Efficacy and Safety of Niraparib Combined With Bevacizumab in Platinum Refractory/Resistant Recurrent Ovarian Cancer
Efficacy and Safety of Niraparib Combined With Bevacizumab in Platinum Refractory/Resistant Recurrent Ovarian Cancer
Niraparib is an oral, potent and highly selective PARP1/2 inhibitor. It can be used as a
 single drug in HRD positive ovarian cancer patients for multi-line therapy. Bevacizumab is a
 recombinant humanized monoclonal antibody that inhibits tumor angiogenesis and is also
 recommended for the treatment of recurrent ovarian cancer. Clinical studies showed that
 niraparib combined with bevacizumab could significantly prolong progression free survival of
 platinum sensitive recurrent ovarian cancer. We intend to conduct a single-arm, prospective,
 open-label, phase II study to observe the efficacy and safety of niraparib combined with
 bevacizumab in the treatment of FIGO III/IV platinum refractory/resistant ovarian cancer,
 fallopian tube cancer and primary peritoneal cancer. The results are expected to provide more
 effective and precise treatment for platinum resistant recurrent/refractory ovarian cancer
 patients.
The study is a single-arm, prospective, open-label, phase II study to observe the efficacy
 and safety of niraparib combined with bevacizumab in the treatment of FIGO III/IV platinum
 refractory/resistant ovarian cancer, fallopian tube cancer and primary peritoneal cancer.The
 primary end point is the objective response rate, and the secondary end points are
 progression free survival, duration of remission, disease control rate and safety. We also
 stratified analysis the level of tumor load, the status of BRCA and HRD on the efficacy and
 safety.
Inclusion Criteria:

 1. Subjects understand the trial process, sign informed consent, agree to participate in
 the study, and have the ability to follow the protocol;

 2. Participant must be female ≥18 years of age;

 3. Histologically confirmed FIGO stage III or IV ovarian cancer, fallopian tube cancer,
 or primary peritoneal cancer;

 4. Participants must have high-grade serous or endometrioid histology;

 5. Subjects were initially treated with platinum, and the disease recurrence occurred
 within 6 months after the end of the previous platinum-containing chemotherapy, that
 is, platinum resistance relapsed; Subjects have disease progression during initial
 platinum based chemotherapy defined as platinum refractory;

 6. Patients may have received a PARP inhibitor as first-line maintenance therapy;

 7. Patients may have received bevacizumab though no other prior use of anti-angiogenic
 therapy；

 8. Subjects must have measurable lesions (according to RECIST1.1) and radiologically
 confirmed disease progression at the time of previous treatment; or CA125 elevated for
 two consecutive times and 2.5 times upper the limit of normal value；

 9. Subject agrees to take blood samples for gBRCA mutations, can provide formalin-fixed,
 paraffin-embedded tumor tissue samples for sBRCA and homologous recombination
 deficiency(HRD) detection;

 10. Life expectancy>12 weeks;

 11. Subject's ECOG physical status score is 0-2;

 12. Good organ function, including:Neutrophil
 count≥1500/μL;Platelets≥100,000/μL;Hemoglobin≥10g/dL;Serum creatinine≤1.5 times the
 upper limit of normal value, or creatinine clearance≥60mL/min (calculated according to
 Cockcroft-Gault formula);Total bilirubin≤1.5 times the upper limit of normal value or
 direct bilirubin≤ 1.0 times the upper limit of normal value;AST and ALT≤2.5 times the
 upper limit of normal value. When liver metastases are present, it must be≤5 times the
 upper limit of normal value;

 13. For women with fertility potential, if blood test or urine pregnancy test is negative
 within one week before enrollment, effective contraceptive measures must be taken,
 such as physical barrier contraceptive method (condom) or complete abstinence. Oral,
 injectable or implantable hormonal contraceptives are not allowed. Or women without
 reproductive potential, defined as: I. Natural menopause and menopause for more than 1
 year; II. Surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
 hysterectomy); III. serum follicle-stimulating hormone, luteinizing hormone, and
 plasma estradiol levels were within the menopausal criteria of the research center
 laboratory;

 14. Subject is able to adhere to the protocol;

 15. The adverse effect of any previous chemotherapy have recovered to ≤ Grade1 (CTCAE
 v5.0) or baseline levels, except for sensory neuropathy or hair loss with stable
 symptoms ≤ Grade2 (CTCAE v5.0).

 Exclusion Criteria:

 1. Personnel involved in the formulation or implementation of the research plan;

 2. Patient participated in other clinical trails using other experimental drugs at the
 same time as the study;

 3. People who are known to be allergic to Niraparib or Bevacizumab (or active or inactive
 ingredients of drugs with similar chemical structure);

 4. People who are inability to swallow oral drugs and any gastrointestinal diseases that
 may interfere with the absorption and metabolism of the study drugs, such as
 uncontrollable nausea and vomiting, gastrointestinal obstruction or malabsorption;

 5. Major surgery was performed within 4 weeks before the start of the study or did not
 recover after the operation;

 6. Received palliative radiotherapy of >20% bone marrow 1 week before enrollment;

 7. The subjects had other malignant diseases in past 2 years, except skin squamous cell
 carcinoma, basal-like carcinoma, breast intraductal carcinoma in situ, or cervical
 carcinoma in situ;

 8. Previous or currently diagnosed myelodysplastic syndrome (MDS) or acute myeloid
 leukemia (AML);

 9. Patients with serious and uncontrollable diseases or the general situation of the
 subjects judged by the researchers to be unsuitable for enrolling the study, including
 but not limited to: active viral infection, such as human immunodeficiency virus,
 hepatitis B, hepatitis C, etc.; severe cardiovascular disease, uncontrollable
 ventricular arrhythmia, myocardial infarction in the last three months; uncontrollable
 grand mal epilepsy, Unstable spinal cord compression, superior vena cava syndrome or
 other mental disorders that affect patients to sign the informed consent; hypertension
 beyond drug control; immune deficiency (except splenectomy) or other diseases that
 researchers consider may expose patients to high-risk toxicity;

 10. The previous history of thromboembolism was defined as: uncontrolled pulmonary
 embolism, deep venous thrombosis, and other related conditions after anticoagulant
 therapy for more than 3 months before enrollment;

 11. Any medical history or existing clinical evidence indicates that there may be
 confusion of study results, interference with patients' compliance with the trial
 protocol throughout the study treatment period, or not in the best interests of
 patients;

 12. Receive platelet or red blood cell transfusions within 4 weeks;

 13. Patients who are pregnant or lactation, or who plan to become pregnant during study
 treatment.