Liposomal iRInotecan, Carboplatin or oXaliplatin for Esophagogastric Cancer

Inclusion Criteria: * Patients must provide written informed consent according to International Conference on Harmonization (ICH)/Guideline for Good Clinical practice (GCP), and national/local regulations prior to any screening procedures. * Male or female adult patients (\> 18 years). * Patients with histologically confirmed diagnosis of metastatic or irresectable human epidermal growth (HER2) negative adenocarcinoma of the stomach or oesophagus; patients with HER2 positive disease are eligible when treatment with trastuzumab is contraindicated. If histology cannot be obtained, cytology is acceptable to prove metastatic disease. * Patients with metastatic or irresectable adenocarcinoma of the stomach or oesophagus not pre-treated with chemotherapy or radiotherapy for irresectable or metastatic disease. Palliative radiotherapy on the primary tumor or a metastatic lesion is allowed if other untreated lesions eligible for evaluation are present. * Measurable disease as assessed by RECIST 1.1 * Eastern Cooperative Oncology Group (ECOG) (WHO) performance status 0-2 * Patient has adequate bone marrow and organ function as defined by the following laboratory values: * Absolute Neutrophil Count (ANC) \> 1.5 x 109 /L * Hemoglobin (Hgb) \> 5.6 mmol/L * Platelets \> 100 x 109 /L * Serum total bilirubin within ≤ 1.5 x ULN (upper limit of normal); or total bilirubin \< 3.0 x upper limit of normal (ULN) with direct bilirubin within normal range in patients with well documented Gilbert's syndrome; biliary drainage is allowed for biliary obstruction * Serum creatinine \< 1.5 x ULN or creatinine clearance \>30 mL/min/1.73 m2 * Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) \< 2.5x ULN within normal range or \< 5.0 x ULN if liver metastases are present * If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test, beta-human chorionic gonadotropin (β-hCG) documented 72 hours prior to the first administration of study drug. If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator during the period of administration of study drug and after the end of treatment as recommended. * Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. Exclusion Criteria: * Prior systemic treatment for metastatic or irresectable stomach or oesophageal cancer. * Evidence of disease progression within six months after completion of adjuvant or neoadjuvant treatment (whichever is last) containing a fluoropyrimidine and/or platinum compound and/or irinotecan; progression on neoadjuvant chemoradiation with carboplatin area under the curve (AUC2) and paclitaxel 50 mg/m2 within this time frame is allowed. * All target lesions in a radiation field without documented disease progression. 11 * Patient has known brain metastases, unless previously treated and well-controlled for at least 3 months (defined as clinically stable, no edema, no steroids and stable in 2 scans at least 4 weeks apart). * Past or current malignancy other than entry diagnosis interfering with prognosis of metastatic esophagogastric cancer. * Known uncontrollable hypersensitivity or contraindications to any of the components of liposomal irinotecan (Nal-IRI) other liposomal irinotecan formulations, irinotecan, fluoropyrimidines, leucovorin, oxaliplatin, carboplatin. Patients with previous dose reductions or delays are eligible. * Complete dihydropyrimidine dehydrogenase deficiency . * Patient has active, uncontrolled bacterial, viral or fungal infection(s) requiring systemic therapy. * Patient has known past or active infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C. * Signs of interstitial lung disease (ILD) * Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate patient participation in the clinical study. * Use of other investigational drugs within 30 days of enrollment. * Patient is enrolled in any other clinical protocol or investigational trial that will interfere with the primary endpoint. * Patients who in the investigators' opinion may be unwilling, unable or unlikely to comply with requirements of the study protocol. * Current use or any use in last two weeks of strong cytochrome P4503A (CYP3A-enzyme), CYP2C8, and/or strong UDP glucuronosyltransferase (UGT1A) inhibitors/inhibitors * Breast feeding, known pregnancy, positive serum pregnancy test or unwillingness to use a reliable method of birth control, during therapy and for 3 months following the last dose of study treatment. * Treatment within 4 weeks with dihydropyrimidine dehydrogenase (DPD) inhibitors, including sorivudine or its chemically related analogues such as brivudine. * Pre-existing motor or sensory neurotoxicity greater than WHO grade 1.