CapeOX Combined With Bevacizumab Plus Anti-PD1 Antibody as Neoadjuvant Therapy for Locally Recurrent Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Objective response rate
研究概览
简要总结
This prospective, single-arm study aims to investigate the efficacy and safety of CapeOX combined with Bevacizumab plus Anti-PD1 Antibody as neoadjuvant therapy for locally recurrent colorectal cancer
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary colorectal cancer underwent radical surgery, histologically confirmed as adenocarcinoma and achieved R0 resection, and postoperative adjuvant chemotherapy with Xelox or other first-line standard regimens.
- •Based on the imaging and histological examination results, the patient was clinically assessed and diagnosed with locally recurrent colorectal adenocarcinoma.
- •The patients did not receive any treatment, including chemotherapy, targeted therapy, immunotherapy, or radiotherapy, within the past month.
- •Measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria.
- •Eastern Cooperative Oncology Group (ECOG) 0-
- •Absence of distant metastasis confirmed by CT, MRI or PET/CT.
- •Adequate hematologic and organ function, defined by protocol-specified laboratory test results, obtained within 7 days before first dose. Absolute neutrophil count ≥1500/mm3, platelet ≥100,000/mm3, Hb ≥10g/dl, serum creatinine ≤1.5 times ULN, creatinine clearance rate ≥50mL/min, ALT and AST ≤2.5 times ULN, INR or aPTT ≤1.5 times ULN (INR ≤2 times ULN and aPTT in normal range for patients who are on prophylactic anticoagulant therapy within 14 days before study treatment), total bilirubin level ≤2 times ULN (within 7 days before study treatment).
- •Women of childbearing age should confirm that serum pregnancy test is negative and agree to use effective contraceptive methods during study treatment and the following 60 days.
- •Life expectancy> 3 months
- •Signed and written informed consent
排除标准
- •Previously received anti-PD1 or anti-PDL1 or anti-PDL2 or anti-CTLA
- •Intestinal obstruction or uncontrollable active bleeding caused by the tumor requiring urgent treatment.
- •Contraindications of Oxaliplatin, Capecitabine, Bevacizumab, and Tislelizumab.
- •Hypersensitivity to other monoclonal antibodies.
- •Any active, known or suspected autoimmune disease.
- •Uncontrolled pleural effusion, pericardial effusion, or ascites to a moderate or greater extent.
- •History of one of the following diseases: idiopathic pulmonary fibrosis, organized pneumonia (eg. bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia and interstitial pneumonia, or evidence of active pneumonia through enhanced chest CT screening.
- •Major surgery within 4 weeks before enrollment and haven't fully recovered from the previous surgery.
- •Active bleeding or abnormal coagulation (aPTT >43s or INR >1.5 times ULN), or having a tendency to bleed or receiving thrombolytic or anticoagulant therapy.
- •Previously received allogeneic stem cell or parenchymal organ transplantation.
- •Any significant clinical or laboratory abnormality that the investigator considers to influence the safety assessment, eg. uncontrolled active infection, uncontrolled diabetes, hypertension that cannot be reduced to normal range with monotherapy, grade II or above peripheral neuropathy, congestive heart failure, heart disease (class II or higher) as defined by the New York College of Cardiology, myocardial infarction within 3 months prior to enrollment, unstable arrhythmias, unstable angina pectinis, chronic kidney disease, abnormal thyroid function and previous or co-existing malignancies.
- •History of uncorrected serum electrolyte disturbances such as potassium, calcium and magnesium.
- •HIV infection.
- •Active hepatitis B or hepatitis C.
- •Pregnancy or lactation period, or unwilling to use contraception during the trial.
- •With other malignancy within 5 year, except cervical carcinoma in situ, basal or squamous skin cancer, local prostatic carcinoma and ductal carcinoma in situ.
- •Use corticosteroids (dose of prednisone or similar drugs> 10mg/day) or other immunosuppressive agents within 14 days before enrollment.
- •Patients with active tuberculosis (TB) who are receiving anti-TB treatment or have received anti-TB treatment within 1 year.
- •Active infection, or treatment with oral or intravenous antibiotics within the first 2 weeks prior to neoadjuvant therapy, except prophylactic administration.
- •Anti-infective vaccine (eg. influenza vaccine, varicella vaccine, etc.) injection within 4 weeks before neoadjuvant therapy.
- •Previous participation in other clinical trials within 4 weeks before neoadjuvant therapy.
- •Any other disease, metabolic disorder, abnormal physical examination or abnormal laboratory results that may constrain the use of trial drug, or affect the reliability of study results, or lead to high risk of treatment complications, or affect patient compliance.
研究组 & 干预措施
CapeOx+ Bevacizumab + Tislelizumab as neoadjuvant treatment
CapeOx: Capecitabine is given orally at 1000mg / m² twice a day from day1-14 every 3 weeks for 4 cycles and Oxaliplatin is given by intravenous infusion at 130mg / m² on Day 1 every 3 weeks for 4 cycles; Bevacizumab：Bevacizumab is given intravenously at 7.5mg/kg on day 1 every 3 weeks for 4 cycles; Tislelizumab：Tislelizumab is given intravenously at 200 mg on day 1 every 3 weeks for 4 cycles
干预措施: Capecitabine (Drug)
CapeOx+ Bevacizumab + Tislelizumab as neoadjuvant treatment
CapeOx: Capecitabine is given orally at 1000mg / m² twice a day from day1-14 every 3 weeks for 4 cycles and Oxaliplatin is given by intravenous infusion at 130mg / m² on Day 1 every 3 weeks for 4 cycles; Bevacizumab：Bevacizumab is given intravenously at 7.5mg/kg on day 1 every 3 weeks for 4 cycles; Tislelizumab：Tislelizumab is given intravenously at 200 mg on day 1 every 3 weeks for 4 cycles
干预措施: Oxaliplatin (Drug)
CapeOx+ Bevacizumab + Tislelizumab as neoadjuvant treatment
CapeOx: Capecitabine is given orally at 1000mg / m² twice a day from day1-14 every 3 weeks for 4 cycles and Oxaliplatin is given by intravenous infusion at 130mg / m² on Day 1 every 3 weeks for 4 cycles; Bevacizumab：Bevacizumab is given intravenously at 7.5mg/kg on day 1 every 3 weeks for 4 cycles; Tislelizumab：Tislelizumab is given intravenously at 200 mg on day 1 every 3 weeks for 4 cycles
干预措施: Bevacizumab (Drug)
CapeOx+ Bevacizumab + Tislelizumab as neoadjuvant treatment
CapeOx: Capecitabine is given orally at 1000mg / m² twice a day from day1-14 every 3 weeks for 4 cycles and Oxaliplatin is given by intravenous infusion at 130mg / m² on Day 1 every 3 weeks for 4 cycles; Bevacizumab：Bevacizumab is given intravenously at 7.5mg/kg on day 1 every 3 weeks for 4 cycles; Tislelizumab：Tislelizumab is given intravenously at 200 mg on day 1 every 3 weeks for 4 cycles
干预措施: Tislelizumab (Drug)
结局指标
主要结局
Objective response rate
时间窗: 15 weeks
Percentage of patients who achieve partial response (PR) or complete response (CR)
R0 resection rate
时间窗: 15 weeks
Percentage of patients who achieve R0 resection
Pathological complete response rate
时间窗: 15 weeks
Percentage of patients who achieve pathological complete response (pCR) based on local investigator
Tumor regression grade (TRG)
时间窗: 15 weeks
Incidence of Treatment-Related Adverse Events
时间窗: Until 30 days after the last treatment
Number of adverse events
次要结局
- Surgical complications(Until 90 days after surgery)
- Quality of life score (QoL score)(Until 30 days after the last treatment)
- Event free survival(Up to 3 years)
- Disease-free survival(Up to 3 years)
- One-year or two-year disease-free survival rate(Up to 2 years)
- One-year or two-year overall survival rate(Up to 2 years)