Castration-Resistant Prostate Cancer MedDRA version: 16.0 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: ARN-509
CAS Number: 956104-40-8
Current Sponsor code: ARN-509
Other descriptive name: ARN-509
Concentration unit: % (W/W)
Sponsors
Aragon Pharmaceuticals
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 2. Castration-resistant prostate cancer demonstrated during continuous androgen deprivation therapy (ADT)/post orchiectomy, defined as 3 consecutive rises of PSA, 1 week apart, resulting in two 50% increases over the nadir, with the last PSA > 2 ng/mL 3. Maintain castrate levels of testosterone (=65 years) yes F.1.3.1 Number of subjects for this age range 840
Exclusion criteria
Exclusion criteria: 1. Presence of distant metastases, including CNS and vertebral or meningeal involvement. 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, galeterone, ketoconazole) 5. Prior treatment with radiopharmaceutical agents (e.g., Strontium-89), immunotherapy (e.g., sipuleucel-T), or any other investigational agent for NM-CRPC (e.g., denosumab [Xgeva®]) 6. Prior chemotherapy, 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 -Herbal and non-herbal products that may decrease PSA levels (i.e., saw palmetto, pomegranate juice) -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 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 -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 (= 160 mmHg systolic blood pressure and/or diastolic blood pressure = 100 mmHg) -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 ARN-509 versus placebo;Secondary Objective: To compare the overall survival (OS) of men with high risk NM-CRPC treated with ARN-509 versus placebo and: -To compare the time to symptomatic progression in men with high risk NM-CRPC treated with ARN-509 versus placebo -To compare the time to initiation of cytotoxic chemotherapy in men with high risk NM-CRPC treated with ARN-509 versus placebo -To compare the radiographic progression-free survival (PFS) of men with high risk NM-CRPC treated with ARN-509 versus placebo -To compare the time to metastasis (TTM) in men with high risk NM-CRPC treated with ARN-509 versus placebo -To compare patient reported outcomes (PROs) of health-related quality of life and prostate cancer-specific symptoms in men with high risk NM-CRPC treated with ARN-509 versus placebo -To evaluate the safety and tolerability of ARN-509 -To evaluate the population pharmacokinetics of ARN-509 -To evaluate the effect of ARN-509 on ventricular repolarization in a subset of patients from selected clinical sites;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): -Overall Survival (OS) -Time to symptomatic progression -Time to initiation of cytotoxic chemotherapy -Radiographic Progression-Free Survival (PFS) -Time to Metastasis (TTM);Timepoint(s) of evaluation of this end point: OS (every 4 months via clinic visit or telephone contact) | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, Denmark, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Norway, Poland, Russian Federation, Slovakia, Spain, Sweden, Taiwan, United Kingdom, United States
Contacts
Public ContactVP, Clinical Development
Aragon Pharmaceuticals
Outcome results
None listed