Intermediate and Limited High Risk Localized 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
Interventions
Product Name: Apalutamide
Product Code: JNJ-56021927
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: APALUTAMIDE
CAS Number: 956104-40-8
Current Sponsor code: JNJ-56021927
Other descripti
Sponsors
European Organisation for Research and Treatment of Cancer (EORTC)
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: •Histologically confirmed diagnosis of prostate adenocarcinoma diagnosed by ultrasound guided biopsy of the prostate containing 10-12 cores showing no neuroendocrine component at local institution. (An MRI-fusion biopsy is allowed if taken because a previous biopsy was negative.) •PSA 20 ng/mL or Gleason score >7 (ISUP Grade 4/5) •M0 by standard imaging work-up •Scheduled to be treated with primary prostate RT •ECOG/WHO Performance Status = 2 •The following laboratory values done within 4 weeks before randomization: - aspartate aminotransferase (AST), alanine aminotransferase (ALT), 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is = 1.5 x ULN, subject may be eligible] - creatinine level =65 years) yes F.1.3.1 Number of subjects for this age range 247
Exclusion criteria
Exclusion criteria: •cT2c, T3, T4 or pelvic lymph nodes involvement, as assessed by CT scan or MRI (cN1) or pelvic lymph node dissection (pN1) •Previous pelvic irradiation or radical prostatectomy. •Bilateral orchiectomy •Prior systemic (e.g., chemotherapy) or procedural (e.g., prostatectomy, cryotherapy) treatment for prostate cancer •Prior treatment with 5-alpha reductase inhibitors for benign prostatic hypertrophy not discontinued 4 weeks prior to randomization •Prior treatment with any LHRH agonist or antagonist, bicalutamide, flutamide or nilutamide, enzalutamide, abiraterone acetate, orteronel, galeterone, ketoconazole, aminoglutethimide, estrogens, megestrol acetate, and progestational agents for prostate cancer •Prior treatment with radiopharmaceutical agents (e.g., strontium-89) or immunotherapy for prostate cancer •Other malignancy except adequately treated basal cell carcinoma of the skin or other malignancy from which the patient has no evidence of disease for at least 5 years. •History of Ulcerative Colitis, Crohn's Disease, Ataxia Telangiectasia, systemic lupus erythematosus or Fanconi anemia •History of seizure or condition that may predispose to seizure (including but not limited to: a) prior stroke, transient ischemic attack or loss of consciousness, any of which occurred = 1 year prior to randomization; b) brain arteriovenous malformation; or c) intracranial masses such as schwannomas and meningiomas that are causing edema or mass effect). •Medications known to lower the seizure threshold (see list under prohibited medication, section 5.4.4) must be discontinued or substituted at least 4 weeks prior to study entry •Certain risk factors for abnormal heart rhythms/QT prolongation: torsade de pointes ventricular arrhythmias (e.g., heart failure, hypokalemia, or a family history of a long QT syndrome), a QT or corrected QT (QTc) interval > 450 ms at baseline •Uncontrolled hypertension (systolic BP = 140 mmHg or diastolic BP = 90 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment •Bilateral hip prostheses •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 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 •Known or suspected contraindications or hypersensitivity to apalutamide, bicalutamide or LHRH agonists or any of the components of the formulations •Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: •to characterize the safety profile of the combination treatment by radiation with LHRH agonists and apalutamide in patients •To characterize the early effect of addition of apalutamide to treatment with androgen deprivation therapy (ADT) and radiation (RT) on the PSA values on treatment assessed by the value measured at 6 months and by the lowest value achieved on treatment (PSA nadir) •To determine if the combination of apalutamide with 6 months of ADT and RT improves - the biochemical progression-free survival with biochemical relapse defined according to the Phoenix criteria of these patients - the metastasis-free survival of these patients - the overall survival and prostate-cancer specific survival of these patients •To assess the impact of the addition of apalutamide to the combined RT and ADT on the health related quality of life of the patients measured by mean hormone-treatment related symptoms scale of the QLQ PR25, and by the IPSS score.;Primary end point(s): The primary trial endpoint is disease-free survival . Disease-free survival (DFS) is defined as the interval from the date of randomization to the date of first evidence of loco-regional recurrences, distant metastases, initiation of other anticancer treatment for prostate cancer or death from any cause, whichever occurs first, or the date of last known follow-up alive without any of these events.;Timepoint(s) of evaluation of this end point: The primary trial analysis ("final analysis") is planned to take place when 87 events of DFS have been observed.;Main Objective: To determine if the combination of apalutamide with 6 months of androgen deprivation therapy by LHRH agonists in patients with intermediate and limited high-risk, localized prostate cancer receiving primary radiation therapy results in an improvement of disease-free survival evaluated by the treating physician, in comparison to the combination of radiation and androgen deprivation therapy without the addition of a | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Progression-free survival that includes first events of biochemical failure by Phoenix criteria in addition to the events listed in the primary endpoint DFS. •Metastasis-free survival •Overall survival •Prostate cancer specific survival •PSA value at the end of the 6 months of treatment •PSA nadir observed on treatment •Health-related quality of life evaluated using self-administered EORTC QLQ-C30 questionnaire and EORTC QLQ-PR25 instruments. •Adverse events graded according to the National Cancer Institute Common Terminology Criteria for adverse events (NCI-CTCAE) version 5.0;Timepoint(s) of evaluation of this end point: at the final analysis | — |
Countries
Belgium, Denmark, France, Germany, Italy, Poland, Spain, Switzerland
Contacts
Public ContactRegulatory Affairs Department
European Organisation for Research and Treatment of Cancer (EORTC)
Outcome results
None listed