A Phase II, Randomized, Controlled Study to Assess the Efficacy and Safety of Fruquintinib Plus Capecitabine Versus Bevacizumab Plus Capecitabine as Maintenance Treatment Following First-line Chemotherapy for Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- Progression Free Survival
研究概览
简要总结
This is an open-label, multicenter, randomized phase 2 study evaluating the efficacy and safety of fruquintinib plus capecitabine versus bevacizumab plus capecitabine as maintenance therapy following first-line treatment for metastatic colorectal cancer. Patients who have already achieved disease control (including CR/PR and SD), without discontinuation for toxicity, and are progression free after 4-6 months of standard first-line induction treatment will be assigned to 2 maintenance treatment groups by randomization in a 1:1 ratio to receive fruquintinib + capecitabine (Arm A) or bevacizumab + capecitabine (Arm B). The study contains a safety lead-in phase in which the safety and tolerability of fruquintinib + capecitabine will be assessed prior to the phase 2 portion of the study. All patients from Arm A and Arm B will be treated until progressive disease, death from any cause, unacceptable toxicity or informed consent withdrawal (whichever occurs earlier).
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
- None
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
- •18-75 years old (including 18 and 75) at the time of signing the informed consent;
- •Patients who have been histologically or cytologically confirmed adenocarcinoma of the colon or rectum (stage IV);
- •Patients who have achieved disease control (including CR/PR and SD) after 4-6 months of first-line standard chemotherapy (FOLFOX, FOLFIRI, XELOX ± targeted therapy) and are progression free at the start of maintenance therapy;
- •At least one measurable metastatic lesion(s) as defined by RECIST version 1.1;
- •ECOG performance status of 0-1;
- •Body weight ≥40Kg;
- •Life expectancy≥3 months;
- •Adequate organ and bone marrow functions:
- •Neutrophils >1.5×109/L, platelets >100×109/L, and hemoglobin >9 g/dL; Total bilirubin <1.5×upper limit of normal (ULN); aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and/or alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) <2.5×ULN (<5×ULN in case of liver metastases); Creatinine clearance (calculated according to Cockcroft and Gault) ≥50 mL/min; Urinary protein / creatinine ratio < 1 (or urine analysis < 1 + or 24-hour urinary protein < 1g / 24 h);
- •Able to take oral medication;
- •Women of childbearing age must have a negative pregnancy test within the first day of the study, and contraceptive methods should be taken during the study until 6 months after the last administration;
- •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedure.
排除标准
- •Pregnant or lactating women;
- •Any factors that influence the usage of oral administration;
- •Those who have been proved to be allergic to fruquintinib and / or its excipients;
- •Blood transfusion was performed within 1 week before randomization;
- •Non-controlled hypertension after monotherapy, that is, systolic blood pressure > 140mmHg or diastolic blood pressure > 90mmHg;
- •Intercurrence with one of the following: coronary artery disease, arrhythmia and heart failure;
- •Clinically significant electrolyte abnormality;
- •Proteinuria ≥ 2+ (1.0g/24hr);
- •Previous treatment with VEGFR inhibition;
- •Evidence of CNS metastasis;
- •Severe intolerance to capecitabine or 5-FU;
- •Disability of serious uncontrolled intercurrence infection;
- •Uncontrolled hemorrhage in GI;
- •Have evidence or a history of bleeding tendency within two months of the enrollment;
- •Abdominal fistula or gastrointestinal perforation occurred within 6 months before the first treatment, unless repaired by surgery;
- •Within 12 months before the first treatment occurs artery/venous thromboembolic events, such as cerebral vascular accident (including stroke and transient ischemic attack) , etc.;
- •Within 6 months before the first recruitment occurs acute myocardial infarction, acute coronary syndrome or CABG;
- •Incomplete healing of skin trauma, surgical site, wound site or severe mucosal ulcer. Bone fracture or wounds that was not cured for a long time;
- •APTT and /or PT >1.5×ULN;
- •Clinically detectable secondary primary malignancies at the time of enrollment, or had other malignancies in the past 5 years (excluding fully treated basal cell carcinoma of the skin or carcinoma in situ of the cervix);
- •Patients who are not suitable for the study judged by the researchers.
研究组 & 干预措施
Arm A
Maintenance therapy with Fruquintinib Plus Capecitabine
干预措施: Fruquintinib Plus Capecitabine (Drug)
Arm B
Maintenance therapy with Bevacizumab Plus Capecitabine
干预措施: Bevacizumab Plus Capecitabine (Drug)
结局指标
主要结局
Progression Free Survival
时间窗: From Baseline to primary completion date, about 2 years
Progression-free survival is determined from the date of treatment to PD or death from any cause
次要结局
- Overall Survival(From Baseline to primary completion date, about 2 years)
- Adverse Events and Serious Adverse Events(From Baseline to primary completion date, about 2 years)
- QoL(From Baseline to primary completion date, about 24 months)
研究者
Ying Yuan, MD
Professor
Second Affiliated Hospital, School of Medicine, Zhejiang University