A Randomized, Double-blind, Placebo-controlled, Multi-center Phase II Clinical Trial to Evaluate the Efficacy and Safety of Fruquintinib Plus Best Supportive Care in Patients With Advanced Non-squamous Non-small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 91
- 试验地点
- 12
- 主要终点
- Progressive free survival (PFS)
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, multi-center Phase II clinical trial to evaluate the efficacy and safety of Fruquintinib plus best supportive care in patients with advanced non-squamous non-small cell lung cancer who failed to second-line standard chemotherapy.
详细描述
Approximately 90 subjects will be randomized to Fruquintinib plus best supportive care or placebo plus best supportive care at a 2:1 ratio.
Randomization will be stratified by EGFR (epidermal growth factor receptor) gene status: mutant vs. wild type vs. unknown.
All subjects will receive Fruquintinib/placebo for consecutive 3 weeks, followed by one-week rest. A treatment cycle consists of 4 weeks. Tumor assessment will be performed every 4 weeks in the first 3 cycles, and every 8 weeks since the 4th cycle, until disease progression. Further treatment and survival follow-up after progression will be recorded.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Fully understand the study and sign the informed consent form voluntarily;
- •Histologically and/or cytologically diagnosed with local advanced and/or metastatic stage IIIB/IV non-squamous NSCLC;
- •Previously failed to two chemotherapy regimens(treatment failure is defined as disease progression or intolerable toxicity), patients with positive EGFR mutation permitted to treated by EGFR-TKI previously; patients with EGFR wild type or unknown whether or not treated by EGFR-TKI previously;
- •Aged 18-75 years (inclusive);
- •Body weight ≥40 kg;
- •Evident measurable lesion(s) (according to RECIST1.1);
- •ECOG Performance Status 0-1;
- •Expected survival >12 weeks
排除标准
- •Treatment in another clinical trials in the past 3 weeks; or treatment with systemic anti-tumor chemotherapy, radiotherapy or biotherapy within 3 weeks prior to administration of the study drug;
- •Previous therapy with VEGF/VEGFR inhibitors;
- •Unrecovered from toxicity caused by previous anti-cancer treatment (CTCAE >grade 1), or not completely recovered from previous surgery;
- •Previous active brain metastasis (without radiotherapy previously, or symptoms stable < 4 weeks, or with clinical symptoms, or with medication to control symptoms);
- •Other malignancies except basal cell carcinoma or cervical carcinoma in situ in the past 5 years;
- •Uncontrolled clinical active infection, e.g. acute pneumonia and active hepatitis B;
- •Dysphagia or known drug malabsorption;
- •Present active duodenal ulcer, ulcerative colitis, intestinal obstruction and other gastrointestinal diseases or other conditions that may lead to gastrointestinal bleeding or perforation according to the investigators' judgment; or with a history of intestinal perforation or intestinal fistula;
- •Have evidence or a history of thrombosis or bleeding tendency, regardless of seriousness;
- •Stroke and/or transient ischemic attack within 12 months prior to enrollment;
- •Appropriate organ function. Patients with any of the following conditions will be excluded:
- •Absolute neutrophil count (ANC) <1.5×109/L, platelet <100×109/L or hemoglobin <9 g/dL within 1 week prior to enrollment;
- •Serum total bilirubin >1.5 upper limit of normal (ULN), alanine transaminase and aspartate transferase >1.5×ULN; ALT and AST > 3×ULN in patients with liver metastasis;
- •Electrolyte abnormality of clinical significance;
- •Blood creatinine >ULN and creatinine clearance <60 ml/min;
- •Urine protein 2+ or above, or 24 h urine protein quantification ≥1.0 g/24 h;
- •Activated partial thromboplastin time (APTT) or/and INR and prothrombin time (PT) >1.5×ULN (according to reference range in each clinical study center);
- •Uncontrolled hypertension, systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg with medication; or heart failure NYHA classification ≥ grade 2;
- •Heart function evaluation: left ventricular ejection fraction <50% (echocardiography);
- •Acute myocardial infarction, severe/unstable angina or coronary bypass surgery within 6 months prior to enrollment; history of arterial thrombosis or deep venous thrombosis;
- •Skin wound, surgical site, wound site, severe mucosal ulcer or fracture without complete healing;
- •Female subjects who are pregnant or lactating or of child bearing potential with positive pregnancy test result before the first dose;
- •Patients with child bearing potential who or whose sexual partners are not willing to take contraceptive measures;
- •Any clinical or laboratory abnormalities unfit to participate in this clinical trial according to the investigator's judgment;
- •Serious psychological or psychiatric disorders which may affect subject compliance in this clinical study;
- •Allergy to Fruquintinib and/or excipient contained in trial drugs.
研究组 & 干预措施
Control Group
Placebo is a capsule in the form of 1mg and 5 mg, orally, once daily, 3 weeks on/1week off with best supportive care.
干预措施: Placebo (Drug)
Treatment Group
The subjects will receive oral Fruquintinib at fasting state 5mg+best supportive care, once daily for the first 3 consecutive weeks and dose holiday for 1 week according to their dose regimens until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent
干预措施: Fruquintinib (Drug)
结局指标
主要结局
Progressive free survival (PFS)
时间窗: measured every 4 weeks at first 2 cycles and every 8 weeks since the third cycle from randomization to disease progression, assessed up to one year
To compare the Progressive Free Survival (PFS) of Fruquintinib plus best supportive care (BSC) versus placebo plus BSC in patients advanced non-squamous NSCLC patients who failed to standard second-line chemotherapy according to RECIST 1.1
次要结局
- Overall survival (OS)(every 2 months from randomization to death, assessed up to one year)
- Objective response rate (ORR)(measured every 4 weeks at first 2 cycles and every 8 weeks since the third cycle from randomization to disease progression, assessed up to one year)
- Disease control rate (DCR)(measured every 4 weeks at first 2 cycles and every 8 weeks since the third cycle from randomization to disease progression, assessed up to one year)
- safety and tolerability by incidence, severity and outcome of adverse events(From randomization to 30 days after last dose)