A Phase I/II Study of Irinotecan, Oxaliplatin, Capecitabine (XELOXIRI) and Bevacizumab as a First-line Therapy for Patients With Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 入组人数
- 106
- 试验地点
- 2
- 主要终点
- maximum tolerated dose (MTD)
研究概览
简要总结
The phase I/II study was designed to evaluate if the regimen of Irinotecan, Oxaliplatin, Capecitabine (XELOXIRI) and Bevacizumab is a superior first-line option for patients with metastatic colorectal cancer(mCRC) in terms of safety and efficacy.
详细描述
Recent studies have shown that the triplet-drug regimen FOLFOXIRI (irinotecan/oxaliplatin/fluorouracil) can further improves survival benefit for patients with metastatic colorectal cancer(mCRC) compared to standard two-drug regimens in first-line therapy, especially when combined with bevacizumab. However, the increased toxicities of FOLFOXIRI limited its usage. Capecitabine demonstrates a superior efficacy and safety than fluorouracil, so we designed this trial to evaluate if the XELOXIRI plus bevacizumab can be a better alternative to FOLFOXIRI plus bevacizumab. The phase I study is to determine the safety and the recommended phase II dose (RP2D) of XELOXIRI plus Bevacizumab. In the phase II study, we aim to determine the efficacy of the regimen as first-line therapy for mCRC and explore potential molecular biomarkers (genomes, circulating tumor cell) for toxicity forecasting or efficacy monitoring.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically confirmed metastatic colorectal adenocarcinoma;
- •Age 18-80 years old;
- •Eastern Cooperation Oncology Group (ECOG) performance score(<2);
- •At least one measurable lesion for disease assessment according to RECIST version 1.1;
- •Able to take oral medications;
- •Previous fluoropyrimidine-based adjuvant or neoadjuvant chemotherapy was allowed only when it ended ≥ 6 months before study enrollment;
- •No previous therapy for mCRC;
- •Adequate organ functions as assessed by the following laboratory requirements: Leukocytes≥3.0x109/L, absolute neutrophil count≥1.5x109/L, platelet count≥100x109/L, hemoglobin≥9g/dL; serum bilirubin≤1.5x the upper limit of normal(ULN);Alanine aminotransferase(ALT) and aspartate aminotransferase(AST)≤3x ULN; serum creatinine≤1.5x ULN; calculated creatinine clearance or 24 hour creatinine clearance ≥60ml/min.
- •An expected survival of at least 3 months;
- •Willingly provide written informed consent to study procedures.
排除标准
- •Patients with dysphagia, active peptic ulcer, intestinal obstruction, active gastrointestinal bleeding, peptic perforation, malabsorption syndrome or uncontrolled intestinal inflammatory diseases;
- •With a history of extensive enterotomy or pelvic radiation therapy; Suffering from grade 2 or higher symptomatic peripheral neuropathy according to National Cancer Institute Common Toxicity (NCI-CTC) criteria;
- •Uncontrolled central nervous system metastasis, disseminated intravascular coagulation or active infection;
- •With concurrent cancer distinct from colorectal adenocarcinoma except cured skin basal cell carcinoma and cervical carcinoma in situ;
- •Undergone a major operation, open biopsy or major traumatic injury within 28 days before study enrollment or have potential to receive major operation during the trial;
- •Received central venous access device within 2 days before study enrollment;
- •Any kind of concurrent cardiac disease with clinical meanings, such as cardiovascular accident, myocardial infarction, thromboembolism or hemorrhage within 6 months before enrollment, congestive heart failure ≤New York Heart Association (NYHA) class 2 or uncontrolled hypertension.
- •With positive urine protein and 24-hour urinary protein content>1g;
- •Have a tendency of bleeding or clotting;
- •With nasty open wounds, ulcers or fractures;
- •Current or recent treatment of anticoagulants, antiplatelet agent or nonsteroidal anti-inflammatory drugs, while aspirin of daily dose less than 325mg is allowed.
- •With any illness or medical conditions that may jeopardize the patient's compliance or interfere the analyses or judgements of study results;
- •Pregnancy or lactation at the time of study entry;
- •With fertility but refuse to contraception.
研究组 & 干预措施
XELOXIRI/Bevacizumab
drugs: Irinotecan, Oxaliplatin, Capecitabine, Bevacizumab bevacizumab 5mg/kg on day1, irinotecan 150mg/m2 or 165mg/m2 on day1, oxaliplatin 85mg/m2 on day1 and capecitabine 1000mg/m2 twice a day on day1-7, administered every 2 week for 12 cycles, after 12 cycles, administer bevacizumab 5mg/kg on day 1 and capecitabine 1000mg/m2 twice a day on day1-7 as maintenance therapy.
干预措施: XELOXIRI/Bevacizumab (Drug)
结局指标
主要结局
maximum tolerated dose (MTD)
时间窗: up to 1 year
MTD is determined according to the DLT in the phase I study
objective response rate (ORR)
时间窗: up to 2 years
ORR is defined as the proportion of patients achieving complete response or partial response
dose-limited toxicity (DLT)
时间窗: up to 1 year
dose limited toxicities are evaluated in the phase I study according to CTCAE v5.0 and reviewed through the phase I study completion
recommended phase 2 dose (RP2D)
时间窗: up to 1 year
RP2D is determined according to DLT and MTD in the phase 1 study
次要结局
- the surgical resection rate of patients with liver-only metastases(up to 2 years)
- time to response (TTR)(up to 2 years)
- overall survival (OS)(up to 5 years)
- disease control rate (DCR)(up to 2 years)
- Adverse events (AEs)(though study completion, an average of 2 years)
- progression-free survival (PFS)(though study completion, an average of 2 years)
- duration of response (DOR)(though study completion, an average of 2 years)
研究者
Lin Yang
professor
Chinese Academy of Medical Sciences