Pre- and Postoperative Chemotherapy Including Bevacizumab in Potentially Curable Metastatic Colorectal Cancer (mCRC). A Multicenter, Single Arm Phase I/II Academic Trial
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- The primary objective of this study is the Resectability (R0) rate after neoadjuvant Bevacizumab in potentially resectable mCRC.
研究概览
简要总结
Major attempt is being given to the potential of curing patients with metastatic colorectal cancer due to the recognition of dramatic change in survival figures achieved in palliative chemotherapy combination treatment protocols. Achieving resectablity rates in previously unresectable patients has been defined as study endpoint among other well known primary and secondary objectives. Curing metastatic colorectal cancer is most likely in resectable patients and therefore the logical next step after completion of chemotherapy combination studies (e.g. EORTC 40983) is the addition of targeted agents. Bevacizumab has the most valid data of improving outcome figures and was therefore chosen as additional agent. Safety of the combination with Xelox was demonstrated in the investigators pilot trial (Gruenberger JCO 2006, ASCO 2006, WCGC 2006, ESMO 2006), consequently response rate and resection rate will be the primary endpoints in this trial.
STUDY OBJECTIVES
Primary Objective The primary objective of this study is the Resectability (R0) rate after neoadjuvant Bevacizumab in potentially resectable mCRC.
Secondary Objectives The secondary objectives of this study include
- Feasibility with regards to GI bleeding and wound healing complications after surgery of liver metastases
- General safety
- Overall Response Rate (ORR)
- Recurrence Free Survival (RFS)
- Overall Survival (OS)
STUDY DURATION Recruitment is planned for 12 months. Patients will be treated for 6 cycles XELOX and 5 cycles Bevacizumab. Surgery will be performed 2 weeks after the last Capecitabine administration, allowing a time window of 5 weeks between the last Bevacizumab administration and surgery.
Therapy with 6 cycles of XELOX and Bevacizumab will be restarted 4-5 weeks after surgery.
With a Follow up period of 2 years after the last enrolled patient, in order to assess RFS and OS, the trial will last for approx. 3 years.
NUMBER OF CENTRES Four centres with a high level of experience in the surgery of liver metastases are planned to participate in this study.
SELECTION CRITERIA
Total Number of Patients and Target Population The planned total sample size for this study is 43 patients. Patients with potentially resectable metastatic colorectal cancer previously untreated for metastatic disease will be enrolled in this trial.
详细描述
Major attempt is being given to the potential of curing patients with metastatic colorectal cancer due to the recognition of dramatic change in survival figures achieved in palliative chemotherapy combination treatment protocols. Achieving resectablity rates in previously unresectable patients has been defined as study endpoint among other well known primary and secondary objectives. Curing metastatic colorectal cancer is most likely in resectable patients and therefore the logical next step after completion of chemotherapy combination studies (e.g. EORTC 40983) is the addition of targeted agents. Bevacizumab has the most valid data of improving outcome figures and was therefore chosen as additional agent. Safety of the combination with Xelox was demonstrated in our pilot trial (Gruenberger JCO 2006, ASCO 2006, WCGC 2006, ESMO 2006), consequently response rate and resection rate will be the primary endpoints in this trial.
STUDY OBJECTIVES
Primary Objective The primary objective of this study is the Resectability (R0) rate after neoadjuvant Bevacizumab in potentially resectable mCRC.
Secondary Objectives The secondary objectives of this study include
- Feasibility with regards to GI bleeding and wound healing complications after surgery of liver metastases
- General safety
- Overall Response Rate (ORR)
- Recurrence Free Survival (RFS)
- Overall Survival (OS)
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histologically confirmed diagnosis of metastatic CRC including potentially resectable liver metastases, untreated yet with chemotherapy for metastatic disease
- •At least one measurable metastatic lesion (as per RECIST criteria)
- •Prior adjuvant or neo-adjuvant chemotherapy/radiotherapy allowed
- •ECOG performance status 0 or 1
- •Signed written informed consent
- •life expectancy greater than 3 months
- •patients below 18 years of age
- •Adequate haematological function: White blood count ≥ 3 x 1000/L with neutrophils ≥ 1.5 x 1000/L, platelet count ≥ 100 x 1000/L, and hemoglobin ≥ 5.6 mmol/L (9g/dL)
- •Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) range, alkaline phosphatase, Aspartate aminotransferase (ASAT) and Alanin aminotransferase (ALAT) ≤ 5 x ULN
- •Serum creatinine ≤ 1.25 ULN and/or creatinine clearance ≥ 60 ml/min
- •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
- •INR ≤ 1.5 and PTT ≤ 1.5 x ULN within 7 days prior to enrolment
- •Women of childbearing potential must have a negative serum pregnancy test done 1 week prior to the administration of the study drug. She and her partner should prevent pregnancy (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) up to at least 6 months after last treatment completion or the last drug dose, whatever happens first.
- •Patient must be able to comply with the protocol
- •Exclusion Criteria
- •Extrahepatic disease, except concurrent diagnosis of primary CRC
- •Prior chemotherapeutic treatment for metastatic CRC
- •Serious, non healing wound, ulcer, or bone fracture.
- •Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment,
- •Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications
- •Lack of physical integrity of the upper gastro-intestinal tract, malabsorption syndrome, or inability to take oral medication
- •Pregnancy (absence to be confirmed by ß-HCG test) or lactation
- •Men of childbearing potential not willing to use effective means of contraception
- •Previous exposure to anti-VEGF antibodies
- •Treatment with any investigational agent(s) within 4 weeks prior to study entry
- •Known allergic/hypersensitivity reaction to any of the components of study treatments
- •Clinically significant cardiovascular disease, for example CVA (6 months before treatment start), myocardial infarction (6 months before treatment start), unstable angina, NYHA grade 2 CHF, or uncontrolled hypertension.
- •History of significant neurologic or psychiatric disorders including dementia, seizures, bipolar disorder
- •Medical or psychological condition that would not permit the patient to complete the study or sign informed consent
- •Known alcohol or drug abuse
- •Clinical or radiological evidence of CNS metastases.
- •Past or current history (within the last 2 years prior to treatment start) of other malignancies except metastatic colorectal cancer (Patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible).
- •History of thromboembolic or haemorrhagic events within 6 months prior to treatment.
- •Evidence of bleeding diathesis or coagulopathy
- •Current or recent (within 10 days prior to study treatment start) ongoing treatment with anticoagulants for therapeutic purposes i.e. except for anticoagulation for maintenance of patency of permanent indwelling IV catheters.
- •Chronic daily treatment with aspirin (> 325 mg/day) or clopidogrel (>75 mg/day).
- •Chronic daily treatment with corticosteroids (dose of 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids).
- •Any other serious or uncontrolled illness which, in the opinion of the investigator, makes it undesirable for the patient to enter the trial
- •gastrointestinal ulceration
- •Known peripheral neuropathy NCI CTC Grade
- •Absence of deep tendon reflexes (DTRs) as the sole neurological abnormality does not render the patient ineligible
排除标准
- 未提供
研究组 & 干预措施
Xelox, Bev
干预措施: Bevacizumab (Drug)
结局指标
主要结局
The primary objective of this study is the Resectability (R0) rate after neoadjuvant Bevacizumab in potentially resectable mCRC.
时间窗: 4 months
次要结局
- Feasibility with regards to GI bleeding and wound healing complications after surgery of liver metastases(1 month)
- Overall Response Rate (ORR)(4 months)
- Recurrence Free Survival (RFS)(3 years)
- Overall Survival (OS)(5 years)
研究者
Univ.Prof.MD Thomas Grünberger
Prof
Austrian Society Of Surgical Oncology