Trial Comparing Irradiation Plus Long Term Adjuvant Androgen Deprivation With GnRH Antagonist Versus GnRH Agonist Plus Flare Protection in Patients With Very High Risk Localized or Locally Advanced Prostate Cancer

NCT02799706 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: EORTC-1414
• Study Type: interventional
• Target: 885
• Locations: 8 countries
• Sites: 39

Brief Summary

The primary objective of the trial is to assess if GnRH antagonists in combination with external beam radiation therapy improve progression free survival (progression that can be biological, clinical, or death) compared to GnRH agonists in combination with external beam radiation therapy. Secondary objectives include:

• 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.

Conditions

Prostate Cancer

Keywords

Prostate cancer; GnRH antagonist; GnRH agonist; radiation therapy; very high risk localized prostate cancer; locally advanced prostate cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  The primary endpoint is progression-free survival defined as the time in days from randomization to death, clinical or biochemical progression, whichever comes first. Where * PSA progression based on Phoenix definition, i.e. a rise by 2 ng/mL or more above the nadir PSA (Ref. 17) confirmed by a second value measured minimum 3 months later * Clinical progression is defined as onset of obstructive symptoms requiring local treatment and demonstrated to be caused by cancer progression or evidence of metastases detected by clinical symptoms and confirmed by imaging * Start of another line of systemic therapy in absence of progression * Death due to any cause

  through study completion, an average of 1 year

Secondary Outcomes (6)

• Clinical progression-free survival

  through study completion, an average of 1 year

• Time to next systemic anticancer therapy (including secondary hormonal manipulation)

  through study completion, an average of 1 year

• ♦ Proportion of patients switching from GnRH antagonists to GnRH agonists

  through study completion, an average of 1 year

• ♦ Overall survival

  through study completion, an average of 1 year

• Incidence of clinical cardiovascular events

  through study completion, an average of 1 year

Study Arms (2)

GnRH agonist + radiation therapy (RT)

ACTIVE COMPARATOR

As the study investigates the effect of a drug given concomitantly to radiotherapy, all patients will be treated with the same treatment technique and target dose. The preferred treatment technique is intensity modulated radiotherapy (IMRT) + A GnRH-agonist will be given for the duration selected for each patient. A non-steroidal anti-androgen (e. g. flutamide, bicalutamide) will be given orally one week before the first injection of the GnRH agonist and will be continued for no longer than 8 weeks to protect against flare. Dose may vary due to availability of different brand names and pharmaceutical forms The start of antiandrogen must be registered as day 1 of treatment in the GnRH agonist arm.

Drug: approved GnRH agonist; Radiation: Radiotherapy

GnRH antagonist + radiation therapy (RT)

EXPERIMENTAL

As the study investigates the effect of two drugs given concomitantly to radiotherapy, all patients will be treated with the same treatment technique and target dose. The preferred treatment technique is intensity modulated radiotherapy (IMRT) +a GnRH antagonist will be given for a predefined duration of 18, 24, or 36 months as per institution policy. Each institution has to adhere to the chosen duration of treatment for all patients throughout the study

Drug: Degarelix; Radiation: Radiotherapy

Interventions

Degarelix DRUG

a GnRH antagonist will be given for a predefined duration of 18, 24, or 36 months as per institution policy

GnRH antagonist + radiation therapy (RT)

approved GnRH agonist DRUG

A non-steroidal anti-androgen (e. g. flutamide, bicalutamide) will be given orally one week before the first injection of the GnRH agonist and will be continued for no longer than 8 weeks to protect against flare.Dose may vary due to availability of different brand names and pharmaceutical forms The start of antiandrogen must be registered as day 1 of treatment in the GnRH agonist arm.

GnRH agonist + radiation therapy (RT)

Radiotherapy RADIATION

.As the study investigates the effect of two drugs given concomitantly to radiotherapy, all patients will be treated with the same treatment technique and target dose. The preferred treatment technique is intensity modulated radiotherapy (IMRT)

GnRH agonist + radiation therapy (RT); GnRH antagonist + radiation therapy (RT)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of prostate adenocarcinoma
• PSA ≥ 10 ng/ml and two of the following 4 criteria:
• 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),
• cT3-T4 (by MRI or core biopsy) (i.e. If PSA≥ 20 ng/ml then only one of the other 3 risk factors is needed)
• M0 by standard imaging work-up (see chapter 6.1.1.1)
• 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.
• WHO Performance status 0-1
• Age ≥ 18 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.

You may not qualify if:

• Previous use of androgen deprivation therapy (ADT), 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 angioedema.
• 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 disorder 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 erythematous, 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 \< 50 % at baseline
• Coronary revascularization (PCI or multivessel CABG), carotid artery or iliofemoral artery revascularization (percutaneous or surgical procedure) within the last 30 days prior to entering the trial
• 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, 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)
• Prior brachytherapy or other radiotherapy that would result in an overlap of radiotherapy fields

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (39)

Hopitaux Universitaires Bordet-Erasme - Hopitaux Universitaires Bordet- Institut Jules Bordet

Brussels, 1000, Belgium

Location

Hopitaux Universitaires Bordet-Erasme - Hopital Universitaire Erasme

Brussels, 1070, Belgium

Location

Universitair Ziekenhuis Brussel

Brussels, 1090, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

Hopital De Jolimont

Haine-Saint-Paul, 7100, Belgium

Location

AZ Groeninge Kortrijk - Campus Kennedylaan

Kortrijk, 8500, Belgium

Location

CHU Ucl Namur - Site Sainte-Elisabeth

Namur, 5000, Belgium

Location

Gasthuiszusters van Antwerpen - GasthuisZusters Antwerpen - Sint-Augustinus

Wilrijk, 2610, Belgium

Location

University Hospitals Copenhagen - Rigshospitalet

Copenhagen, 2100, Denmark

Location

Clinique de l'Europe

Amiens, 80090, France

Location

Centre de radiotherapie Marie Curie

Arras, 6200, France

Location

Centre D'Onco. & Radioth. De Haute Energie Du Pays Basque

Bayonne, 64100, France

Location

Groupe Radiopole Artois - Centre de Radiotherapie Pierre Curie

Beuvry, 62660, France

Location

CHU de Grenoble - La Tronche - Hôpital A. Michallon

Grenoble, 38043, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Institut de Cancerologie de l'Ouest (ICO) - Centre Rene Gauducheau

Nantes, 44805, France

Location

Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere

Paris, 75651, France

Location

Centre Hospitalier Privé Saint-Grégoire

Saint-Grégoire, 35760, France

Location

Clinique Pasteur-Toulouse-Atrium

Toulouse, BP27617, France

Location

Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

Berlin, 12200, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Otto-Von-Guericke-Universitaet Magdeburg - Universitaetsklinik

Magdeburg, 39120, Germany

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

Location

AUSL Romagna - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, 47014, Italy

Location

Fundacion Hospital Alcorcon

Alcorcón, 28922, Spain

Location

Institut Catala d'Oncologia - ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)

Barcelona, 08916, Spain

Location

Clinica IMQ Zorrotzaurre

Bilbao, 48014, Spain

Location

Hospital General Universitario Santa Lucia

Cartagena, 30202, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, 14004, Spain

Location

Hospital Universitario de Gran Canaria Doctor Negrin

Las Palmas de Gran Canaria, 35010, Spain

Location

Complejo Hospitalario A

Pamplona, Spain

Location

Corporacio Sanitaria Parc Tauli

Sabadell, 08208, Spain

Location

Hospital Universitario de Salamanca

Salamanca, 37007, Spain

Location

Hospital Consorci Sanitari De Terrassa

Terrassa, 08227, Spain

Location

Complejo Hospitalario Universitario de Vigo -CHUVI - Hospital Alvaro Cunqueiro

Vigo, 36312, Spain

Location

Oncology Institute of Southern Switzerland (IOSI) - Oncology Institute of Southern Switzerland - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Inselspital

Bern, 3010, Switzerland

Location

Hôpitaux universitaires de Genève - HUG - site de Cluse-Roseraie

Geneva, Switzerland

Location

Nottingham University Hospitals NHS Trust - City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

• Zengerling F, Jakob JJ, Schmidt S, Meerpohl JJ, Blumle A, Schmucker C, Mayer B, Kunath F. Degarelix for treating advanced hormone-sensitive prostate cancer. Cochrane Database Syst Rev. 2021 Aug 5;8(8):CD012548. doi: 10.1002/14651858.CD012548.pub2.

  PMID: 34350976 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; Radiotherapy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Dirk Boehmer, MD, PhD

  Charite - Universitaetsmedizin Berlin - Campus Benjamin Franklin

  PRINCIPAL INVESTIGATOR

• Pedro Lara, MD, PhD

  San Roque University Hospital

  PRINCIPAL INVESTIGATOR

• Thomas Zilli, MD, PhD

  Hôpitaux universitaires de Genève - HUG - site de Cluse-Roseraie

  PRINCIPAL INVESTIGATOR

• Martin Spahn, MD, PhD

  Group Of Private Clinics Hirslanden - Hirslanden Klinik Zurich

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2016
• First Posted: June 15, 2016
• Study Start: September 25, 2017
• Primary Completion: August 23, 2023
• Study Completion (Estimated): June 30, 2026
• Last Updated: May 22, 2026

Record last verified: 2026-05

Locations

DK (1); CH (3); BE (8); DE (3); IT (2); GB (1); ES (11); FR (10)