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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
Prostatic Neoplasms	Drug: Apalutamide; Drug: Bicalutamide; Drug: Bicalutamide Placebo; Drug: Apalutamide Placebo; Drug: GnRH (agonist); Radiation: 74-80 Grays (units of radiation)	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	1499 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	ATLAS: 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
Actual Study Start Date :	November 19, 2015
Estimated Primary Completion Date :	December 30, 2022
Estimated Study Completion Date :	October 6, 2026

Arms and Interventions

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Arm	Intervention/treatment
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)

Outcome Measures

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Primary Outcome Measures :

1. Metastasis-free survival [ Time Frame: 84 Months ]

Secondary Outcome Measures :

1. Time to Local-regional Recurrence [ Time Frame: 84 Months ]
2. Time to Castration-resistant Prostate Cancer (CRPC) [ Time Frame: 84 Months ]
3. Time to Distant Metastasis [ Time Frame: 84 Months ]
4. Overall Survival (OS) [ Time Frame: 84 Months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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, 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

Contacts and Locations

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Sponsors and Collaborators

Aragon Pharmaceuticals, Inc.

Investigators

Study Director:	Aragon Pharmaceuticals, Inc. Clinical Trial	Aragon Pharmaceuticals, Inc.

More Information

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Additional Information:

To learn how to participate in this trial please click here. 

Responsible Party:	Aragon Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT02531516 History of Changes
Other Study ID Numbers:	CR106935; 56021927PCR3003 ( Other Identifier: Aragon Pharmaceuticals, Inc. ); 2015-003007-38 ( EudraCT Number )
First Posted:	August 24, 2015
Last Update Posted:	November 16, 2018
Last Verified:	November 2018

Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Aragon Pharmaceuticals, Inc.:

Prostatic neoplasms; Prostate Cancer; High-Risk prostate cancer; JNJ-56021927; Apalutamide	ATLAS; Radiation; Long-term hormone therapy; Localized or locally advanced prostate cancer; Janssen

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases	Hormones; Bicalutamide; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Androgen Antagonists; Hormone Antagonists; Antineoplastic Agents