FLUOROURACIL for Esophagogastric adenocarcinoma | Advanced (metastatic or locally advanced) esophagogastric cancer

Inclusion criteria

• {"criterion_text":"- Patients must provide written informed consent according to ICH/GCP, and national/local regulations prior to any screening procedures\n- If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative pregnancy test (urine or serum; beta-human chorionic gonadotropin (β-hCG)) documented 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.\n- 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.\n- Male or female adult patients (≥ 18 years).\n- Patients with histologically confirmed diagnosis of metastatic or irresectable 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.\n- Patients with metastatic or irresectable adenocarcinoma of the stomach or oesophagus not pre-treated with systemic therapy 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.\n- Measurable disease as assessed by RECIST 1.1\n- ECOG (WHO) performance status 0-2\n- Patient has adequate bone marrow and organ function as defined by the following laboratory values: o Absolute Neutrophil Count (ANC) > 1.5 x 109 /L o Hemoglobin (Hgb) > 5.6 mmol/L o Platelets > 100 x 109 /L\n- Serum total bilirubin within ≤ 1.5 x ULN (upper limit of normal); or total bilirubin < 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert’s syndrome; biliary drainage is allowed for biliary obstruction\n- Serum creatinine < 1.5 x ULN or creatinine clearance >30 mL/min/1.73 m2 − Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5x ULN within normal range or < 5.0 x ULN if liver metastases are present"}

Exclusion criteria

• {"criterion_text":"- Any prior anti-cancer chemotherapy, biologic or investigational therapy for metastatic or irresectable stomach or oesophageal cancer\n- 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.\n- Use of other investigational drugs within 30 days of enrollment\n- Patient is enrolled in any other clinical protocol or investigational trial that will interfere with the primary endpoint.\n- Patients who in the investigators’ opinion may be unwilling, unable or unlikely to comply with requirements of the study protocol.\n- Current use or any use in last two weeks of strong CYP3A-enzyme, CYP2C8, and/or strong UGT1A inhibitors/inhibitors\n- 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.\n- Treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine.\n- Pre-existing motor or sensory neurotoxicity greater than CTCAE grade 1.\n- Disease progression within six months after completion of (neo)adjuvant chemotherapy containing a fluoropyrimidine and/or platinum compound and/or irinotecan; progression on neoadjuvant or definitive chemoradiation with carboplatin AUC2 and paclitaxel 50 mg/m2 within this time frame is allowed.\n- − All target lesions in a radiation field without documented disease progression\n- 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).\n- Past or current malignancy other than entry diagnosis interfering with prognosis of metastatic esophagogastric cancer.\n- 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.\n- Complete dihydropyrimidine dehydrogenase deficiency.\n- Patient has active, uncontrolled bacterial, viral or fungal infection(s) requiring systemic therapy.\n- Patient has known past or active infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C."}

Primary endpoints

• {"endpoint_text":"- Progression free survival 1 and neurotoxicity. Progression free survival 1 is defined as the time from start of study treatment, until the first moment of disease progression.","definition_or_measurement_approach":"Progression free survival 1 is defined as the time from start of study treatment, until the first moment of disease progression."}

Secondary endpoints

• {"endpoint_text":"- Progression free survival 2: in case of reintroduction of study treatment after progression, progression free survival 2 is the time until progression occurs after this reintroduction. In case of start of second line treatment after progression, the time from start until discontinuation of second line is taken as progression free survival 2.","definition_or_measurement_approach":"Progression free survival 2 defined as time from reintroduction until progression, or time from start until discontinuation of second-line treatment if second-line started."}
• {"endpoint_text":"- Quality of life","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Response rate according to RECIST 1.1","definition_or_measurement_approach":"Assessed according to RECIST 1.1"}
• {"endpoint_text":"- Adverse events according to NCI CTCAE version 5.0.","definition_or_measurement_approach":"Adverse events graded according to NCI CTCAE version 5.0"}
• {"endpoint_text":"- Percentage of patients proceeding to subsequent lines of treatment after progression and describe the types of subsequent treatments","definition_or_measurement_approach":""}
• {"endpoint_text":"- Reasons for forgoing subsequent treatment after progression","definition_or_measurement_approach":""}
• {"endpoint_text":"- To compare the primary and above mentioned secondary objectives for patients treated with and without nivolumab","definition_or_measurement_approach":""}

Netherlands

Earliest CTIS Part Ii Submission Date

24-10-2024

Latest Decision Or Authorization Date

04-11-2025

Processing Time Days

376

Number Of Sites

32

Number Of Participants

322

Primary sponsor

Full Name

Amsterdam UMC

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands