NIRAPARIB, ABIRATERONE ACETATE for Prostate cancer | Metastatic hormone-sensitive prostate cancer | Metastatic castration-resistant prostate cancer

Inclusion criteria

• {"criterion_text":"- Male patients, aged above 18 years, with histologically confirmed prostate adenocarcinoma, initiating systemic therapy for metastatic disease, encompassing: ○\tNewly diagnosed (i.e. de-novo) metastatic hormone-sensitive prostate cancer (mHSPC) or ○\tRecurrent (i.e. metachronous) mHSPC ■\tPatients that have had prior local treatment with curative intent (e.g. primary radiotherapy or radical prostatectomy) and subsequently develop metachronous metastatic disease. These metachronous or recurring mHSPC patients are those observed in the setting of rising PSA until metastasis develops. Patients are not required to be ADT-naïve, but must have normal levels of testosterone (>50 ng/dL or 1.7 nmol/L) at ProBio screening and liquid biopsy collection or ○\tFirst-line mCRPC, i.e. first evidence of progressive metastatic prostate cancer under castrate levels (<50 ng/dL) of serum testosterone, as defined by the EAU guidelines, encompassing: ■\tBiochemical progression: Three consecutive rises in PSA 1 wk apart, resulting in two 50% increases over the nadir, and PSA >2 ng/ml and/or ■\tRadiologic progression: The appearance of new lesions: either two or more new bone lesions on bone scan or a soft tissue lesion using the Response Evaluation Criteria in Solid Tumours."}
• {"criterion_text":"- For the initial identification of patients with metastatic disease, distant metastases can either be identified by conventional imaging (i.e. bone scan or metastatic lesions on CT or MRI), or molecular imaging (i.e. miM1 disease on prostate-specific membrane antigen (PSMA) targeting positron emission tomography (PET)). Radiology taken within 6 weeks of screening may be used, if older a new scan needs to be taken. It is important to note that PSMA PET/CT can be used for initial identification and enrollment of patients with metastatic disease, but that it may not be used for response assessment or to infer disease progression. Radiographic follow-up and assessment of progression need to be performed with conventional imaging."}
• {"criterion_text":"- Adequate health, hematologic, hepatic, and renal function, as assessed by the investigator, to receive all available treatments in the trial in each disease state (mHSPC and mCRPC) (i.e. haemoglobin ≥ 100 g/L (blood transfusion not less than 21 days prior to screening), absolute neutrophil count ≥ 1.5 x 10^9/L, platelets ≥100 x 10^9/L and Total bilirubin < 1.5 ULN (patients with Gilberts Syndrome bilirubin < 40 µg/L) and AST and ALT ≤ 1.5 ULN (or ≤ 3 ULN in the presence of liver metastases) and serum creatinine not greater than 1 ULN (if serum creatinine is between 1 and 1.5 ULN, patients may be eligible provided that the calculated GFR is at least 50 ml/min measured directly by 24-hour urine sampling OR using Cockcroft-Gault method)"}
• {"criterion_text":"- Albumin greater than or equal to 28 g/L"}
• {"criterion_text":"- ECOG/WHO performance status 0-2"}
• {"criterion_text":"- Agrees to use an effective contraceptive method during and up to 6 months after study drug treatment and should not donate sperm during this period."}
• {"criterion_text":"- Able to understand the patient information and sign written informed consent."}

Exclusion criteria

• {"criterion_text":"- Other malignancies within 5 years except non-melanoma skin cancer"}
• {"criterion_text":"- Within 6 months of randomisation: myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke, TIA, or congestive heart failure NYHA class III or IV"}
• {"criterion_text":"- Uncontrolled hypertension: SBP > 160 mmHg and or DBP > 95 mmHg. Subjects with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive treatment"}
• {"criterion_text":"- Uncontrolled hypotension: SBP < 90 mmHg and/or DBP < 50 mmHg"}
• {"criterion_text":"- Upon entering the mHSPC phase of the trial, prior systemic therapy (including ADT) is not allowed. Patients with mCRPC may not enter the trial when they have already received prior systemic therapy (with the exception of standard ADT) for mCRPC."}
• {"criterion_text":"- Any severe acute or chronic medical condition that places the patient at increased risk of serious toxicity or interferes with the interpretation of study results. This includes a medical history significant for arrhythmia (e.g. multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted to enter the study based on the Investigators judgement with cardiologist consultation recommended."}
• {"criterion_text":"- Unable to comply with study procedures"}
• {"criterion_text":"- Current participation in another clinical trial that will be in conflict with the present study, e.g. administration of an investigational therapeutic or invasive surgical procedure within 28 days prior to study enrolment. Imaging-based interventional trials are allowed as long as the conventional imaging intervals within ProBio are preserved."}
• {"criterion_text":"- Patients who are unlikely to comply with the protocol (e.g. uncooperative attitude, inability to return for subsequent visits) and/or otherwise considered by the Investigator to be unlikely to complete the study"}
• {"criterion_text":"- Any condition or situation which, in the opinion of the investigator, would put the subject at risk, may confound study results, or interfere with the subject’s participation in this study. This includes a history of QT prolongation associated with other medications that required discontinuation of that medication; and other factors that increase the risk of OTc prolongation or risk of arrhythmic events, hypokalemia of grade >1, potential for Torsade de Pointes, congenital long QT syndrome."}
• {"criterion_text":"- Any medical condition that would make use of the study treatments contraindicated, according to the SmPC, e.g. significant heart or liver disease. The investigator should check the SmPC and/or IB for the assigned study treatments. This includes a family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives."}
• {"criterion_text":"- The determination of a biomarker signature is necessary to randomise patients during ProBio mCRPC. Patients with detectable ctDNA and having a microsatellite unstable (MSI) or hypermutated tumor will be excluded from the trial since the plethora of mutations obscures a proper assessment of the disease-driving biomarker signature. Patients will therefore be excluded in case of: a.\tFor patients in mCRPC: undetectable levels of ctDNA. b.\tFor patients in mHSPC and mCRPC: microsatellite unstable (MSI+) or hypermutated tumor."}

Primary endpoints

• {"endpoint_text":"- Progression-free survival, where progression is defined according to disease stage at trial entry: ●\tFor mHSPC: Time to development of castration-resistance (European Association of Urology [EAU] guidelines) or death ●\tFor mCRPC: Time to no longer clinical benefiting (NLCB) (Prostate Cancer Working Group [PCWG3] guidelines)","definition_or_measurement_approach":"Progression defined by disease stage at entry: for mHSPC measured as time to development of castration-resistance (EAU guidelines) or death; for mCRPC measured as time to no longer clinical benefiting (NLCB) per PCWG3 guidelines."}

Secondary endpoints

• {"endpoint_text":"- 1.Overall survival (OS).","definition_or_measurement_approach":"Overall survival measured as time from randomisation to death from any cause."}
• {"endpoint_text":"- 2. Quality of life assessed by In all patients enrolled in ProBio: ●\tEORTC-QLQ-C30 ●\tEQ-5D-5L ●\tBPI-SF In patients enrolled in ProBio with ctDNA-undetectable mHSPC: EORTC QLQ-PR25 (hormonal and sexual subdomains).","definition_or_measurement_approach":"Quality of life measured using EORTC-QLQ-C30, EQ-5D-5L, BPI-SF for all patients; for ctDNA-undetectable mHSPC patients also EORTC QLQ-PR25 (hormonal and sexual subdomains)."}
• {"endpoint_text":"- 3. Cost effectiveness will be assessed by using the EQ-5D-5L instrument to estimate health utilities. Treatment costs will be based on drug costs and reimbursement data.","definition_or_measurement_approach":"Cost-effectiveness assessed using EQ-5D-5L to derive health utilities; treatment costs based on drug costs and reimbursement data."}
• {"endpoint_text":"- 4. Frequency and severity of adverse events (AE).","definition_or_measurement_approach":"Safety assessed by frequency and severity of adverse events (AE) (standard CTCAE reporting)."}

Norway

Earliest CTIS Part Ii Submission Date

30-05-2024

Latest Decision Or Authorization Date

13-04-2026

Processing Time Days

683

Number Of Sites

6

Number Of Participants

250

Belgium

Earliest CTIS Part Ii Submission Date

30-05-2024

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

680

Number Of Sites

11

Number Of Participants

750

Sweden

Earliest CTIS Part Ii Submission Date

30-05-2024

Latest Decision Or Authorization Date

10-04-2026

Processing Time Days

680

Number Of Sites

12

Number Of Participants

750

Primary sponsor

Full Name

Karolinska Institutet

Organisation Type

Educational Institution

Country Of Registered Address

Sweden

Third parties

• {"country":"Sweden","full_name":"Prostatacancerförbundet, Sweden.","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"Switzerland","full_name":"Bayer Consumer Care AG, Switzerland.","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"Sweden","full_name":"Janssen Pharmaceutical NV, Sweden.","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"Belgium","full_name":"Kom op tegen Kanker, Belgium.","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"Sweden","full_name":"Vetenskapsrådet, Sweden.","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"Sweden","full_name":"Astra Zeneca, Sweden.","duties_or_roles":"Source of monetary support","organisation_type":""}