Randomised Phase 2 Study Comparing Pathological Responses Observed on Colorectal Cancer Metastases Resected After Preoperative Treatment Combining Cetuximab With FOLFOX or FOLFIRI in RAS and B-RAF WT Tumors
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 4
- 试验地点
- 7
- 主要终点
- Major Pathological Response Rate
研究概览
简要总结
To analyze the pathological tumor response on resected colorectal cancer metastases after preoperative treatment with cetuximab combined with FOLFOX or FOLFIRI regimen in a prospective cohort (RAS and B-RAF WT tumors) and to correlate this response with patient's outcome.
详细描述
This is a phase II , openlabel, randomized study in patients with confirmed diagnosis of potentially or borderline resectable metastatic colorectal adenocarcinoma (RAS and B-RAF WT tumors ), who have not received prior chemotherapy for their metastatic disease.
The study is designed to compare pathological responses observed after pre-operative chemotherapy cetuximab with FOLFOX or FOLFIRI.
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
- •Female or male patients with at least 18 years at the time the informed consent is signed
- •ECOG performance status 0 or 1
- •Histological or cytological confirmed diagnostic of adenocarcinoma of the colon or rectum, with or without primary tumour in situ. Wild-type RAS and B-RAF tumor status.
- •Patients with potentially resectable metastatic disease at diagnosis and for whom a chemotherapy first in a curative intent is recommended . Resectability could be planed in one or multiple stage if indicated. As commonly admitted, resectability means the surgical clearance (+/- radiofrequency ablation) of all detectable (liver) lesions with tumor-free margins and compatible with an adequate hepatic reserve. Practically, bilateral tumor location, number and location of lesions, and inadequate hepatic reserve remain the main decisional factors.
- •Partial and minor resection of metastatic disease is allowed within 3 months before inclusion if patient has never received chemotherapy for mCRC.
- •Extra hepatic metastatic location is limited to 1 site.
- •Patients may have received adjuvant chemotherapy or (neo-) adjuvant chemo-radiotherapy to the pelvis, provided the last dose of chemotherapy was administered at least 6 months prior to inclusion (12 months for oxaliplatin). Previous radiotherapy to the pelvis is not an exclusion criterion.
- •Adequate haematological, renal and hepatic function as follows:
- •Haematological:
- •haemoglobin >9g/dl Neutrophils > 1.5 x 109/L Platelets > 100 x 109/L
- •Creatinine< 1.5 x ULN (Upper Limit of Normal)
- •Bilirubin < or equal 1.5 X ULN AST (Aspartate Aminotransferase),and ALT (Alanine Aminotransferase)< or equal 5 x ULN, Phos Alc< or equal 5 x ULN
- •Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active using an acceptable method of contraception.
- •Male patients must be surgically sterile or if sexually active and having a pre-menopausal partner must be using an acceptable method of contraception.
- •Life expectancy of at least 3 months without any active treatment.
排除标准
- •1.Definitively non resectable mCRC at diagnosis
- •2.Prior chemotherapy or systemic therapy for mCRC. Adjuvant chemotherapy for colorectal cancer is not an exclusion criterion provided that it was completed more than 6 months prior to inclusion. Oxaliplatin-based chemotherapy must be completed more than 1 year prior to inclusion.
- •3.Prior utilization of cetuximab, panitumumab (or other anti-EGFR (epidermal growth factor receptor)therapy).
- •4.Previous radiotherapy delivered to the upper abdomen.
- •5 Non mesurable disease( RECIST 1.1 criteria)
- •6.Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiologic assessment.
- •7.Prior major liver resection: remnant liver < 50% of the initial liver volume.
- •8.Non-malignant disease that would render the patient unsuitable for treatment according to this protocol.
- •9.Concurrent central nervous systems metastases
- •10.Peripheric neuropathy ≥ grade
- •11.Interstitial lung disease
- •12.Pregnant or breast feeding.
- •13.The patient has previous or concomitant malignancies, except: Invasive malignancies in remission for more than 5 years and non melanoma skin cancer or carcinoma in situ of the cervix.
研究组 & 干预措施
Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximab
Irinotecan+ + leucovorinL +5-Fluorouracile + cetuximab +'Metastases Resection ( multiple steep surgery possible)
干预措施: Metastases Resection ( multiple steep surgery possible) (Procedure)
oxaliplatin +leucovorin L+5FU+ cetuximab
oxaliplatin +leucovorinL+5-Fluorouracile +cetuximab+'Metastases Resection ( multiple steep surgery possible)
干预措施: Metastases Resection ( multiple steep surgery possible) (Procedure)
oxaliplatin +leucovorin L+5FU+ cetuximab
oxaliplatin +leucovorinL+5-Fluorouracile +cetuximab+'Metastases Resection ( multiple steep surgery possible)
干预措施: 5-Fluorouracile (Drug)
oxaliplatin +leucovorin L+5FU+ cetuximab
oxaliplatin +leucovorinL+5-Fluorouracile +cetuximab+'Metastases Resection ( multiple steep surgery possible)
干预措施: leucovorin L (Drug)
oxaliplatin +leucovorin L+5FU+ cetuximab
oxaliplatin +leucovorinL+5-Fluorouracile +cetuximab+'Metastases Resection ( multiple steep surgery possible)
干预措施: Oxaliplatin (Drug)
oxaliplatin +leucovorin L+5FU+ cetuximab
oxaliplatin +leucovorinL+5-Fluorouracile +cetuximab+'Metastases Resection ( multiple steep surgery possible)
干预措施: Cetuximab (Drug)
Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximab
Irinotecan+ + leucovorinL +5-Fluorouracile + cetuximab +'Metastases Resection ( multiple steep surgery possible)
干预措施: 5-Fluorouracile (Drug)
Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximab
Irinotecan+ + leucovorinL +5-Fluorouracile + cetuximab +'Metastases Resection ( multiple steep surgery possible)
干预措施: leucovorin L (Drug)
Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximab
Irinotecan+ + leucovorinL +5-Fluorouracile + cetuximab +'Metastases Resection ( multiple steep surgery possible)
干预措施: Irinotecan (Drug)
Irinotecan+ + leucovorinL +5-Fluorouracil +cetuximab
Irinotecan+ + leucovorinL +5-Fluorouracile + cetuximab +'Metastases Resection ( multiple steep surgery possible)
干预措施: Cetuximab (Drug)
结局指标
主要结局
Major Pathological Response Rate
时间窗: Average 3 months (after resection of metastases)
Major pathological response rate (MPRR) is defined as the proportion of patients presenting a major pathological response. Pathologic response will be evaluated according the Rubbia-Brandt Tumor Regression Grade classification .For patients with multiple colorectal metastases the global pathological response will be categorized based on the mean TRG of all metastases.: a major response is defined as a mean TRG \< 3, a partial response is defined for patient presenting a mean TRG ≥3 and \<4, and a no response for patient with a mean TRG ≥4.
次要结局
- Curative resection rate(At time of surgery)
- Metabolic response rate(At time of surgery - average 3 months)
- progression free survival(at 6 months and at 12 months after randomization)
- Overall survival(At the end of the study)
- Clinical response rate(at time of surgery -)
- post operative complications(one month after surgery)
- Chemotherapy-associated hepatotoxicity:(at time of surgery)