An Efficacy and Safety Study of JNJ56021927 (ARN509) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS

Phase 1

• Conditions: High- or very-high risk, localized or locally advanced prostate cancer; MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-003007-38-IT
• Lead Sponsor: JANSSEN CILAG INTERNATIONAL NV

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-06-17
• Last Update Posted: 17 August 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Male
• Target Recruitment: 1500

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: aspartate aminotransferase (AST), alanine aminotransferase (ALT), <2 * within limit of normal (ULN).
- total bilirubin WNL
- Serum Creatinine <1.5 mg / dL (<133 µmol / L)
- Platelets> = 140,000 / µL, independent of transfusion and / or growth factors within 3 months before randomization
- Hemoglobin> = 12.0 g / dL (7.4 mmol), independent of transfusion and / or growth factors within 3 months before 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 distal metastases (clinical stage M1). Pelvic nodal disease isolated under the iliac bifurcation (clinical
stage N1) is not an exclusion. The diagnosis of distal metastases (clinical M stage; M0 versus M1a, M1b, M1c) and
pelvic nodal disease (clinical N stage; N1 versus N0) will be assessed by central radiological examination. Patients
are considered eligible only if the central radiological examination confirms the 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, prostatectomy, cryotherapy) treatment for prostate cancer
- History of seizure or any other 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 for prostate cancer (cyproterone acetate included)
- 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 is 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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 <br>- To determine if JNJ-56021927 plus GnRH agonist in subjects with highrisk, localized or locally advanced prostate cancer receiving primary RT<br>results in an improvement of:<br>-- Time to local-regional recurrence<br>-- Time to castration-resistant prostate cancer (CRPC)<br>-- Time to distant metastasis<br>-- Overall survival (OS);Primary end point(s): Metastasis-free survival;Timepoint(s) of evaluation of this end point: 72 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)

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Time to Local-regional Recurrence<br>- Time to Castration-resistant Prostate Cancer (CRPC)<br>- Time to Distant Metastasis<br>- overall survival (OS);Timepoint(s) of evaluation of this end point: - 72 months<br>- 72 months<br>- 72 months<br>- 72 months<br>