cancer of esophagus and stomach Metastatic upper gastrointestinal cancer
Conditions
Interventions
1. Nal-IRI 70 mg/m² (water free base), folinic acid 400 mg/m², fluorouracil
2400 mg/m² over 46 h, every 2 weeks.
2. Capecitabine 1000 mg/m2 and carboplatin AUC5 with/without Nivolumab, every
three
Sponsors
Amsterdam UMC
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * 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. * 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 for RECIST evaluation are present. Chemoradiation with carboplatin area under the curve (AUC) 2 and paclitaxel 50 mg/m2 for irresectable disease is allowed if subsequent disease progression is proven on radiological imaging. * Measurable/evaluable disease as assessed by RECIST 1.1 * ECOG (WHO) performance status 0-2 * Adequate hepatic, renal and hematological function
Exclusion criteria
Exclusion criteria: * Serum total bilirubin >=1.5 x ULN (biliary drainage is allowed for biliary obstruction) * Severe renal impairment (CLcr grade 2 * Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) in last 6 months * NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure. Or known abnormal ECG with clinically significant abnormal findings * Current use or any use in last two weeks of strong CYP3A-enzyme, CYP2C8, and/or strong UGT1A inhibitors/inducers * Known complete dihydropyrimidine dehydrogenase (DPD) deficiency * Treatment within 4 weeks with DPD inhibitors, including sorivudine or its chemically related analogues such as brivudine * Pre-existing motor or sensory neurotoxicity greater than CTCAE grade 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival (PFS1) and neurotoxicity | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints * Overall survival * Response rate according to RECIST 1.1 * Adverse events according to NCI CTC version 5.0 * Quality of life * Percentage of patients proceeding to subsequent lines of treatment after progression and describe the types of treatment * Reasons for forgoing subsequent treatment after progression - To compare the primary objective and above mentioned secondary objectives for patients treated with and without nivolumab - To compare the progression free survival 2: time from reintroduction carboplatin, oxaliplatin or Nal-IRI after first moment of disease progression, untill disease progression. Exploratory endpoints • Relative abundance of stroma and tumor immune infiltrate in metastatic tumor tissue as predictor of response to treatment and survival. • Stromal markers, including ADAM12 in metastatic tumor tissue and blood as predictor of response to treatment and survival. • Patient derived tumor organoids to assess markers of response to treatment and identify resistance pathways. • Baseline ctDNA levels and changes in ctDNA as a marker of response to treatment. • Baseline characteristics of and changes in the fecal microbiome as a biomarker for response to treatment and toxicity. • Cost effectiveness. | — |
Countries
Netherlands
Outcome results
None listed