This is a multi-center, open label, randomized phase II trial for patients with previously untreated metastatic or locally advanced esophagogastric cancer, using a pick the winner design to identify the best combination therapy in terms of progression free survival and neurotoxicity.
Name: Liposomal Irinotecan
Description: Iv liposomal irinotecanType: DrugLiposomal irinotecan, leucovorin and 5FU
Name: Carboplatin
Description: IV CarboplatinType: DrugCarboplatin and capecitabine
Name: Capecitabine
Description: PO CapecitabineType: DrugCarboplatin and capecitabine oxaliplatin and capecitabine
Name: Oxaliplatin
Description: IV OxaliplatinType: Drugoxaliplatin and capecitabine
Name: 5-fluorouracil
Description: IV 5-fluorouracilType: DrugLiposomal irinotecan, leucovorin and 5FU
Name: Leucovorin
Description: IV LeucovorinType: DrugLiposomal irinotecan, leucovorin and 5FU
Description: To compare the progression free survival
Measure: Progression free survival Time: 42 monthsDescription: Number of participants with treatment-related Neurotoxicity according to CTCAE v4.0
Measure: Number of participants with treatment-related Neurotoxicity Time: 42 monthsDescription: To determine the overall survival of F-Nal-IRI, capecitabine/Carboplatin (CapCar) and capecitabine/oxaliplatin (CapOx)
Measure: Overall survival Time: 54 monthsDescription: To determine the response rate of F-Nal-IRI, CapCar and CapOx
Measure: response rate Time: 42 monthsDescription: To determine the adverse events of F-Nal-IRI, CapCar and CapOx according to NCI common toxicity criteria (CTC) version 4
Measure: adverse events Time: 42 monthsDescription: Overall Quality of life ranging from 0-100 with 100 being best Quality of Life
Measure: Quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ C30)) Time: 42 monthsDescription: The percentage of patients proceeding to subsequent lines of treatment after progression and describe the types of treatment.
Measure: percentage subsequent treatment lines Time: 42 monthsDescription: Reasons for forgoing subsequent treatment after progression on first-line treatment
Measure: the reasons for forgoing subsequent treatment Time: 42 monthsDescription: Percentage of stroma and tumor immune infiltrate in metastatic tumor tissue as predictor of response to treatment and survival.
Measure: Tumor micro environment Time: 54 monthsDescription: Concentration of ADAM12 in blood
Measure: Stromal markers in blood Time: 54 monthsDescription: Growth velocity of tumor organoids after treatment measured in days
Measure: Growth velocity of patient derived tumor organoids Time: 54 monthsDescription: Concentration circulating tumour DNA (ctDNA) as a marker of response to treatment
Measure: ctDNA Time: 54 monthsDescription: Composition of the fecal microbiome as a potential biomarker for response to treatment and toxicity
Measure: Fecal microbiome Time: 54 monthsDescription: The cost effectiveness in terms of QUALYs associated with treatment of F-Nal-IRI, CapCar and CapOx
Measure: Costs associated with treatment of F-Nal-IRI, CapCar and CapOx Time: 54 monthsDescription: Expression of ADAM12 in metastatic tumor tissue
Measure: Stromal Markers in tumor Time: 54 monthsAllocation: Randomized
Parallel Assignment
There is one SNP
- 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. --- P4503A ---