An Open-label, Single Arm, Phase II Trial of Niraparib in Combination With Anlotinib in Patients With Platinum-resistant Recurrent Ovarian Cancer, Fallopian Tube Cancer, and Primary Peritoneal Cancer (Ovarian Cancer)
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Objective Response Rate
研究概览
简要总结
At present, the standard treatment for platinum-resistant ovarian cancer patients is platinum-free chemotherapy, with poor efficacy and tolerance. The combination of anti-angiogenic drugs and PARPi can play a synergistic anti-tumor role and achieve good efficacy in platinum-sensitive recurrent ovarian cancer. This study intends to explore the safety and effectiveness of anlotinib and niraparib dual therapy in patients with platinum-resistant recurrent ovarian cancer, fallopian tube cancer, and primary peritoneal cancer (ovarian cancer).
详细描述
The present study is an open, single-center, prospective, single-arm phase II study to investigate the efficacy and safety of nilapalil combined with anrotidine in the treatment of platinum-resistant recurrent ovarian cancer. In this study, 40 histopathologically diagnosed patients with high-grade serous ovarian, fallopian tube and primary peritoneal cancer were treated with neelapalil plus anrotinib in patients who underwent first-line chemotherapy or above and had a recurrence of platinum-resistant chemotherapy (the time of tumor progression of the last platinum-containing chemotherapy < 6 months). The study will be divided into two phases. The first phase will include six patients on a 21-day cycle (nierapalil 200mg QD*21; Anrotidine 12mg qd d1-14, d15-21 suspension), all subsequent patients were enrolled if no more than dose-restricted toxic event occurred within a cycle, and the combination treatment was continued until the disease progressed or the toxicity was intolerable.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Subjects understand the trial process, sign informed consent, agree to participate in the study, and have the ability to follow the protocol;
- •18 ~ 70 years old (inclusive), female;
- •Histologically diagnosed ovarian, fallopian tube, or primary peritoneal cancer;
- •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;
- •Life expectancy > 16 weeks;
- •Patient's ECOG physical status score is 0-1;
- •Subject agrees to take blood samples for gBRCA mutations;
- •Can provide formalin-fixed, paraffin-embedded tumor tissue samples for sBRCA and homologous recombination repair-related genes detection (optional);
- •Good organ function, including:
- •Neutrophil count >= 1500 / μL;
- •Platelets >= 100,000 / μL;
- •Hemoglobin >= 9g / 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.
- •The toxic side effects of any previous chemotherapy have recovered to <= CTCAE level 1 or baseline levels, except for sensory neuropathy or hair loss with stable symptoms <= CTCAE level 2.
排除标准
- •People who are known to be allergic to Niraparib or Anlotinib (or active or inactive ingredients of drugs with similar chemical structure);
- •Symptomatic, uncontrolled brain or pia mater metastases;
- •Underwent major surgery within 3 weeks before the study began or has not recovered after surgery;
- •Received palliative radiotherapy of > 20% bone marrow 1 week before enrollment;
- •Have invasive cancer other than ovarian cancer (except fully treated basal or squamous cell skin cancer) within 2 years before enrollment;
- •Patients with central lung squamous cell carcinoma or at risk for large hemoptysis;
- •Previous or currently diagnosed myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML);
- •Severe or uncontrolled diseases, including but not limited to: uncontrollable nausea and vomiting, inability to swallow or gastrointestinal diseases that may interfere with drug absorption and metabolism; active viral infections; mental illnesses that affect patients' signed informed consent History of bleeding tendency and thrombosis; history of severe cardiovascular disease;
- •Laboratory abnormalities: hyponatremia; hypokalemia; uncontrollable nail function abnormalities;
- •Receive platelet or red blood cell transfusions within 4 weeks;
- •Patients who are pregnant or nursing, or who plan to become pregnant during study treatment;
- •Have previously received any PARP inhibitor treatment.
研究组 & 干预措施
Treatment group
Niraparib 300mg(Body Weigh ≥77 kg)/200mg (Body Weigh <77 kg) po QD day1~21, Anlotinib 12mg po QD day1~14.
Starting dose of anlotinib changed to 10mg from 2020-11-13.
干预措施: Niraparib (Drug)
Treatment group
Niraparib 300mg(Body Weigh ≥77 kg)/200mg (Body Weigh <77 kg) po QD day1~21, Anlotinib 12mg po QD day1~14.
Starting dose of anlotinib changed to 10mg from 2020-11-13.
干预措施: Anlotinib (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: at 6 months
The primary objective of this study is to determine the preliminary efficacy of administration of niraparib in combination with anlotinib in the treatment of platinum-resistant recurrent ovarian cancer, as measured by the objective response rate (ORR), which is a combination of CR (the target lesion completely disappeared over 4 weeks) and PR (Target lesions were reduced by more than 30% for more than 4 weeks).
次要结局
- Progression-free survival(at 6 months)
- Objective tumor response(at 6 months)
- The frequency and severity of adverse events(Baseline through 1 year)
研究者
Jihong Liu
professor
Sun Yat-sen University