very high risk localized or locally advanced 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
Trade Name: firmagon
Product Name: degarelix 120 mg
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: degarelix
CAS Number: 214766-78-6
Current Sponsor code: dega
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 on a systematic ultrasound guided biopsy of the prostate containing at least 8 cores. An MRI-fusion biopsy is allowed if taken because a previous biopsy was negative. A TURP specimen pathology is allowed. PSA = 10 ng/ml and two of the following 4 risk factors for relapse: ? PSA =20 ng/ml, ? Gleason sum =8, ? cN1 (regional LN with a short axis length >10mm by CT scan or MRI) or pathologically confirmed lymph nodes (pN1) (see Appendix H), ? cT3-T4 (by MRI or core biopsy) (ie. If PSA=20 ng/ml then only one of the other 3 risk factors is needed) ? M0 by standard imaging work-up (see chapter 6 for specification of standard work-up) ? Testosterone = 200 ng/dl ? Adequate renal function: calculated creatinine clearance = 50 mL/min (Appendix D) ? Magnesium and potassium within normal limits of the institution or corrected to within normal limits prior to the first dose of treatment. ? Patients with prolonged QT-intervals due to prescribed Class IA (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmic medication must be carefully evaluated for GnRH-agonist or GnRH antagonist use, because these drugs may prolong the QT-interval. ? Clinically normal cardiac function for-left ventricular ejection fraction (= 50%) as assessed either by multi-gated acquisition scan or cardiac ultrasound, triplicate 12 lead ECG without clinically relevant abnormalities. WHO Performance status 0-1 (see Appendix C) ? Age = 18 years and = 80 years ? Participants who have partners of childbearing potential must use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 3 months after 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 ? Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations. 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 295 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 590
Exclusion criteria
Exclusion criteria: ? Previous use of androgen deprivation therapy, antiandrogens. 5-alpha reductase inhibitors are allowed if interrupted for more than 6 months prior to entering the study ? History of severe untreated asthma, anaphylactic reactions or severe urticaria and/or angiodema. ? Hypersensitivity towards the investigational drug ? The following biological parameters :AST, ALT, total bilirubin, prothrombin time, serum albumin above upper level of normal range No severe hepatic impairment (Child Pugh C) ? History of gastro-intestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of the protocol treatment. ? History of pituitary or adrenal dysfunction ? Uncontrolled diabetes mellitus ? History of ulcerative colitis, Crohn's Disease, ataxia, telangiectasia, systemic lupus erythematosus, or Fanconi anemia. ? Clinically significant heart disease as evidence myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) class III or IV heart disease or cardiac ejection fraction measurement of 450 ms at baseline, or intake of medications that prolong the QT/QTc interval ? Uncontrolled hypertension (systolic BP = 160 mmHg or diastolic BP = 95 mmHg); patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment. ? Prior history of malignancies other than prostate adenocarcinoma (except patients with basal cell, squamous cell carcinoma of the skin), or the patient has been free of malignancy for a period of 3 years prior to first dose of study drug(s). Prior history of bladder cancer excludes the patient ? Prior radical prostatectomy (TURP or suprapubic adenomectomy for benign prostatic hyperplasia is allowed) ? Any contraindication to external beam radiotherapy ? Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule or any condition which, in the opinion of the investigator, would preclude participation in this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - to assess if GnRH antagonists improve progression free survival (progression that can be biological, clinical, or death) compared to GnRH agonists in combination with external beam radiation therapy in patients with high-risk localized or locally-advanced cancer ;Secondary Objective: - documentation of effect of GnRH antagonists on clinically significant cardiovascular events in the subgroup of patients at high risk of such events at baseline; - documentation of side effects and quality of life, I-PSS and urinary tract infections; - assessment of relative treatment effect on secondary efficacy endpoints (clinical progression, time to next line of systemic therapy, time on therapy, overall and cancer specific survival) and on PSA at 6 months after end of RT;Primary end point(s): progression-free survival;Timepoint(s) of evaluation of this end point: progression-free survival defined as the time in days from randomization to death, clinical or biochemical progression (Phoenix definition, whichever comes first (see chapter 7.2)) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Clinical progression-free survival 2. Time to next systemic anticancer therapy (including secondary hormonal manipulation) 3. Proportion of patients switching from GnRH antagonists to GnRH agonists and total effective duration of treatment with the originally allocated drug. 4. Overall survival 5. Prostate Cancer specific survival 6. PSA 7. The incidence of clinical cardiovascular events – CCE (i.e. arterial embolic or thrombotic events, hemorrhagic or ischemic cerebrovascular conditions, myocardial infarction, and other ischemic heart disease) in patients who had cardiovascular events before entering the trial and in those without such events. 8. The incidence of urinary tract infection 9. Patient reported outcomes - International Prostate Symptoms Score (I-PSS) (urinary symptoms) - Quality of Life (HRQoL) measured with EORTC QLQ-C30 and PR25 instruments with the overall health related quality of life scale as primary scale - EQ-5L (to enable a future health economics analysis) ;Timepoint(s) of evaluation of this end point: 1. at the time in days from randomization to the first event among: death, a clinical progression or the start of another line of systemic anti-neoplastic therapy 2. interval of time between randomization and the first day of initiation of a next line of systemic anti-neoplastic therapy 3. at switch time 4. from the date of randomization to the date of death 5. Prostate cancer-specific survival will be measured from the date of randomization to the date of death related to prostate cancer. 6. at six months after completion of RT 7. from the day of randomization to the first documentation of CCE or death 8. from the day of randomization to the first documentation of urinary tract infection 9. at baseline and duration follow-up for all patients in the study. | — |
Countries
Austria, Belgium, Denmark, France, Germany, Italy, Spain, Switzerland, United Kingdom
Contacts
Public ContactJulie Hermans
EORTC
Outcome results
None listed