Darolutamide for Prostate cancer (hormone‑naïve)

Inclusion criteria

• {"criterion_text":"- Aged 18 years or older\n- Able to swallow the study drug whole as a tablet\n- Adequate bone marrow function • absolute neutrophil count (ANC) ≥ 1.5 109/L. • hemoglobin ≥ 10.0 g/dl. • platelets ≥ 100 109/L.\n- Adequate renal function: creatinine ≤ 1.5 x ULN\n- Albumin > 25 g/L\n- Adequate hepatic function: • Bilirubin: total bilirubin ≤ 1.5 × upper limit of normal (ULN). • AST and/or ALT ≤ 2.5 × ULN.\n- Normal 12-lead ECG as per local standard\n- Patients of reproductive potential should use adequate birth control measures, during the study treatment period and for at least 3 months after the last 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- Absence 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\n- Before patient registration/randomization, written informed consent must be given according to ICH/GCP, and national/local regulations.\n- Histologically confirmed prostate cancer (all stages) for whom continuous ADT is indicated for a minimum period of 24 weeks\n- M0 patients or those presenting with a maximum of 4 confirmed metastatic lesions, including bone, extra-pelvic lymph nodes, and > 2 cm pelvic lymph nodes by imaging (contrast enhanced CT scans or MRI, Tc-99m BS according to local practice, see section 6.1.1). Visceral metastases are excluded\n- Asymptomatic for metastatic prostate cancer; urinary symptoms are allowed\n- Baseline total testosterone ≥ 8 nmol/L or 230 ng/dL\n- Two subsequent PSA values ≥ 2 ng/ml, done in the past 3 months (prior to enrollment) with a minimum of 2 weeks between the two, with the second being equal to or higher than the first\n- WHO performance status (PS) of 0-1\n- G8 score ≥ 14 for patients aged ≥ 70 years old\n- A life expectancy of at least 12 months"}

Exclusion criteria

• {"criterion_text":"- Previously or currently receiving hormonal therapy with intent to treat prostate cancer disease (surgical castration or other hormonal manipulation, e.g. LHRH agonists, LHRH antagonists, anti-androgens, oestrogens, 5α-reductase inhibitor). For patients that have received (neo)adjuvant ADT before radiotherapy, it should have been stopped for more than 1 year\n- History of prior malignancy. Adequately treated basal cell or squamous cell carcinoma of skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e. pTis, pTa, and pT1) is allowed, as well as any other cancer from which the patient has been disease-free for a period of at least 5 years.\n- Clinically significant cardiovascular disease including: • Myocardial infarction within 6 months prior to randomization • Uncontrolled angina within 3 months prior to randomization • Coronary/peripheral artery bypass within 6 months prior to randomization • Stroke within 6 months prior to randomization • Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition scan (MUGA) performed within 3 months results in a left ventricular ejection fraction that is ≥ 45% • History of clinically significant ventricular arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, torsades de pointes) • History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\n- Uncontrolled hypertension as indicated by a resting systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg at the screening visit\n- Prior use of investigational agents that block androgen synthesis or block androgen receptor\n- Use of herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (e.g. saw palmetto)\n- Has received systemic glucocorticoids within 24 weeks prior to enrollment or is expected to require systemic glucocorticoids during the study period, unless determined to be medically necessary by the investigator for other indications than prostate cancer\n- Radiation therapy for treatment of the primary tumor within 3 months prior to enrollment\n- Use of an investigational agent within 4 weeks prior to enrollment is not allowed\n- Gastrointestinal disorder affecting absorption (e.g. gastrectomy, active peptic ulcer disease) within 3 months prior to enrollment\n- Known hypersensitivity to the study treatment or any of its ingredients (refer to Investigator's brochure).\n- Severe or uncontrolled concurrent disease, infection or co-morbidity including active viral hepatitis, known human immunodeficiency virus infection with detectable viral load (HIV) or chronic liver disease (Child Pugh C)"}

Primary endpoints

• {"endpoint_text":"- The primary endpoint is the PSA response assessed at 24 weeks. PSA response is defined as a ≥ 80% decline in PSA measurement taken at week 24 relative to the measurement taken at baseline, in the darolutamide study arm. The ADT arm is used as an internal control.","definition_or_measurement_approach":"PSA response defined as a ≥ 80% decline in PSA at week 24 relative to baseline in the darolutamide arm; ADT arm used as internal control."}

Secondary endpoints

• {"endpoint_text":"- The main key secondary endpoint in this study is the change in hormone-treatment related symptoms scale of the EORTC QLQ-PR25 at 24 weeks compared to baseline in the darolutamide study arm. A 10-point difference is regarded as a clinically meaningful benefit.","definition_or_measurement_approach":"Change from baseline to 24 weeks on the hormone-treatment related symptoms (HTR) scale of the EORTC QLQ-PR25; ≥10-point difference regarded as clinically meaningful."}
• {"endpoint_text":"- Safety according to NCI-CTC version 4.0","definition_or_measurement_approach":"Adverse events graded using NCI Common Terminology Criteria for Adverse Events (CTC) version 4.0."}
• {"endpoint_text":"- Objective response rate at 24 weeks in patients with RECIST 1.1 measurable disease at baseline","definition_or_measurement_approach":"Objective response assessed per RECIST 1.1 at 24 weeks in patients with measurable disease at baseline."}
• {"endpoint_text":"- PSA complete response rate at 24 weeks defined as a ≥ 90% decline in PSA measurement at week 24 relative to the measurement taken at baseline","definition_or_measurement_approach":"PSA complete response defined as ≥ 90% decline in PSA at week 24 relative to baseline."}

Italy

Earliest CTIS Part Ii Submission Date

29-05-2024

Latest Decision Or Authorization Date

29-05-2024

Processing Time Days

0

Number Of Sites

1

Number Of Participants

90

Spain

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

23-05-2025

Processing Time Days

365

Number Of Sites

5

Number Of Participants

32

France

Earliest CTIS Part Ii Submission Date

23-05-2024

Latest Decision Or Authorization Date

26-05-2025

Processing Time Days

368

Number Of Sites

2

Number Of Participants

13

Belgium

Earliest CTIS Part Ii Submission Date

27-05-2024

Latest Decision Or Authorization Date

23-05-2025

Processing Time Days

361

Number Of Sites

4

Number Of Participants

34

Primary sponsor

Full Name

European Organisation For Research And Treatment Of Cancer

Organisation Type

Patient organisation/association

Country Of Registered Address

Belgium

Third parties

• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"Drug supply and labelling","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Cliniques Universitaires Saint-Luc","duties_or_roles":"Blood samples biobanking and translational research; additional sponsor duties coded in record","organisation_type":"Hospital/Clinic/Other health care facility"}