Addition of Apalutamide to current standard therapy (hormonal therapy and radiation therapy) in patients with prostate cancer.
- Conditions
- Intermediate and Limited High Risk Localized Prostate CancerMedDRA version: 20.0Level: PTClassification code 10060862Term: Prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000899-15-BE
- Lead Sponsor
- European Organisation for Research and Treatment of Cancer (EORTC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 990
•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 - Favorable intermediate risk :
- Only one of the following intermediate risk factors: PSA 10-20 ng/mL, or Gleason score 7 (3+4) (international society of urological pathology-ISUP Grade 2), or cT2b
- Unfavorable intermediate risk :
- either PSA 10-20 ng/mL and cT2b,
- or Gleason score 7 (4+3) (ISUP Grade 3)
- Limited high risk: 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), <2.5 x upper limit of normal (ULN)
- total bilirubin <1.5 x upper limit of normal (ULN)
[NOTE: in subjects with Gilbert's syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin and if direct bilirubin is = 1.5 x ULN, subject may be eligible]
- creatinine level < 2 x ULN
- serum albumin = 3.0 g/dL
- serum potassium = 3.5 mmol/L
- hemoglobin = 10.0 g/dL (independent of transfusion and/or growth factors within 3 months prior to randomization)
- platelet count = 100 x 109/L (independent of transfusion and/or growth factors within 3 months prior to randomization)
•Age = 18 years and = 80 years
•Be able to swallow whole study drug tablets
•Patients with partners of childbearing / reproductive potential should agree to use a condom plus a highly effective method of birth control while on study drug and for at least 3 months following the last dose of study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly. Patients must also agree not to donate sperm during the study and for 3 months after receiving the last dose of study treatment.
•Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.
•Central pathology review on slides obtained at diagnosis for quality assurance purpose will be done.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 743
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 247
•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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method