Open, Randomized, Multicenter, Randomized Phase II Trial Comparing the Combination of Cetuximab With Oxaliplatin/5-FU/FA Versus the Combination of Cetuximab With Irinotecan/5-FU/FA as Neoadjuvant Treatment in Patients With Non-Resectable Colorectal Liver Metastases
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 135
- 试验地点
- 21
- 主要终点
- Tumor response, defined as partial and complete response according to RECIST (Response Evaluation Criteria in Solid Tumors) - criteria in the intention-to-treat [ITT-] population
研究概览
简要总结
General Objectives:
- To test the feasibility of neoadjuvant treatment with cetuximab/chemotherapy followed by liver resection
- To determine the optimal combination (cetuximab/FOLFOX versus cetuximab/FOLFIRI) for further trials in preoperative chemotherapy
详细描述
Patients with liver metastasis will be screened for this study. Eligible patients will complete the pretreatment evaluation including an abdominal CT scan that will be presented to the local surgeon and the radiologist for proving of resectability of hepatic lesions. Additionally, CT scans will be reviewed by three reference surgeons. In case of non-resectability, as defined above, CT- or ultrasound- guided biopsy of one of the liver metastases will be performed, unless biopsy material is available from prior biopsy of one of the liver metastases.
Instead of an ultrasound-guided biopsy, a CT-guided biopsy may be performed.
Formalin-fixed, paraffin embedded metastatic tissue will be sent to reference laboratory (Prof. Störkel, Wuppertal) for immunohistochemical analysis of EGFR- expression.
Additionally tissue will be stored in "RNA later" for gene expression analysis if agreed by the patient.
Additionally, the primary tumor will be collected and sent to the reference laboratory for analysis of EGFR- expression (if agreement of the patient exists).
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
- •Patients with non-resectable, histologically confirmed, synchronous or metachronous colorectal liver metastases. Patients with non-resectable metastases are defined as; patients with five or more liver metastases; and/or patients with liver metastases that are technically non-resectable (local surgeon in cooperation with local radiologist will define non-resectability on the basis of remaining functional liver tissue, infiltration of all liver veins, infiltration of both liver arteries, both portal branches or both bile ducts).
- •Patients with simultaneous liver metastases are eligible, if the primary tumor has been resected at least 1 month prior to chemotherapy.
- •Karnofsky Performance Status ≥ 80
- •Informed consent
- •Adequate bone marrow function, liver and renal function (neutrophils > 1.5 x 10^9/l; thrombocytes > 100 x 10^9/l; hemoglobin > 8.0 g/l; bilirubin ≤ 1.5 x upper limit of normal [ULN] and not increasing more than 25% within the last 4 weeks; ALAT and ASAT < 5 x UNL; serum creatinine ≤ 1.5 x UNL)
- •Age ≥ 18 years
排除标准
- •Any evidence of extrahepatic metastases, lymph node metastases and primary tumor recurrence
- •Prior chemotherapy (except adjuvant chemotherapy with an interval of ≥ 6 months)
- •Previous exposure to EGFR (epidermal growth factor receptor)-targeting therapy
- •Radiotherapy or major abdominal or thoracic surgery (excluding diagnostic biopsy or port implantation) ≤ 4 weeks before study entry
- •Concurrent systemic immune therapy, chemotherapy, or hormone therapy
- •Investigational agents or participation in clinical trials within 30 days before start of the treatment in study
- •Clinically relevant coronary disease or myocardial infarction within 12 months before study entry
- •Peripheral neuropathy > CTC grade I
- •Inflammatory bowel disease
- •Previous malignancy (except colorectal cancer, history of basal cell carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment)
- •History of severe psychiatric illness
- •Drug or alcohol abuse
- •Breast feeding or pregnant women, no effective contraception if risk of conception exists (male and female patients)
研究组 & 干预措施
1
Cetuximab and FOLFIRI
干预措施: Cetuximab (Drug)
1
Cetuximab and FOLFIRI
干预措施: Liver resection (Procedure)
1
Cetuximab and FOLFIRI
干预措施: Cetuximab and FOLFIRI (Drug)
2
Cetuximab and FOLFOX
干预措施: Cetuximab (Drug)
2
Cetuximab and FOLFOX
干预措施: Liver resection (Procedure)
2
Cetuximab and FOLFOX
干预措施: Cetuximab and FOLFOX (Drug)
结局指标
主要结局
Tumor response, defined as partial and complete response according to RECIST (Response Evaluation Criteria in Solid Tumors) - criteria in the intention-to-treat [ITT-] population
次要结局
- Rate of R0 liver resection (ITT- population)
- Progression free survival (ITT- population)
- Disease free survival after resection (ITT- population)
- Overall survival (ITT- population)
- Safety (all patients that received any study drug)
- Molecular predictive markers for response and toxicity