A randomised multicenter clinical trial for patients with multi-organ, colorectal cancer metastases comparing the combination of chemotherapy and removing as many visible tumors as possible by surgery or other means versus chemotherapy alone

INTERVENTION: All patients will receive 3 cycles of chemotherapy with the XELOX regimen (capecitabine and oxaliplatin; 3‐week cycle) or 4 cycles of FOLFOX regimen (5‐FU and oxaliplatin; 2‐week cycle) with or without bevacizumab. A baseline CT or 18F‐FDG‐PET‐CT will be performed no more than 28 days prior to the first dose of chemotherapeutic treatment. After 3 or 4 cycles of XELOX or FOLFOX respectively, a second CT or 18F‐FDG‐PET‐CT will be made and response rates will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). When required for assessing response rates, an MRI scan will be performed. Patients who show clinical benefit, defined as stable disease or response to therapy, will be randomized in one of the two study arms, arm A and arm B. Patients with progressive disease are not eligible study participation and will be treated according to best clinical practice, including all treatment modalities. A CT or 18F‐FDG‐PET‐CT, laboratory analysis, tumor markers and quality of life and multidimensional fatigue inventory questionnaires will be obtained at baseline, after 3 or 4 cycles of chemotherapy and subsequently every three months will be done. Patients included in study arm A will continue to receive XELOX or FOLFOX therapy with or without bevacizumab until disease progression or unacceptable therapy‐related toxicity. After 6 cycles of XELOX or FOLFOX, capecitabine monotherapy is also allowed. In case of unacceptable toxicity of oxaliplatin, capecitabine monotherapy may be considered before 6 cycles of XELOX or FOLFOX. When patients show progressive disease, they will be treated with second line therapy according to best clinical practice. Palliative local treatment options are accepted for a sin CONDITION: Multi‐organ, colorectal cancer metastases ; Cancer PRIMARY OUTCOME: Overall survival (OS), counting from the date of study inclusion to the date of death of the patient SECONDARY OUTCOME: ; 1. Progression‐free survival measured using the inclusion date and the progression date. Progression measured using RECIST 1.1 scoring system for each CT scan at baseline, randomization (after 3 or 4 cycles of chemotherapy) and every 3 months until progressive disease; 2. Safety and efficacy of additional local treatment measured using scoring of Serious Adverse Events using the CTCAE version 4 and Clavien Dindo scoring systems when a SAE occurred; 3. Quality of life measured using the validated EORTC QLQ CR29 and C30 questionaires at baseline, randomization (after 3 or 4 cycles of chemotherapy) and every 3 months until progressive disease; INCLUSION CRITERIA: 1. Patients with CRC metastases in = 2 different organs and 1.1. >3 extrahepatic metastases or 1.2. >5 hepatic metastases not located to one lobe or 1.3. =1 hepatic metastases and either positive para‐aortal lymph nodes or celiac lymph nodes or adrenal metastases or pleural carcinomatosis or peritoneal carcinomatosis 1.4. The primary tumor is excluded as metastatic site 2. Feasible radical tumor debulking. Incomplete tumor debulking is allowed only if at least 80% of metastases can be treated 3. Age >= 18 years 4. WHO performance status 0 – 1 5. Life expectancy of at least 12 weeks 6. Written informed consent