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

Prostatic Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02531516
• Other study ID #: CR106935
• Secondary ID: 56021927PCR30032
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 19, 2015
• Est. completion date: December 29, 2028

Study information

• Verified date: June 2024
• Source: Aragon Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 (RT) results in an improvement of metastasis-free survival based on conventional or prostate specific membrane antigen-positron emission tomography (PSMA-PET) imaging evaluated by blinded independent central review (BICR).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1503
• Est. completion date: December 29, 2028
• Est. primary completion date: June 30, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Prostatic Neoplasms

Intervention

Drug:
• Apalutamide

• Bicalutamide

• Bicalutamide Placebo

• Apalutamide Placebo

• GnRH (agonist)

Radiation:
• 74-80 Grays (units of radiation)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Aragon Pharmaceuticals, Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metastasis-free Survival	Metastasis-free survival is defined as the time from randomization to the date of the first occurrence of radiographic bone or soft tissue distant metastasis based on conventional imaging or prostate specific membrane antigen-positron emission tomography (PSMA-PET) imaging by blinded independent central review (BICR), histopathologic diagnosis of distant metastasis, or death from any cause, whichever occurs first.	108 Months
Secondary	Event-free Survival on Conventional Imaging or PSMA-PET Imaging	Event-free survival is defined as the time from randomization to the date of the first occurrence of prostate specific antigen (PSA) failure by the Phoenix definition, local or regional disease recurrence on conventional imaging or PSMA-PET imaging by BICR or histopathologic diagnosis, distant metastasis on conventional imaging or PSMA-PET imaging by BICR or histopathologic diagnosis, or death.	108 Months
Secondary	Time to Prostate Specific Antigen (PSA) Progression	Time to PSA progression is defined as time from randomization to the date of PSA nadir plus (+) 0.5 nanograms per milliliter (ng/mL) and rising.	108 Months
Secondary	Metastasis-free Survival (MFS) on Conventional Imaging by Blinded Independent Central Review (BICR)	MFS is defined as the time from randomization to the date of the first occurrence of radiographic bone or soft tissue distant metastasis based on conventional imaging by BICR, histopathologic diagnosis of distant metastasis, or death from any cause, whichever occurs first.	108 Months
Secondary	No Evidence of Disease (NED)	NED is defined as: alive; no prostate specific antigen (PSA) progression; no distant metastasis on conventional imaging or PSMA-PET imaging by BICR; no local or regional recurrence on conventional imaging or PSMA-PET imaging by BICR; no subsequent therapy for prostate cancer; testosterone recovery to age-related pre-androgen deprivation therapy (pre-ADT)/baseline or greater than (>) 200 nanogram per deciliter (ng/dL).	108 Months
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to date of death from any cause.	108 Months
Secondary	Time to Distant Metastasis	Time to distant metastasis is defined as the time from randomization to the date of the first occurrence of radiographic or pathological bone or soft tissue distant metastasis on conventional imaging or PSMA-PET imaging by BICR or histopathologic diagnosis of distant metastasis.	108 Months
Secondary	Event-free Survival on Conventional Imaging	EFS is defined as the time from randomization to the date of the first occurrence of prostate specific antigen (PSA) failure by the Phoenix definition, local or regional disease recurrence on conventional imaging by BICR or histopathologic diagnosis, distant metastasis on conventional imaging by BICR or histopathologic diagnosis, or death.	108 Months
Secondary	Time to Next Local or Systemic Treatment	Time to next local or systemic treatment defined as time from randomization to first subsequent therapy, including re-initiation of androgen deprivation therapy (ADT) and local treatments for local-regional recurrence or distant metastasis.	108 Months