High-risk localized or locally advanced prostate cancer MedDRA version: 20.0 Level: PT Classification code 10060862 Term: Prostate cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Must be =18 years of age 2. Signed an informed consent form (ICF) indicating that the subject understands the purpose of and procedures required for the study and is willing to participate in the study; subjects must be willing and able to adhere to the prohibitions and restrictions specified in this protocol (Section 4.3) 3. Histologically confirmed adenocarcinoma of the prostate 4. Criterion modified per Amendment 1 4.1. Criterion modified per Amendment 2 4.2 High risk disease defined by a total Gleason Sum Score =4+3 (=Grade Groups [GG] 3 5) and =1 of the following 4 criteria: • Any combination of Gleason Score 4+3 (=GG 3) and Gleason Score 8 (4+4 or 5+3) in =6 systematic cores (with =1 core Gleason Score 8 [4+4 or 5+3] included); • Any combination of Gleason Score 4+3 (=GG 3) and Gleason Score 8 (4+4 or 5+3) in =3 systematic cores and PSA =20 ng/mL (with =1 core Gleason Score 8 [4+4 or 5+3] included); • Gleason Score =9 (=GG 5) in at least 1 systematic or targeted core; or • At least 2 systematic or targeted cores with continuous Gleason Score =8 (=GG 4), each with =80% involvement 5. Criterion modified per Amendment 1 5.1. Candidate for RPLND as per the investigator 6. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 7. Criterion modified per Amendment 1 7.1. Criterion modified per Amendment 2 7.2. Adequate organ function determined by the following central laboratory values: a. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin within normal limits, ie, = the upper limit of normal ([ULN]; note that in subjects with Gilbert’s syndrome, if total bilirubin is >1.5 X ULN, measure direct and indirect bilirubin. If direct bilirubin is =1.5 X ULN, the subject may be eligible); b. Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 300
Exclusion criteria
Exclusion criteria: 1. Distant metastasis based on conventional imaging (clinical stage M1). 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 2. Criterion modified per Amendment 2 2.1. (a) Prior treatment with androgen receptor antagonists. (b) Treatment with GnRH analogs prior to ICF signature. 3. Criterion deleted per Amendment 1 4. Criterion deleted per Amendment 1 5. Bilateral orchiectomy 6. Criterion modified per Amendment 1 6.1. Criterion modified per Amendment 2 6.2. History of prior systemic or local therapy for prostate cancer, including pelvic radiation for prostate cancer 7. Criterion modified per Amendment 1 7.1. Use of any investigational agent =4 weeks prior to randomization or any therapeutic procedure for prostate cancer at any time 8. Major surgery =4 weeks prior to randomization 9. Any of the following within 6 months prior to first dose of study drug: severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (eg, pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias or New York Heart Association Class II to IV heart disease; uncomplicated deep vein thrombosis is not considered exclusionary 10. Human immunodeficiency virus-positive subjects with 1 or more of the following: a. Not receiving highly active antiretroviral therapy b. Had a change in antiretroviral therapy within 6 months of the start of screening c. Receiving antiretroviral therapy that may interfere with study drug (consult sponsor for review of medication prior to enrollment) d. CD4 count <350 at screening e. AIDS-defining opportunistic infection within 6 months of start of screening 11. Active or symptomatic viral hepatitis or chronic liver disease; ascites or bleeding disorders secondary to hepatic dysfunction 12. Criterion modified per Amendment 2 12.1. History of seizure; 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); presence of brain arteriovenous malformation; or intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect 13. Treatment with drugs known to lower the seizure threshold within 4 weeks prior to randomization 14. Gastrointestinal conditions affecting absorption 15. Criterion modified per Amendment 1 15.1. Known or suspected contraindications or hypersensitivity to apalutamide, GnRHa analogues or any of the components of the formulations 16. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject 17. Criterion modified per Amendment 2 17.1. Active malignancies (ie, progressing or requiring treatment or treatment change in the last 24 months) other than prostate cancer. The only allowed exceptions are: non-muscle invasive bladder cancer (NMIBC); skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured; breast cancer (adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of loca
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine if treatment with apalutamide plus ADT before and after RPLND in subjects with high-risk localized or locally advanced prostate cancer results in an improvement in pCR rate and MFS based on conventional imaging, as compared to placebo plus ADT. ;Secondary Objective: - To determine if treatment with apalutamide plus ADT before and after RPLND in subjects with high risk localized or locally advanced prostate cancer results in improvement of other efficacy endpoints, as compared to placebo plus ADT. - To characterize the safety profile of treatment with apalutamide plus ADT before and after RPLND in subjects with high risk localized or locally advanced prostate cancer.;Primary end point(s): - pCR rate (as defined in the pathology charter and assessed by a pathology blinded independent central review [BICR]) - MFS (evaluated by radiology BICR on conventional imaging [ie, computed tomography (CT)/magnetic resonance imaging (MRI) and bone scan]) ;Timepoint(s) of evaluation of this end point: - at radical prostatectomy - until documented distant metastasis, death, lost to follow-up, withdrawal of consent, or termination of the study by the sponsor, whichever occurs first | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Prostate-specific antigen (PSA)-free survival - Progression-free survival (PFS) (evaluated by radiology BICR on conventional imaging) - Adverse events (AEs), vital signs measurements, physical examinations, clinical laboratory tests, and treatment compliance. ;Timepoint(s) of evaluation of this end point: - the time from randomization to the first detectable serum PSA level with recovered testosterone levels after undetectable PSA post-radical prostatectomy with lymph node dissection (RPLND) or death, whichever occurs first - time from randomization to first documentation of BICR-confirmed radiographic progressive disease or death due to any cause (whichever occurs first) + 1 day - from signing of consent until 30 days after last dose of study drug. Clinical Labs & compliance per T&E on treatment | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Russian Federation, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed