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 (RT) results in an improvement of metastasis-free survival (MFS) based on conventional imaging assessed by blinded independent central review (BICR).
Brief Title
An Efficacy and Safety Study of JNJ-56021927 (Apalutamide) in High-risk Prostate Cancer Subjects Receiving Primary Radiation Therapy: ATLAS
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Prostatic Neoplasms
Eligibility 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
* 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
Inclusion 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
* 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
Gender
Male
Gender Based
false
Keywords
Prostatic neoplasms
Prostate Cancer
High-Risk prostate cancer
JNJ-56021927
Apalutamide
ATLAS
Radiation
Long-term hormone therapy
Localized or locally advanced prostate cancer
Janssen
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02531516
Org Class
Industry
Org Full Name
Aragon Pharmaceuticals, Inc.
Org Study Id
CR106935
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
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 assessed by blinded independent central review (BICR), histopathologic diagnosis of distant metastasis, or death from any cause, whichever occurs first.
Outcome Measure
Metastasis-Free Survival (MFS)
Outcome Time Frame
108 Months
Secondary Ids
Secondary Id
56021927PCR3003
Secondary Id
2015-003007-38
Secondary Id
2023-505246-26-00
Secondary Outcomes
Outcome Description
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 based on conventional imaging assessed by BICR or histopathologic diagnosis, distant metastasis based on conventional imaging assessed by BICR or histopathologic diagnosis, or death.
Outcome Time Frame
108 Months
Outcome Measure
Event-Free Survival (EFS) Based on Conventional Imaging Assessed By BICR
Outcome Description
Time to PSA progression is defined as the time from randomization to the date of PSA nadir plus (+) 0.5 nanograms per milliliter (ng/mL) and rising.
Outcome Time Frame
108 Months
Outcome Measure
Time to PSA Progression
Outcome Description
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 assessed by BICR or PSMA-PET imaging assessed by BICR, histopathologic diagnosis of distant metastasis, or death from any cause, whichever occurs first.
Outcome Time Frame
108 Months
Outcome Measure
MFS Based on Conventional Imaging or Prostate-Specific Membrane Antigen (PSMA)-Positron Emission Tomography (PET) Imaging Assessed by BICR
Outcome Description
NED is defined as: alive; no PSA progression; no distant metastasis based on conventional imaging assessed by BICR or PSMA-PET imaging assessed by BICR or histopathologic diagnosis; no local or regional recurrence based on conventional imaging assessed by BICR or PSMA-PET imaging assessed by BICR, or histopathologic diagnosis; 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).
Outcome Time Frame
108 Months
Outcome Measure
No Evidence of Disease (NED) Based on Conventional Imaging or PSMA PET Imaging Assessed by BICR
Outcome Description
OS is defined as the time from randomization to date of death from any cause.
Outcome Time Frame
108 Months
Outcome Measure
Overall Survival (OS)
Outcome Description
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 based on conventional imaging assessed by BICR or histopathologic diagnosis of distant metastasis.
Outcome Time Frame
108 Months
Outcome Measure
Time to Distant Metastasis Based on Conventional Imaging Assessed by BICR
Outcome Description
EFS is defined as the time from randomization to the date of the first occurrence of PSA failure by the Phoenix definition, local or regional disease recurrence based on conventional imaging assessed by BICR or PSMA-PET imaging assessed by BICR or histopathologic diagnosis, distant metastasis based on conventional imaging assessed by BICR or PSMA-PET imaging assessed by BICR or histopathologic diagnosis, or death.
Outcome Time Frame
108 Months
Outcome Measure
EFS Based on Conventional Imaging or PSMA-PET Imaging Assessed by BICR
Outcome Description
Time to next local or systemic treatment is defined as the time from randomization to the first subsequent therapy, including re-initiation of androgen deprivation therapy (ADT) and local treatments for local-regional recurrence or distant metastasis.
Outcome Time Frame
108 Months
Outcome Measure
Time to Next Local or Systemic Treatment
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Benjamin Gartrell
Investigator Email
bgartrel@montefiore.org
Investigator Phone
718-405-8404