Niraparib Monotherapy as Maintain and Recurrent Treatment of Endometrial Serous Carcinoma: A Multi-center, Open-label, Prospective Clinical Study
Endometrial Serous carcinoma (ESC) has similar molecular characteristics to high-grade serous ovarian carcinoma (HGSOC) and basal cell-like breast cancer, such as similar Chromosomal instability, somatic copy number variation profiles and somatic mutations. The clinical treatment of ESC also refers to the treatment model of HGSOC. The PARP inhibitor niraparib used in this study, which was approved by FDA for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy on March 27, 2017. The homologous recombination related gene mutations in total endometrial cancer accounted for 22%. Homologous Recombination Repair Defect (HRD) +ARID1A accounted for 48%, and 53% of endometrial cancer cell lines were sensitive to PARP inhibitors. The incidence of HRD in endometrial cancer with high copy number (the pathological type is mainly ESC) is 50%, suggesting potential clinical applications of PARP inhibitors for the treatment of ESC.
• Women aged 18 or above
• Histological confirmation of serous endometrial cancer or other types of endometrial cancer
• FIGO stage III-IV
• ESC Patients have received at least 6 cycles of first-line platinum containing chemotherapy after surgery and achieved CR, PR or SD; ESC patients have received platinum containing chemotherapy after the first relapse and achieved CR, PR or SD; these two types of patients are enrolled in cohort 1 and receive niraparib alone as maintenance therapy within 12 weeks after the last chemotherapy treatment.
• ESC Patients have received \>2 lines of platinum containing chemotherapy and relapsed; patients with other types of endometrial cancer have received \>2 lines of platinum containing chemotherapy and have BRCA mutation or be defined as HRD positive; these 2 types of patients are enrolled in cohort 2 and receive niraparib monotherapy.
• Radiotherapy or endocrine therapy history is allowed
• Cohort 1 life expectancy\> 6 months; Cohort 2 life expectancy\> 4 months
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Patients agreed to provide blood samples for testing BRCA status and HRR mutations.
• Patients agreed to provide formalin-fixed and paraffin-embedded tumor tissue samples for the detection of homologous recombination repair related genes (optional)
• Laboratory criteria are as follows:
• Neutrophil count ≥1500/µL;Platelets ≥100,000/µL;Hemoglobin ≥10g/dL;Serum creatinine ≤1.5 times of the upper limit, or creatinine clearance ≥60mL/min;Total bilirubin ≤1.5 times of the upper limit or direct bilirubin ≤1.0 times of the upper limit;AST and ALT ≤2.5 times of the upper limit, and must be ≤5 times of the upper limit of when liver metastasis exists.
• Patients of reproductive potential must have a negative urinary or serum pregnancy test when done and promise to take effective contraceptive measuresduring the period of the study; Or without potential fertility, defined as:
• Women who have undergone contraceptive operation(hysterectomy, bilateral oophorectomy or bilateral salpingectomy), or
• over 60 years old, or≥40 and \<60 years of age, menopause for more than 12 months, and follicle-stimulating hormone test results are within the reference range of research institutions after menopause
• Willingness to sign a written informed consent document and follow the plan
• Any previous toxic and side effects of chemotherapy have recovered to ≤ CTCAE level 1 or baseline level, except for sensory neuropathy or hair loss with stable symptoms ≤ CTCAE level 2