Multicentric Randomised Trial for Resectable Gastric Cancer

• Docetaxel (Drug), also known as Taxotere: 3 weekly course of docetaxel i.v in arm 1 and 2
• Oxaliplatin (Drug), also known as Eloxatin: 3 weekly course oxaliplatin as a 2 hr i.v. in arm 1 and 2
• Capecitabine (Drug), also known as Xeloda: oral capecitabine in arm 1 and 2
• gastrectomy (Procedure): resection of gastric cancer after pre-operative chemotherapy for all arms
• radiotherapy of gastric cancer (Radiation): 5 weeks of radiation, 5 times a week with a total of 45 Gy (in arm 2 and 3)
• Paclitaxel (Drug): 5 weeks of paclitaxel i.v once a week (in arm 2 and 3)
• Carboplatin (Drug): 5 weeks of carboplatin i.v once a week (in arm 2 and 3)

Primary outcomes

• Event-Free survival [1 year]: Event-free survival will be measured by clinical outcome and CT-scan

Secondary outcomes

• Time to Event (events: local recurrence, regional recurrence, local-regional recurrence or progression, distant recurrence, or death from any cause) [1 year]: Interval between randomization and event measured by clinical outcome and CT scan
• Time to recurrence (events: local recurrence, regional recurrence, local-regional recurrence or progression, distant recurrence) [1 year]: Interval between randomization and recurrence determined by clinical outcome and CT scan
• Toxicity [1 year]: Number of patients with treatment-related adverse events as assessed by CTCAE v4.0

Sex: All, ages: 18 Years to any

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

• Results publication: Klute KA, Shah MA. Evolving Therapeutics for Resectable Esophageal Adenocarcinoma. J Natl Compr Canc Netw. 2025 May;23(5):e257044. doi: 10.6004/jnccn.2025.7044. PMID 40340830
• Results publication: Slagter AE, Jansen EPM, van Laarhoven HWM, van Sandick JW, van Grieken NCT, Sikorska K, Cats A, Muller-Timmermans P, Hulshof MCCM, Boot H, Los M, Beerepoot LV, Peters FPJ, Hospers GAP, van Etten B, Hartgrink HH, van Berge Henegouwen MI, Nieuwenhuijzen GAP, van Hillegersberg R, van der Peet DL, Grabsch HI, Verheij M. CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer. BMC Cancer. 2018 Sep 10;18(1):877. doi: 10.1186/s12885-018-4770-2. PMID 30200910

• Marcel Verheij, MD, PhD, Principal investigator, The Netherlands Cancer Institute

NIH grants: 2015