Castration-Resistant Prostate Cancer MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: ARN-509
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: Apalutamide
CAS Number: 956104-40-8
Other descriptive name: JNJ-5602127-AAA
Concentration unit: % (W/W) percent weight/wei
Sponsors
Aragon Pharmaceuticals, Inc
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features, with high risk for development of metastases, defined as PSADT = 10 months. PSADT is calculated using 3 PSA values obtained during continuous ADT (see Section 5.1) 2. Castration-resistant prostate cancer demonstrated during continuous ADT, defined as 3 PSA rises at least 1 week apart, with the last PSA > 2 ng/mL 3. Surgically or medically castrated, with testosterone levels of 1.5 x ULN is allowed if Gilbert's disease is documented prior to end of screening procedure -Serum creatinine = 2 x ULN -Absolute neutrophil count (ANC) = 1500/µL -Platelets = 100,000/µL -Hemoglobin = 9.0 g/dL -Administration of growth factors or blood transfusions will not be allowed within 4 weeks of the hematology labs required to confirm eligibility 12. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to randomization 13. Willingness and ability to comply with scheduled visits, treatment plans, laboratory and radiographic assessments, and other study procedures, including ability to swallow study drug tablets, the completion of patient reported outcomes questionnaires and long-term follow-up visits Eligibility Criteria for Placebo Subjects to Crossover to Open Label Apalutamide: 1a. Subject is willing and able to provide written informed consent to crossover to open-label apalutamide 2a. Subject has adequate organ function as defined by the following criteria: -Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruv
Exclusion criteria
Exclusion criteria: 1.Presence of distant metastases confirmed by blinded independent central review (BICR), including CNS and vertebral or meningeal involvement, or history of distant metastases. Exception: Pelvic lymph nodes < 2 cm in short axis (N1) located below the iliac bifurcation are allowed 2. Symptomatic loco-regional disease requiring medical intervention, such as moderate or severe urinary obstruction or hydronephrosis due to primary tumor (e.g., tumor obstruction of bladder trigone) 3. Prior treatment with second generation anti-androgens (e.g., enzalutamide) 4. Prior treatment with CYP17 inhibitors (e.g., abiraterone, orteronel, galerterone, ketoconazole, aminoglutethimide) 5. Prior treatment with radiopharmaceutical agents (e.g., Strontium-89), immunotherapy (e.g., sipuleucel-T), or any other investigational agent for NM-CRPC 6. Prior chemotherapy for prostate cancer except if administered in the adjuvant/neoadjuvant setting 7. History of seizure or condition that may pre-dispose to seizure (e.g., stroke within 1 year prior to randomization, brain arteriovenous malformation, Schwannoma, meningioma, or other benign CNS or meningeal disease which may require treatment with surgery or radiation therapy) 8. Concurrent therapy with any of the following (all must have been discontinued or substituted for at least 4 weeks prior to randomization): -Medications known to lower the seizure threshold (for a complete list please see Appendix 5) -Herbal (e.g. saw palmetto) and non-herbal (e.g. pomegranate)products that may decrease PSA levels (i.e., saw palmetto, pomegranate) -Systemic (oral/IV/IM) corticosteroids. Short term use (= 4 weeks) of corticosteroids during the study is allowed if clinically indicated, but it should be tapered off as soon as possible -Any other experimental treatment on another clinical trial - Agents indicated for the prevention of skeletal-related events in patients with solid tumors (e.g., denosumab [Xgeva®]) 9. History or evidence of any of the following conditions: -Any prior malignancy (other than adequately treated basal cell or squamous cell skin cancer, superficial bladder cancer, or any other cancer in situ currently in complete remission) within 5 years prior to randomization -Any of the following within 6 months prior to randomization: Severe/unstable angina, myocardial infarction, symptomatic congestive heart failure, arterial or venous thromboembolic events (e.g., pulmonary embolism, cerebrovascular accident including transient ischemic attacks), or clinically significant ventricular arrhythmias within 6 months prior to randomization - Uncontrolled hypertension systolic blood pressure =160 mmHg or diastolic BP =100 mmHg). Patients with a history of uncontrolled hypertension are allowed provided blood pressure is controlled by anti hypertensive treatment. -Gastrointestinal disorder affecting absorption -Active infection, such as human immunodeficiency virus (HIV) -Any other condition that, in the opinion of the Investigator, would impair the patient's ability to comply with study procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate superiority in the metastasis-free survival (MFS) of men with high risk NM-CRPC treated with Apalutamide versus placebo;Secondary Objective: - To compare the overall survival (OS) of men with high risk NM-CRPC treated with Apalutamide versus placebo and: - To compare the time to symptomatic progression in men with high risk NM-CRPC treated with Apalutamide versus placebo - To compare the time to initiation of cytotoxic chemotherapy in men with high risk NM-CRPC treated with Apalutamide versus placebo - To compare the progression-free survival (PFS) of men with high risk NM-CRPC treated with Apalutamide versus placebo - To compare the time to metastasis (TTM) in men with high risk NMCRPC treated with Apalutamide versus placebo - To evaluate the safety and tolerability of Apalutamide;Primary end point(s): Metastasis-Free Survival (MFS);Timepoint(s) of evaluation of this end point: MFS data for patients without metastasis or death will be censored on the date of the last tumor assessment (or, if no tumor assessment was performed after the baseline visit, at the date of randomization + 1 day). Tumor assessments will be performed at baseline and at 16-week intervals from randomization. Imaging studies will include a CT scan of the chest, abdomen, and pelvis, plus a bone scan. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For the secondary endpoints, a hierarchical testing will be performed in the following order: -Time to Metastasis (TTM) -Progression-Free Survival (PFS) -Time to symptomatic progression -Overall Survival (OS) -Time to initiation of cytotoxic chemotherapy;Timepoint(s) of evaluation of this end point: OS (every 4 months via clinic visit or telephone contact) | — |
Countries
Australia, Austria, Belgium, Canada, Czechia, Czech Republic, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Norway, Poland, Romania, Russian Federation, Slovakia, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Lead
Janssen Research & Development, LLC
Outcome results
None listed