Non-Metastatic Castration-Resistant Prostate Cancer non-spread Castration-Resistant Prostate Cancer
Conditions
Interventions
apalutamide/matched placebo tablets will be administered orally on a continuous
daily dosing regimen, at a starting dose for apalutamide of
240 mg once daily (4 x 60-mg tablets). The only difference
Sponsors
Aragon Pharmaceuticals, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Criterion modified per amendment. 1.2 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 = 18 years 9. Eastern Cooperative Oncology Group (ECOG) Performance Status grade 0 or 1 10. Resolution of all acute toxic effects of prior therapy or surgical procedure to Grade 1 or baseline prior to randomization 11. Criterion modified per amendment 11.1 Criterion modified per amendment 11.2 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 pyruvic transaminase [SGPT]) = 1500/µL * Platelets >= 100,000/µL * Hemoglobin >= 9.0 g/dL o 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. Criterion modified per amendment 13.1 Willingness and ability to comply with scheduled visits, treatment plans, laboratory and radiographic assessmen
Exclusion criteria
Exclusion criteria: 1. Criterion modified per amendment 1.1 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. Criterion modified per amendment 4.1 Prior treatment with CYP17 inhibitors (e.g., abiraterone acetate, 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., prior 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. Criterion modified per amendment 8.1 Criterion modified per amendment 8.2 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 (i.e., saw palmetto) and non-herbal products (i.e., pomegranate) that may decrease PSA levels * Systemic (oral/IV/IM) corticosteroids. Short term use (=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 |
|---|---|
| Metastasis-Free Survival (MFS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints * Time to Metastasis (TTM) * PFS * Time to symptomatic progression * Overall survival (OS) * Time to initiation of cytotoxic chemotherapy Other Evaluations * Health-related quality of life and prostate cancer-specific symptoms * Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities * PSA Response * Time to PSA progression * Population PK * Assessment of ventricular repolarization * Second progression-free survival (PFS2) * Medical resource utilization (MRU) | — |
Countries
Netherlands
Outcome results
None listed