greccar 8: primary tumor resection in rectal cancer with unresectable metastasis

Conditions: Rectal Adenocarcinoma

Summary: a prospective, open, multicenter, randomized iii trial with two arms: * arm a: primary tumor resection , followed by chemotherapy * arm b: chemotherapy alone. compare overall 2-year survival rates in patients treated for resectable rectal adenocarcinoma with unresectable metastasis, treated either with the primary tumor resection with chemotherapy +/- target therapy, or with chemotherapy (+/- target therapy) alone.


Eligibility criteria:
inclusion criteria: * non-complicated primary tumor (i.e. tumor without obstruction, bleeding, abscess or perforation requiring emergency surgery and/or contra-indicating first-line chemotherapy) * unresectable synchronous metastases * ecog performance status 0-1 * rectal adenocarcinoma (\<15 cm from the anal verge) with few or no symptoms and unresectable metastasis (assessed by the investigator) unsuitable for curative treatment * no known unresectable primary tumor (with clear margin \>1mm) on ct-scan and mri * no disease progression under chemotherapy (for at least 4 cycles); * assessment of kras status before randomization (wild type or mutated); * life expectancy without cancer \>2 years * white blood cell count ≥ 3 x 109/l, with neutrophils ≥ 1,5 x 109/l, platelet count ≥ 100 x 109/l, hemoglobin°≥ 9 g/dl (5,6 mmol/l) * total bilirubin ≤ 1.5 x uln (upper limit of normal), asat and alat ≤ 2.5 x uln, alkaline phosphatase°≤°1.5°x uln, serum creatinine ≤ 1.5 x uln; * age ≥ 18 years ≤ 75 years * patients with childbearing potential should use effective contraception during the study and up 6 months after the end of chemotherapy * covered by a health system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research; * signed written informed consent obtained prior to any study-specific screening procedures exclusion criteria: * rectal tumor operated before inclusion * symptoms related to the rectal tumor requiring first intention rectal surgery (appreciated by investigator) * contra-indication for surgery * resectable metastases * complicated (obstruction, bleeding, abscess, perforation) primary tumor requiring emergency surgery and/or contra-indicating first line-chemotherapy * non-resectable primary tumor (with wild margin) * age \> 75 years \< 18 years * ecog performance status \> 2 * under nutrition (albumin \< 30 g/l) * peritoneal carcinomatosis * disease progression under chemotherapy (recist 1.1 criteria) * known hypersensitivity reaction or specific contraindications to any of the components of study treatments * clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months, or high risk of uncontrolled arrhythmia * pregnancy (absence to be confirmed by ß-hcg test) or breast-feeding; * previous malignancy in the last 5 years * medical, geographical, sociological, psychological or legal conditions that would prevent the patient from completing the study or signing the informed consent; in the investigator's opinion * any significant disease which, in the investigator's opinion, excludes the patient from the study * under an administrative or legal supervision.

Keywords: rectal adenocarcinoma unresectable surgery chemotherapy