A Randomized, Open-label, Parallel Controlled, Multi-center Phase III Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy as First-line Treatment in Subjects With RAS/BRAF Wild Metastatic Colorectal Cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 748
- 试验地点
- 92
- 主要终点
- Progression Free Survival (PFS) assessed by IRC
研究概览
简要总结
This is an open label, randomized, phase Ⅲ study to treat subjects with RAS/BRAF wild-type, unresectable metastatic colorectal cancer. The patients will be randomized into two arms consist of Anlotinib (3 weeks/cycle) + CapeOx and Bevacizumab (3 week/cycle) + CapeOx at a ratio of 1:1. This study is conducted to assess the efficacy and safety of Anlotinib and Chemotherapy as first-line treatment in subjects with RAS/BRAF wild-type Metastatic Colorectal Cancer.
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
- •1. Understood and Signed an informed consent form.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1；Life expectancy≥ 3 months.
- •3. Histologically or cytologically confirmed unresectable metastatic colorectal cancer.
- •4. Has RAS/BRAF wild-type.
- •Has at least one measurable lesion.
- •Adequate organ function. 7.Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ; No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.
排除标准
- •1.Has dMMR/MSI-H.
- •Combined with the following diseases or medical history:
- •Previous or co-existing malignancies within 3 years except for cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors；
- •Has many factors that affect the oral administration of drugs；
- •Has Gastrointestinal bleeding or perforation within 4 weeks before the first dose；
- •Has active inflammatory bowel disease within 4 weeks before the first dose；
- •Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage；
- •Patients whose adverse events (except hair loss) caused by previous treatment did not recover to ≤CTCAE 1 degree；
- •Has received major surgical procedure、biopsy or obvious traumatic injury within 28 days before the first dose；
- •Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary of blood vessels is unclear；
- •Has any bleeding event or the level of bleeding events ≥ CTCAE 3；
- •Has unhealed wounds, ulcerative or fractures；
- •Has arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism；
- •Has a history of psychotropic substance abuse and are unable to quit ；
- •Has any severe and / or uncontrolled disease； 3.Tumor related symptoms and treatment
- •Has received chemotherapy, surgery, radiotherapy, and other anti-cancer therapy within 4 weeks before the first dose.
- •Has received anti-tumor Chinese patent medicine which were approved by NMPA Within 2 weeks before the first dose.
- •Previous adjuvant therapy containing anti-vascular or anti-EGFR targeted drugs.
- •Has received systematic treatment for advanced colorectal cancer.
- •Has symptomatic brain metastases or control of symptoms < 2 month. 4.Has participated in other anticancer drug clinical trials within 4 weeks. 5.According to the judgement of the researchers, there are other factors that may lead to the termination of the study.
研究组 & 干预措施
Anlotinib + CapeOx
Anlotinib combined with CapeOx(Oxaliplatin+Capecitabine) were used for 4-8 cycles, each cycle is 3 weeks. After 8 cycles, the regimen is changed to Anlotinib combined with Capecitabine.
干预措施: Anlotinib hydrochloride capsule (Drug)
Anlotinib + CapeOx
Anlotinib combined with CapeOx(Oxaliplatin+Capecitabine) were used for 4-8 cycles, each cycle is 3 weeks. After 8 cycles, the regimen is changed to Anlotinib combined with Capecitabine.
干预措施: Oxaliplatin (Drug)
Anlotinib + CapeOx
Anlotinib combined with CapeOx(Oxaliplatin+Capecitabine) were used for 4-8 cycles, each cycle is 3 weeks. After 8 cycles, the regimen is changed to Anlotinib combined with Capecitabine.
干预措施: Capecitabine (Drug)
Bevacizumab + CapeOx
Bevacizumab combined with CapeOx(Oxaliplatin+Capecitabine) were used for 4-8 cycles, each cycle is 3 weeks. After 8 cycles, the regimen is changed to Bevacizumab combined with Capecitabine.
干预措施: Bevacizumab (Drug)
Bevacizumab + CapeOx
Bevacizumab combined with CapeOx(Oxaliplatin+Capecitabine) were used for 4-8 cycles, each cycle is 3 weeks. After 8 cycles, the regimen is changed to Bevacizumab combined with Capecitabine.
干预措施: Oxaliplatin (Drug)
Bevacizumab + CapeOx
Bevacizumab combined with CapeOx(Oxaliplatin+Capecitabine) were used for 4-8 cycles, each cycle is 3 weeks. After 8 cycles, the regimen is changed to Bevacizumab combined with Capecitabine.
干预措施: Capecitabine (Drug)
结局指标
主要结局
Progression Free Survival (PFS) assessed by IRC
时间窗: Baseline up to 15 months
PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.
次要结局
- Progression free survival (PFS)(Baseline up to 15 months)
- Overall survival (OS)(Baseline up to 20 months)
- Objective Response Rate（ORR）(Baseline up to 15 months)
- Disease Control Rate (DCR)(Baseline up to 15 months)
- Duration of Response (DOR)(Baseline up to 15 months)