The Effect and Safety on Unresectable CRLM From RFA in Combination With Second-line Chemotherapy and Bevacizumab Compared With the Combination of Second-line Chemotherapy and Bevacizumab: a Randomized and Controlled Clinical Trial
试验速览
- 阶段
- 2 期
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Overall survival (OS), Month
研究概览
简要总结
Basing on the strong evidence from former researches, patients with CRLM can benefit from the treatment of bevacizumab combined with sencond-line chemotherapy. Recently, although with the popularization of RFA, the role that RFA plays in the long term survival of patients with metastatic colorectal cancer (CRC) is still confused. In this designed, randomized, controlled, prospective, and open clinical trial, the effectiveness of RFA combined with second-line chemotherapy + bevacizumab on unresectable CRLM is going to be evaluated compared with that of second-line chemotherapy + bevacizumab. After screened by inclusion and exclusion criteria, the eligible subjects will be randomly allocated into the experimental group-with the treatment of RFA + second-line chemotherapy + bevacizumab and control group-with the treatment of second-line chemotherapy + bevacizumab equally.
详细描述
As a leading cause of death around the world, the mobility and mortality of CRC also increase in china with aging. Currently, distant organ metastasis, most commonly appearing in liver, diminishes the life expectancy in more than 50% of CRC patients. Surgical resection of the tumor primaries and metastases has been the first choice of patients with CRLM with five-year survival rate of 44.2%. With only 25% resectable CRLM, however, most patients lose the operation chance at diagnosis.
In the past two decades, RFA in CRLM treatment has been gradually approved and showed great value in clinic. According to some retrospective researches, for small metastases, the effectiveness of RFA is not inferior to surgery. However, what really makes sense is to ensure if patients with unresectable metastases could benefit from RFA. The results from some former researches and CLOCC study in 2017 noticeably reflected that RFA enabled to prolong the survival significantly in unresectable CRLM patients, which determined its essential role in clinical application.
As a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), bevacizumab shows great potential in tumor therapy: pruning the tumor vessels rapidly by blocking VEGF signaling pathway; straightening and normalizing tumor vessels which ensure the effective perfusion of chemotherapeutics. In addition, depending on durable angiogenesis inhibition, bevacizumab restrains tumor growth and metastasis. To date, bevacizumab combined with chemotherapy is approved in metastatic CRC treatment.
For long term survival, patients with CRLM can benefit from bevacizumab combined with sencond-line chemotherapy basing on the strong evidence from above researches. While the role that RFA plays in this therapeutic regimen is still confused. In this designed clinical trial, the main purpose is to evaluate the effectiveness of RFA combined with second-line chemotherapy + bevacizumab on CRLM patients plans, which is expected to polish up the clinical treatment approaches.
This study is a randomized, controlled, prospective, open, and two-center clinical experiment for patients with metastatic CRC. After screened by inclusion and exclusion criteria, the eligible subjects will be randomly allocated into the experimental group and control group equally. Liver biopsy or specimens of liver metastases are required in all eligible patients for the second pathologic diagnosis by pathology department in Nanfang hospital, Southern Medical University.
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
- 16 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.CRLM patients with histopathological diagnosis. 2.Tumor progression after first-line therapy or intolerable adverse events occur;
- •The first-line therapy should be the standard regimen recommended by NCCN guideline.
- •Tumor progression indicates: progression occurs during the process or within three months after the final treatment of first-line therapy; progression occurs during the period of adjunctive therapy/neoadjuvant therapy or within six months after adjunctive therapy finished.
- •Prior treatment with bevacizumab or cetuximab is allowed. 3.Aged between 16-80 years old (16 and 80 years old are included), with no limitation of gender; 4.ECOG scores 0-1; 5.At least one measurable liver metastasis according to RECIST 1.1 criteria; 6.The liver metastasis is no larger than 50% of total liver lesions; 7.Determined as unresectable liver metastasis by the multidisciplinary team consisting of liver surgeons and medical oncologists;
- •R0 resection cannot be operated on liver metastases. 2)Hepatic artery or the branches of portal vein is invaded. 3)The three main hepatic veins are surrounded by liver metastases. 4)Extrahepatic metastases coexist. 8.Life expectancy is above three months; 9.With full appreciation, voluntary and a signed informed consent; 10.Vital organs with normal function:
- •Routine blood test: hemoglobin (HGB) 85g/L, platelet (PLT) 80/L, and neutrophils 1.5/L;
- •Normal coagulation function originally or after treatment (if exceeding reference level, whether it is still within normal range should be determined by researchers);
- •Total bilirubin(BIL) is 1.5 times higher than the upper normal limit, alanine aminotransferase (ALT) and aspartic transaminase (AST) are 5 times higher than the upper normal limit;
- •Urine protein ranges from - to +, and serum creatinine 1.5×ULN; 11.Negative pregnancy test results in women of childbearing age (7 days before RFA treatment), and effective contraceptive measures must be adopted until 6 m after the last treatment.
排除标准
- •Prior treatment with other clinically experimental drugs, systemic chemotherapy, immunotherapy or targeted therapy within 2 weeks before this trial;
- •Prior treatment on liver metastases with radiotherapy, hepatic arterial infusion chemotherapy, transcatheter hepatic arterial chemoembolization, cryoablation, microwave ablation or RFA within 2 weeks before this trial;
- •Abnormal coagulation function and with hemorrhagic tendency;
- •Damaged or infectious skin in the puncture or electrode sticking area;
- •Complicated by active hepatitis or hepatic failure;
- •Complicated by severe hypertension or hypertensive crisis (systolic pressure 180 mmHg and/or diastolic pressure 110 mmHg in a resting state);
- •Impaired cardiac function, manifested as left ventricular ejection fraction 50%, severe arrhythmia, unstable angina, history of myocardial infarction within 1 year before this trial, or congestive heart-failure in NYHA class III or IV;
- •History of stroke within 6 months;
- •History of other malignancies except for colorectal cancer within 5 years;
- •Abnormal medical or psychologic status that may hamper the ongoing trial or signing an informed consent;
- •No or limited legal capacity;
- •Pregnant or breast-feeding women;
- •Combined acute infection or human immunodeficiency virus (HIV) infection;
- •With contradictions for bevacizumab; 1)History of severe hemorrhage or hemoptysis 1 month before this trial 2)Urine protein 2+, and 24-hour urinary protein quantitative 2g 3)Allergy to bevacizumab or any active ingredients 4)Patients with surgery, major trauma or fracture within 4 weeks 5)Unhealed wounds, intestinal stomas or peptic ulcer
- •Treated with other experimental antineoplastic drugs.
研究组 & 干预措施
The control Arm
bevacizumab and second-line chemotherapy
干预措施: Bevacizumab and second-line chemotherapy (Drug)
The experimental Arm
RFA, bevacizumab and second-line chemotherapy
干预措施: RFA, bevacizumab and second-line chemotherapy (Combination Product)
结局指标
主要结局
Overall survival (OS), Month
时间窗: From the date of randomization until the date of death due to any cause, assessed up to 36 months
次要结局
- Progress free survival (PFS), Month(From the date of randomization until the date of first documented tumor progression or date of death before progression due to any cause, assessed up to 36 months)
- Time to progression (TTP), Month(From the date of randomization until the date of first documented tumor progression, assessed up to 36 months)
研究者
Wangjun Liao
Chief of Oncology Department
Nanfang Hospital, Southern Medical University