Phase II Randomized Study of Maintenance Treatment With Bevacizumab or Bevacizumab Plus Metronomic Chemotherapy After First-line Induction FOLFOXIRI Plus Bevacizumab for Metastatic Colorectal Cancer Patients
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 232
- 试验地点
- 38
- 主要终点
- progression-free survival (PFS)
研究概览
简要总结
This study consist of 4-months induction first-line chemotherapy with the G.O.N.O. FOLFOXIRI regimen plus bevacizumab followed by maintenance with bevacizumab or bevacizumab plus metronomic chemotherapy (with capecitabine and cyclophosphamide) in mCRC patients.
The main objective of this study is to preliminarily evaluate the potential effects of the combination of a metronomic chemotherapy with capecitabine and cyclophosphamide to maintenance bevacizumab on pharmacodynamic and clinical parameters among mCRC patients.
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
- •Histologically proven diagnosis of colorectal cancer.
- •Not resectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
- •At least one measurable lesion according to RECIST criteria.
- •Male or female of 18-75 years of age.
- •ECOG PS < 2 if aged < 71 years, ECOG PS = 0 if aged 71-75 years;
- •Life expectancy of at least 12 weeks.
- •Previous adjuvant chemotherapy containing oxaliplatin is allowed if more than 12 months have elapsed between the end of adjuvant therapy and first relapse;
- •Previous adjuvant chemotherapy with fluoropyrimidine monotherapy is allowed if more than 6 months have elapsed between the end of adjuvant and first relapse;
- •Neutrophils 1.5 x 109/L, Platelets 100 x 109/L, Hgb >9 g/dl.
- •Total bilirubin 1.5 time the upper-normal limits (UNL) of the institutional normal values and ASAT (SGOT) and/or ALAT (SGPT) 2.5 x UNL, or 5 x UNL in case of liver metastases, alkaline phosphatase 2.5 x UNL, 5 x UNL in case of liver metastases.
- •Creatinine clearance >50 mL/min or serum creatinine 1.5 x UNL.
- •Urine dipstick of proteinuria <2+. Patients discovered to have 2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate <1 g of protein/24 hr.
- •Written informed consent to treatment and translational analyses.
排除标准
- •Radiotherapy to any site within 4 weeks before the study.
- •Previous treatment with bevacizumab
- •Untreated brain metastases or spinal cord compression or primary brain tumours.
- •History or evidence upon physical examination of CNS disease unless adequately treated.
- •Symptomatic peripheral neuropathy > 2 grade NCIC-CTG criteria;
- •Serious, non-healing wound, ulcer, or bone fracture.
- •Evidence of bleeding diathesis or coagulopathy.
- •Uncontrolled hypertension.
- •Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication.
- •Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes.
- •Chronic, daily treatment with high-dose aspirin (>325 mg/day).
- •Treatment with any investigational drug within 30 days prior to enrollment.
- •Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of basal and squamous cell carcinoma or cervical cancer in situ.
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study.
- •Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
- •Pregnant or lactating women. Women of childbearing potential with either a positive or no pregnancy test at baseline. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study (barrier contraceptive measure or oral contraception).
研究组 & 干预措施
Maintenance:BEVACIZUMAB
Induction: FOLFOXIRI; Manteinance: Bevacizumab
干预措施: Maintenance:BEVACIZUMAB (Drug)
Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE
Induction: FOLFOXIRI; Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE(Metronomic Chemotherapy)
干预措施: Maintenance:BEVACIZUMAB+CAPECITABINE+CYCLOPHOSPHAMIDE (Drug)
结局指标
主要结局
progression-free survival (PFS)
时间窗: up to 4 years
PFS is defined as the time from randomization to first documentation of objective disease progression or death due to any cause, whichever occurs first.PFS will be censored on the date of the last evaluable on study tumor assessment documenting absence of progressive disease for patients who are alive,on study and progression free at the time of the analysis.Alive patients having no tumor assessments after baseline will have time to event endpoint censored on the date of randomization.Disease status will be evaluated according to RECIST 1.1 criteria.
次要结局
- Best overall response rate (ORR)(up to 4 years)
- Duration of response(up to 4 years)
- Resection rate(up to 4 years)
- Time to strategy failure (TSF)(up to 4 years)
- Time to 2nd progressive disease(up to 4 years)
- Overall toxicity rate(up to 4 years)
- Overall survival (OS)(up to 4 years)
- Toxicity rate(up to 4 years)
研究者
Alfredo Falcone
Prof.
Azienda Ospedaliero, Universitaria Pisana