ATLAS: A Randomized, Double-blind, Placebo-controlled Phase III Study of JNJ-56021927 in Subjects With High-risk, Localized or Locally Advanced Prostate Cancer Receiving Treatment With Primary Radiation Therapy
Study Identifier:
56021927PCR3003
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruitment Complete
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Study Summary
To determine if JNJ-56021927 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 (MFS) evaluated by blinded independent central review (BICR) To evaluate the efficacy of apalutamide in patients with high-risk localized or locally advanced prostate cancer (Gleason score of > or = 8 and > or = cT2c or a Gleason score of > or = 7 and prostate-specific antigen > or = 20 ng/mL and > or = cT2c) receiving primary RT. Imaging with CT or MRI and bone scan will be conducted at baseline and then every 6 months following biochemical failure until documented distant metastasis by blinded-to-arm independent central review or death. To investigate whether treatment intensification with the addition of APA to neoadjuvant and adjuvant treatment with gonadotropin-releasing hormone agonist (GnRHa) and external beam radiation therapy (EBRT) will improve metastasis-free survival (MFS) in high-risk pts. To determine MFS improvement, long-term patient retention and physician engagement are critical
The primary objective was to determine whether apalutamide in combination with a gonadotropin-releasing hormone (GnRH) agonist could prolong metastasis-free survival (MFS) based on conventional imaging or prostate-specific membrane antigen (PSMA)-positron emission tomography (PET) in high-risk patients with radiotherapy-initiated (RT) prophylaxis (assessed by a blinded Independent Central Review Committee [BICR]). Secondary objectives included the safety profile of JNJ-56021927 in combination with a gonadotropin-releasing hormone agonist in high-risk patients with RT prophylaxis, including event-free survival, time to PSA progression, BICR-confirmed MFS, NED, and OS based on conventional imaging, time to distant metastasis, time to next local or systemic therapy, and BICR-confirmed event-free survival based on conventional imaging.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Prostate
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
Phase III
Sex
Male
Age
18+ years
Study Drug
Drug: Arms:
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Drug: The study will include a Screening Phase, Treatment Phase, a Posttreatment Phase, and a Long-term Follow-up Phase. Participants will either receive either JNJ-56021927 (experimental) or bicalutamide 50 milligram (mg) capsule plus placebo as control group. Safety will be monitored throughout the study.
Drug: ASCO 2016:
Drug: Study Design - Study Sequence
Drug: Treatment phase:
Drug: Follow-up Phase
Drug: ESMO 2016:
Drug: 2022 ASCO:
Drug: experimental drug
Study Status
Indicates the current recruitment status or the expanded access status
Recruitment Complete
Requirements information
Inclusion criteria
- Age > or = 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 > or =8 and > or =cT2c, 2) Gleason score > or =7, PSA > or =20 nanogram per milliliters (ng/mL), and > or =cT2c Charlson index (CCI) < or =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 (> or =)140,000/microLiter (mcL), independent of transfusion and/or growth factors within 3 months prior to randomization, (4) Hemoglobin > or = 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
- CFDA:
- 1Participants must be male and 18 years of age or older.2Each participant must sign an ICF (Initial Clinical Filing Form) indicating their understanding of the study's purpose and required procedures and their willingness to participate. Participants must be willing and able to comply with the contraindications or restrictions specified in the study protocol.3Prostate cancer patients who are suitable for and plan to receive RT as initial treatment4According to the revised criteria (Revised 1): Histologically confirmed (intact) prostate adenocarcinoma, meeting one of the following criteria at diagnosis: Gleason score ≥8 and ≥AJCC cT2c stage (according to AJCC 8th edition); Gleason score 7, PSA ≥20 ng/mL and ≥AJCC cT2c stage (according to AJCC 8th edition). Note: Clinical T stage (cT2c, cT3, cT4) should be recorded using any acceptable clinical T stage assessment results, including physical examination (DRE), transrectal ultrasound, CT, or MRI.5Charlson Comorbidity Index (CCI) ≤36ECOG PS is level 0 or 1.7According to the revised criteria (Revised 1): Adequate organ function is determined based on the following central laboratory values: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) within the normal range (WNL); total bilirubin within the normal range (WNL); serum creatinine <1.5 mg/dL (<133 μmol/L); platelet count ≥140,000/L, with no blood transfusion and/or growth factor infusion within 3 months prior to randomization; hemoglobin ≥12.0 g/dL (7.4 mmol/L), with no blood transfusion and/or growth factor infusion within 3 months prior to randomization.8To minimize the risk of drug exposure from ejaculation (even in patients who have undergone vasectomy), subjects must use condoms during sexual intercourse while taking the medication and for three months after the last dose of the study drug. Sperm donation is not permitted during treatment or for three months after the last dose of the study drug.9Able to swallow an entire research drug
Exclusion criteria
- Presence of distant metastasis, including pelvic nodal disease below the iliac bifurcation >2 cm in the short axis 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 procedural (e.g., prostatectomy, cryotherapy) treatment for prostate cancer History of seizure or condition that may predispose to seizure (including, but not limited to prior stroke, transient ischemic attack or loss of consciousness < or = 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 Prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy (e.g., sipuleucel-T) for prostate cancer Prior treatment with systemic glucocorticoids < or =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) < or =4 weeks prior to randomization Use of any investigational agent < or =4 weeks prior to randomization Current chronic use of opioid analgesics for >or =3 weeks for oral or >7 days for non-oral formulations Major surgery < or =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 JNJ-56021927, 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
- CFDA:
- 1Distant metastasis is present (clinical stage M1). Isolated pelvic nodular lesions below the bifurcation of the common iliac artery (clinical stage N1) are not considered exclusion criteria. The diagnosis of distant metastasis (clinical stage M; M0 vs. M1a, M1b, M1c) and pelvic nodular lesions (clinical stage N; N1 vs. N0) is assessed by central radiological review. A patient is considered eligible only if the central radiological review confirms a clinical stage of M0.2Prior to randomization, the patient had received GnRH analogs or anti-androgens, or both, for more than 3 months.3Bilateral orchiectomy4History of pelvic radiotherapy5Previously received systemic (e.g., chemotherapy) or local (e.g., radical prostatectomy, cryotherapy) treatment for prostate cancer.6Enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogen, megestrol acetate, and progestin drugs (including cyproterone acetate) have been used to treat prostate cancer.7Prostate cancer has previously been treated with radiopharmaceuticals (e.g., strontium-89) or immunotherapy (e.g., sipuleucel-T).8Subjects who have received systemic treatment with glucocorticoids within 4 weeks prior to randomization or who are expected to require long-term use of corticosteroids during the study period.9Patients who used 5-α reductase inhibitors (e.g., dutasteride, finasteride) within 4 weeks prior to randomization.10Anyone who has used any investigational drug within the 4 weeks prior to randomization11Currently, patients are on long-term use of oral opioid analgesics for ≥3 weeks or non-oral preparations for ≥7 days.12Those who underwent major surgery within the previous 4 weeks before being randomly assigned to a group13A history of epileptic seizures or any other predisposing condition for epilepsy (including but not limited to stroke, transient ischemic attack or loss of consciousness within 1 year prior to randomization; arteriovenous malformation; intracranial tumors that cause cerebral edema or mass effect, such as schwannomas or meningiomas).14Have you currently or previously used antiepileptic drugs to treat epileptic seizures?15Suffering from gastrointestinal diseases that affect absorption16There is a known or suspected contraindication or hypersensitivity to apalutamide, bicalutamide, or GnRH agonists, or any of the ingredients in these formulations.17There exists a situation where researchers believe that participating in the study is not in the best interests of the participants.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Carolinas
Myrtle Beach, SC, United States, 29572
Investigator
Neal Shore
Status
Recruitment Complete
Condition(s) Treated at Site
Prostate