NIRAPARIB TOSILATE MONOHYDRATE for Ovarian cancer (oligometastatic progression)

Inclusion criteria

• {"criterion_text":"- Written informed consent form (ICF) prior to beginning specific protocol procedures."}
• {"criterion_text":"- Patients must be accessible for treatment follow-up."}
• {"criterion_text":"- Female patients ≥ 18 years of age."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1."}
• {"criterion_text":"- Patients must have a life expectancy ≥16 weeks"}
• {"criterion_text":"- Histologically confirmed high grade serous or endometrioid OC who have an OMP during or after the first maintenance therapy with any PARPi"}
• {"criterion_text":"- Oligometastatic progression defined as 1-5 lesions (according to European Society for Radiotherapy and Oncology [ESTRO] and American Society for Radiation Oncology [ASTRO] consensus). Note: Metastatic lymph nodes located within the same anatomical lymph-node chain or station, as confirmed on surgical specimen, shall be counted collectively as one single metastatic lesion."}
• {"criterion_text":"- Patients must have undergone secondary cytoreductive surgery with centrally confirmed no evidence of macroscopic residual tumor after surgery (complete resection)."}
• {"criterion_text":"- Patients must have either normal or up to 2 x ULN CA 125 level."}
• {"criterion_text":"- Documented breast cancer gene 1/2 (BRCA1/2) status and homologous recombination (HR) status."}
• {"criterion_text":"- Patients with asymptomatic and treated brain metastases are allowed if: 1. Neurosurgical resection ≥ 28 days prior to initiation of study treatment. 2. Not requiring radiotherapy. 3. Not receiving steroid therapy or anticonvulsant for at least 7 days before the first dose of study treatment."}
• {"criterion_text":"- Patients who have received prior PARPi monotherapy or PARPi together with bevacizumab as maintenance treatment."}
• {"criterion_text":"- Patients should have had benefit of prior PARPi defined by exposure for ≥12 months (at least ≥ 18 months for patients who have a BRCA1/2 mutation) from initiation of PARPi maintenance until the date of OMP or have experienced a tumor progression after treatment completion. Tumor progression must have been confirmed by computed tomography (CT) and/or PET-CT scan"}
• {"criterion_text":"- If prior treatment was niraparib, no significant toxicity or need for treatment discontinuation was required."}
• {"criterion_text":"- Willingness to provide formalin fixed, paraffin embedded (FFPE) tumor tissue from primary, if available, and secondary surgeries and blood samples at screening, every 3 cycles (12 weeks), and at the end of treatment (EoT)."}
• {"criterion_text":"- Able to take oral medications."}
• {"criterion_text":"- Patients must start treatment 3 to 8 weeks from surgery, once recovered from surgery"}
• {"criterion_text":"- Women of childbearing potential who engage in heterosexual intercourse must agree to use institution specified method(s) of contraception and must refrain from donating eggs in the time period specified in the study protocol. Women of childbearing potential must have a negative serum or a highly sensitive urine pregnancy test within 72 hours before study treatment initiation."}
• {"criterion_text":"- Patient has adequate bone marrow, liver, and renal function: • Hematological: White blood cell (WBC) count > 3.0 x 109/L, absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100.0 x109/L, and hemoglobin ≥ 9.0 g/dL (≥ 5.6 mmol/L).• Hepatic: total bilirubin ≤ institutional upper limit of normal (ULN) (except for Gilbert’s syndrome); alkaline phosphatase (ALP) ≤ 2.5 times ULN; aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 1.5 times ULN. 11). • Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min/1.73 m2 for patients with creatinine levels above institutional normal."}

Exclusion criteria

• {"criterion_text":"- Patients with symptomatic or systemic progressive disease not fulfilling OMP disease criteria."}
• {"criterion_text":"- Patients with persistent toxicities (> Common Terminology Criteria for Adverse Events (CTCAE) grade 2) caused by previous cancer therapy."}
• {"criterion_text":"- Patients unable to swallow oral medication or with any lifethreatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of niraparib, or put the study outcomes at undue risk."}
• {"criterion_text":"- Patients with clinically significant cardiovascular disease such as uncontrolled hypertension, uncontrolled or symptomatic arrythmias, congestive heart failure (CHF), or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association (NYHA) Functional Classification."}
• {"criterion_text":"- Patients treated with previous PARPi therapy who have any known, persistent (>4 weeks), ≥Grade 3 anemia, neutrophil count decrease or platelet count decrease."}
• {"criterion_text":"- Patients with known history of human immunodeficiency virus (HIV), or active hepatitis C Virus (HCV), or active hepatitis B Virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics"}
• {"criterion_text":"- Patients with known hypersensitivity or allergy to prior niraparib treatment or any of the excipients of the product."}
• {"criterion_text":"- Patients who have received a transfusion of platelets or red blood cells, colony-stimulating factors or have any other laboratory abnormality within 2 weeks prior niraparib treatment that might confound or interfere with the study result."}
• {"criterion_text":"- Participation in another clinical trial, interventional or observational, until the Study's safety visit. Note: participation in retrospective studies or data analysis is allowed."}
• {"criterion_text":"- Patients who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study treatment."}
• {"criterion_text":"- Patients with myelodysplastic syndrome (MSD)/Acute myeloid leukemia (AML), with history of MSD/AML or with features suggestive of MDS/AML."}
• {"criterion_text":"- Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)."}
• {"criterion_text":"- Other malignancy unless curatively treated with no evidence of disease ≥ 5 years prior to study enrollment. Note: Patients with adequately non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) and stage 1 low grade endometrial carcinoma are not excluded."}
• {"criterion_text":"- Vaccination with any live virus vaccine within 28 days prior study treatment initiation."}
• {"criterion_text":"- Patients with residual disease after secondary cytoreductive surgery"}

Primary endpoints

• {"endpoint_text":"- PFS is defined as the period of time from niraparib treatment initiation until the subsequent disease progression or death, whichever occurs first, as determined locally by the investigator through the use of Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1).","definition_or_measurement_approach":"Determined locally by the investigator using RECIST v1.1; time from niraparib treatment initiation to disease progression or death."}

Secondary endpoints

• {"endpoint_text":"- PFS by biomarker status is defined as the period of time from niraparib treatment initiation until the subsequent disease progression or death, whichever occurs first, as determined locally by the investigator through the use of RECIST v.1.1, in patients’ subgroups.","definition_or_measurement_approach":"Determined locally by investigator using RECIST v1.1 within biomarker-defined subgroups (BRCAm, BRCAwt, HRD, HRP)."}
• {"endpoint_text":"- PFS by CA 125 is defined as the time from treatment initiation until disease progression or death, whichever occurs first, as determined locally by the investigator using Gynecologic Cancer Intergroup (GCIC) criteria for CA 125 biomarker.","definition_or_measurement_approach":"Determined locally by investigator using GCIC criteria for CA 125."}
• {"endpoint_text":"- PFS2 is defined as the time from treatment initiation to the earliest progression event after that used for the primary variable PFS, or date of death as determined locally by the investigator using RECIST v.1.1.","definition_or_measurement_approach":"Determined locally by investigator using RECIST v1.1; time from treatment start to next progression event or death."}
• {"endpoint_text":"- TFST is defined as the time from the date of treatment initiation to the earliest date of anti-cancer therapy start date following study treatment discontinuation, or death.","definition_or_measurement_approach":"Time from treatment initiation to start of first subsequent anti-cancer therapy after study discontinuation, or death."}
• {"endpoint_text":"- OS is defined as the period from treatment initiation to death from any cause, as determined locally by the investigator.","definition_or_measurement_approach":"Time from treatment initiation to death from any cause, determined locally."}
• {"endpoint_text":"- Number of AEs, SAEs and SUSARs according to the CTCAE v.5.0.","definition_or_measurement_approach":"Safety assessed by counting AEs, SAEs and SUSARs and grading per CTCAE v5.0."}

Spain

Earliest CTIS Part Ii Submission Date

18-03-2024

Latest Decision Or Authorization Date

28-11-2025

Processing Time Days

620

Number Of Sites

14

Number Of Participants

30

Primary sponsor

Full Name

Medica Scientia Innovation Research S.L.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

Almac Clinical Services Limited

Responsibilities

QP realease

Third parties

• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"QP realease","organisation_type":"Pharmaceutical company"}