Use of 5-alpha reductase inhibitors (eg, 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 antiepileptic 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


Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

High- or very-high risk, localized or locally advanced prostate cancer
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)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Code: JNJ-56021927
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Not assigned
CAS Number: 956104-40-8
Current Sponsor code: JNJ-56021927
Other descriptive name: JNJ-56021927-AAA
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 60-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Trade Name: Bicalutamid-Actavis
Product Name: Bicalutamid
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BICALUTAMIDE
CAS Number: 90357-06-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: approximately 84 months

Main Objective: To determine if apalutamide plus gonadotropin releasing hormone (GnRH) agonist in subjects with high-risk, localized or locally advanced prostate cancer receiving primary radiation therapy (RT) results in an improvement of metastasis-free survival (MFS) evaluated by blinded independent central review (BICR)

Primary end point(s): Metastasis-free survival

Secondary Objective: - To characterize the safety profile of apalutamide plus GnRH agonist in subjects with high-risk, localized or locally advanced prostate cancer receiving primary RT
- To determine if apalutamide plus GnRH agonist in subjects with high-risk, localized or locally advanced prostate cancer receiving primary RT results in an improvement of:
* Event-free survival
* Time to PSA progression
* Overall survival (OS)
* Time to distant metastasis
* Time to next local or systemic treatment
* MFS by conventional or positron emission tomography (PET) imaging

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: approximately 84 months

Secondary end point(s): - Event-free survival
- Time to PSA progression
- Overall Survival (OS)

Secondary ID(s)

2015-003007-38-GB

56021927PCR3003

Source(s) of Monetary Support

Janssen-Cilag International NV

Ethics review

Status: Approved
Approval date: 22/12/2015
Contact: