The MAX Study: A Randomised Phase II/III Study to Evaluate the Role of Mitomycin C, Avastin and Xeloda in Patients With Untreated Metastatic Colorectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 333
- 试验地点
- 36
- 主要终点
- Phase II: - treatment related toxicity
研究概览
简要总结
Although it is possible to cure bowel cancer when it is detected at an early stage, in many cases it may spread to involve other organs and in these cases is generally incurable. Chemotherapy prolongs survival and improves quality of life in such patients, but standard chemotherapy for this disease has not been defined.
There are several possible chemotherapy treatments for patients with bowel cancer, which has spread to other organs. However, these treatments are only partly effective and only work for a limited period of time. Most treatments are associated with a number of possible side effects which may have a detrimental effect on quality of life. Thus, it is imperative that more effective treatments with the lowest possible risk of side effects are developed.
Previous studies have shown that the addition of a new type of antibody treatment (bevacizumab) to an intensive combination chemotherapy regimen improved survival in patients with advanced bowel cancer and extended the time before tumours began to grow. However, intensive chemotherapy is likely to only be a suitable treatment for a proportion of patients with bowel cancer, because intensive chemotherapy causes a high rate of side effects.
This study compares a gentle chemotherapy treatment (capecitabine chemotherapy tablets given by mouth) with the combination of capecitabine and bevacizumab and the combination of capecitabine, bevacizumab and intravenous mitomycin C.
It is expected that a gentle chemotherapy treatment or a gentle chemotherapy treatment combined with bevacizumab would be an appropriate treatment for both young and fit patients as well as older and less fit patients who would not easily tolerate intensive chemotherapy.
详细描述
Aims - The phase II stage of the study aims to determine the relative toxicity of the combination of capecitabine and bevacizumab and the combination of capecitabine, mitomycin C (MMC) and bevacizumab with that of capecitabine monotherapy and to assess tumour response rate (RECIST criteria) for each arm
For Phase III stage the primary objective is to compare progression-free survival (PFS) on the three arms. Secondary objectives are to determine treatment related toxicity; to determine tumour response rates (RECIST criteria); to determine overall survival for each treatment arm; to compare disease related symptoms and Quality of life and to determine cost effectiveness of bevacizumab containing treatments.
Research Plan Synopsis - Trial Design: Randomised, stratified multicentre phase II/III study. The study will proceed in 2 phases, initially a randomised phase II stage evaluating safety after 60 patients (approx 20 per arm) and 150 patients (approx 50 per arm) have completed at least 6 weeks' treatment. This will continue with a randomised phase III stage evaluating activity, toxicity and quality of life measures.
Treatments: Patients will be randomised to treatment in either one of the three arms: I) Capecitabine as monotherapy ; 2) Capecitabine and bevacizumab; or 3) Capecitabine and bevacizumab and MMC.
Drug administration: Arm 1: Capecitabine 2500mg/m2/d (in 2 divided doses) d1-14 q3weekly. Arm 2: Capecitabine administered as per Arm 1 plus Bevacizumab 7.5 mg/kg q3weekly. Arm 3: Capecitabine and Bevacizumab administered as per Arm 2 plus Mitomycin C 7 mg/m2 q 6weekly (maximum dose 14 mg, maximum 4 treatments).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histological diagnosis of colorectal cancer
- •Metastatic disease that is not resectable
- •Age > 18 years
- •Any patient in whom the investigator considers capecitabine monotherapy appropriate
- •Measurable and/or non-measurable disease as assessed by CT scan
- •ECOG performance status 0, 1 or
- •Patients with PS2 should have serum albumin >30 g/L
- •No prior chemotherapy except for adjuvant chemotherapy given in association with (i) complete resection of primary colon or rectal cancer provided there is no clinical, radiological or biochemical evidence of relapse for at least 6 months after completion of adjuvant treatment and/or (ii) complete resection of limited colorectal metastases to liver and/or lung provided there is no clinical, radiological or biochemical evidence of relapse for at least 6 months after completion of adjuvant treatment
- •Adequate bone marrow function with platelets > 100 X 109/l; neutrophils > 1.5 X 109/l i) Adequate renal function, with calculated creatinine clearance >30 ml/min (Cockcroft and Gault). For patients with creatinine clearance <50 ml/min the starting dose of capecitabine may not be greater than 2000 mg/m2/d (see Section 7.1)
- •Adequate hepatic function with serum total bilirubin < 1.5 X upper limit of normal range
- •Life expectancy of at least 12 weeks
- •No other concurrent uncontrolled medical conditions
- •No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer treated with curative intent >2 years previously without evidence of relapse
- •Women and partners of women of childbearing potential must agree to use adequate contraception
- •Written informed consent
排除标准
- •Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol
- •Patients with a lack of physical integrity of the upper gastrointestinal tract, or known malabsorption syndromes.
- •Uncontrolled hypertension
- •Active bleeding disorders within the last 3 months
- •Patients on full anticoagulation with warfarin. (Patients who require full anticoagulation and who wish to participate in the study should be converted to low molecular weight heparin). (Note: patients receiving full anticoagulation with low molecular weight heparin should have no evidence of tumour invading or abutting major blood vessels on any prior CT scan)
- •Participation in any investigational drug study within the previous 8 weeks
- •Patients with uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris
- •Patients with a history of acute myocardial infarction or cerebrovascular accident within the last 12 months
- •Regular use of aspirin (>325mg/day) or NSAIDs (low dose aspirin (<325 mg/d), or occasional use of NSAIDs is acceptable)
- •CNS metastases
- •Major surgical procedure within the last 28 days
- •Serious non-healing wound, ulcer or bone fracture
- •24 hour urinary protein > 2g/ 24 hours ( performed if urine dipstick > 1+ )
- •Pregnancy or lactation
结局指标
主要结局
Phase II: - treatment related toxicity
Phase III: - progression free survival
次要结局
- Phase II: - treatment response
- Phase III:
- - treatment related toxicity
- - treatment response
- - overall survival
- - symptoms of disease, treatment and quality of life
- - cost of therapy and assessment of gain in quality-adjusted progression free survival