DEGARELIX for Prostate cancer | Locally advanced prostate cancer

Inclusion criteria

• {"criterion_text":"- Patients may enter the trial in the clinical setting where a combination therapy involving irradiation combined with androgen deprivation therapy is envisaged.\n- For all patients: Adequate bone marrow function (absolute neutrophil count (ANC) ≥ 1.5 109/L; hemoglobin ≥ 10.0 g/dl; platelets ≥ 100 109/L)\n- For all patients: Adequate hepatic function: (1) Bilirubin: total bilirubin ≤ 1.5 x upper limit of normal (ULN). (2) AST and/or ALT ≤ 2.5 x ULN.\n- For all patients: Adequate renal function: calculated creatinine clearance ≥ 50 mL/min\n- For all patients: Magnesium and potassium within normal limits at the institution\n- For all patients: WHO Performance status 0-1\n- For all patients: Age ≥ 18 and ≤ 80 years\n- For all patients: 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\n- For all patients: Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.\n- For patients planned for primary radiotherapy: 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. 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); cT3-T4 (by MRI or core biopsy).\n- For all patients: Either of (1) M0 according to standard imaging methods (i.e. bone scan and conventional CT/MR image) or M0 according to modern imaging methods (i.e. whole-body MRI, PET/CT); (2) M0 according to bone scan and conventional CT/MR image and M1a and M1b only with ≤ 3 lesions detected by modern imaging methods are also allowed, called \"Oligometastatic disease\". Patients with oligometastatic disease will undergo metastasis targeted therapy.\n- For all patients: Testosterone ≥ 200 ng/dL"}

Exclusion criteria

• {"criterion_text":"- M1c, confirmed by any imaging method or biopsy\n- Any contraindication to external beam radiotherapy\n- 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.\n- Previous use of androgen deprivation therapy, antiandrogens if not interrupted for more than 6 months prior to entering the study\n- History of severe untreated asthma, anaphylactic reactions or severe urticaria and/or angiodema.\n- Hypersensitivity towards any of the active substances, the excipients used and synthetic GnRH or GnRH derivatives\n- No severe hepatic impairment (Child Pugh C)\n- Uncontrolled diabetes mellitus\n- Coronary revascularization (PCI or multivessel CABG), carotid artery or iliofemoral artery revascularizaton (percutaneous or surgical procedure) within the last 30 days prior to entering the trial\n- Certain risk factors for abnormal heart rhythms/QT prolongation: torsade de pointes ventricular arrhythmias (eg, heart failure, hypokalemia, or a family history of a long QT syndrome), a QT or corrected QT (QTc) interval >450 ms\n- 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 (except appropriately treated Tis or T1a) excludes the patient"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is the proportion of patients with PSA nadir < 0.1 ng/mL within 6 months following completion of RT.","definition_or_measurement_approach":"Proportion of patients achieving PSA nadir < 0.1 ng/mL measured within 6 months after completion of radiotherapy (PSA measurements collected post-RT and threshold applied)."}

Secondary endpoints

• {"endpoint_text":"- 1. Clinical progression-free survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- 2. Time to next systemic anticancer therapy","definition_or_measurement_approach":""}
• {"endpoint_text":"- 3. Time to next systemic anticancer therapy other than ADT","definition_or_measurement_approach":""}
• {"endpoint_text":"- 4. Proportion of patients switching from GnRH antagonists to GnRH agonists and total effective duration of treatment with the originally allocated drug.","definition_or_measurement_approach":""}
• {"endpoint_text":"- 5. Overall survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- 6. Prostate Cancer specific survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- 7. PSA","definition_or_measurement_approach":"PSA measured at 6 months after end of radiotherapy for comparison between arms."}
• {"endpoint_text":"- 8. 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.","definition_or_measurement_approach":"Incidence rates of predefined clinical cardiovascular events collected and compared between subgroups (patients with prior CV events at baseline vs those without)."}
• {"endpoint_text":"- 9. The incidence of urinary tract infection","definition_or_measurement_approach":""}
• {"endpoint_text":"- 10. Patient reported outcomes: (a) International Prostate Symptoms Score (I-PSS) (urinary symptoms); (b) Quality of Life (HRQoL) measured with EORTC QLQ-C30 and PR25 instruments with the overall health related quality of life scale as primary scale; (c) EQ-5L (to enable a future health economics analysis)","definition_or_measurement_approach":"PRO instruments: I-PSS, EORTC QLQ-C30 and PR25, and EQ-5D-5L collected per schedule; overall HRQoL scale of QLQ-C30 is primary PRO scale."}
• {"endpoint_text":"- 11. Progression free survival defined as the time in days from randomization to death, clinical or biochemical progression or to the start of another line of systemic anti-neoplastic therapy in absence of progression or further systemic antineoplastic therapy, whichever comes first","definition_or_measurement_approach":"Progression-free survival measured in days from randomization to death, clinical or biochemical progression, or start of another systemic anti-neoplastic therapy (whichever occurs first)."}

Belgium

Latest Decision Or Authorization Date

12-08-2024

Number Of Sites

1

Number Of Participants

115

Germany

Latest Decision Or Authorization Date

14-08-2024

Number Of Sites

1

Number Of Participants

87

Spain

Latest Decision Or Authorization Date

07-08-2024

Number Of Sites

4

Number Of Participants

274

Primary sponsor

Full Name

Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi

Organisation Type

Patient organisation/association

Country Of Registered Address

Belgium

Third parties

• {"country":"Belgium","full_name":"Cliniques Universitaires Saint-Luc","duties_or_roles":"Biobank","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"Other - For all countries: Biological sample shipment","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Klinikos Limited","duties_or_roles":"Monitoring in Germany","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"Spain only: Degarelix labeling, QP release and distribution to sites","organisation_type":"Pharmaceutical company"}