Phase II Study to Assess the Efficacy of Niraparib Rechallenge After Surgery in Ovarian Cancer Patients With Oligometastatic Progression (The ANALLISA Study)
The ANALLISA study is a fast, proof-of-concept, phase II clinical trial which aims to assess the efficacy of niraparib rechallenge treatment after secondary cytoreductive surgery in ovarian cancer (OC) patients with oligometastatic progression (OMP) after first maintenance therapy with any PARP inhibitor. A total of 30 patients with OC and OMP will be enrolled and will receive treatment with niraparib 300 or 200 mg, according to body weight or platelet count. Patients will start treatment within 6 weeks after surgery and will receive it until progressive disease or treatment discontinuation. The main purpose of the study is to evaluate progression-free survival (PFS) of niraparib rechallenge in OC patients with OMP and no residual disease after secondary cytoreductive surgery.
• Written informed consent form (ICF) prior to beginning specific protocol procedures.
• Female patients ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Patients must have a life expectancy ≥16 weeks.
• Histologically confirmed high grade serous or endometrioid OC who have an OMP during or after the first maintenance therapy with any PARPi.
• Oligometastatic progression defined as 1-5 lesions (according to European Society for Radiotherapy and Oncology \[ESTRO\] and American Society for Radiation Oncology \[ASTRO\] consensus).
• Patients must have undergone secondary cytoreductive surgery with centrally confirmed no evidence of macroscopic residual tumor after surgery (complete resection).
• Patients must have either normal or up to 2 x ULN CA 125 level.
• Documented breast cancer gene 1/2 (BRCA1/2) status and homologous recombination (HR) status.
⁃ Patients who have received prior iPARP monotherapy or iPARP together with bevacizumab as maintenance treatment.
⁃ 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.
⁃ If prior treatment was niraparib, no significant toxicity or need for treatment discontinuation was required.
⁃ 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).
⁃ Able to take oral medications.
⁃ Patients must start treatment 3 to 6 weeks from surgery, once recovered from surgery.
⁃ 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.
⁃ 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.
⁃ Patients must be accessible for treatment follow-up.