The CRITICS-II trial aims to identify the optimal preoperative regimen in resectable gastric cancer by comparing three investigational treatment arms: chemotherapy vs. chemotherapy and subsequent chemoradiotherapy vs. chemoradiotherapy. The rationale behind this trial design is based on the following concepts:

• Preoperative treatment is associated with better patient compliance than postoperative regimens
• Preoperative treatment increases the likelihood of disease downsizing/downstaging and radical R0 resections
• Preoperative paclitaxel/carboplatin-based concurrent chemoradiotherapy and DOC chemotherapy are effective, feasible and safe regimens

Inclusion Criteria:

• TNM 8th ed stage IB-IIIC gastric cancer (histologically proven); tumour bulk has to be in the stomach but may involve gastro-oesophageal junction
• WHO < 2
• Age ≥ 18 yrs
• Resectable adenocarcinoma of the stomach or gastro-oesophageal junction
• No prior abdominal radiotherapy
• Haematology: Hb ≥5.0 mmol/l; leukocytes≥3.0x109/l, neutrophils ≥1.5x109/l, thrombocytes ≥100x109/l
• Renal function: serum creatinine ≤1.25x ULN, creatinine clearance ≥ 50 ml/min (calculated by Cockcroft and Gault formula) Liver function: total bilirubin ≤1.5x ULN, alkaline phosphatase and ASAT/ALAT ≤ 3x ULN
• At staging laparoscopy (mandatory) obtained biopsies of suspected peritoneal lesions and/or substantial free peritoneal fluid if any should be pathologically proven tumor negative
• Written informed consent
• Expected adequacy of follow-up
• Caloric intake≥1500 kcal/day, verified by a dietician before registration.
• if caloric intake is < 1500 kcal/day or if bodyweight has decreased > 10% over the last 6 months or > 5% over the last month, dietary intervention such as oral nutritional support or enteral tube feeding is mandatory

Exclusion Criteria:

• T1N0 disease (assessed by endoscopic ultrasound)
• Distant metastases
• Inoperable patients; due to technical surgery-related factors or general condition
• Previous malignancy, except adequately treated non-melanoma skin cancer or in-situ cancer of the cervix uteri; in case of a previous other malignancy with a disease-free period≥5 years, inclusion can be accepted after consultation of the principal investigator
• Solitary functioning kidney that will be within the radiation field
• Major surgery within 4 weeks prior to study treatment start, or lack of complete recovery from the effects of major surgery
• Uncontrolled (bacterial) infections
• Significant concomitant diseases preventing the safe administration of study drugs or likely to interfere with study assessments
• Uncontrolled angina pectoris, cardiac failure or clinically significant arrhythmias
• Continuous use of immunosuppressive agents equivalent to >10 mg daily prednison
• Concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine
• Neurotoxicity > CTC grade 1
• Pregnancy or breast feeding
• Patients (M/F) with reproductive potential not implementing adequate contraceptive measures
• Gastric or gastro-esophageal stent within radiation field