Gastroesophageal cancer
Conditions
Sponsors
Academic Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female adult patients (> 18 years) - Primaire tumor or metastasis accessible for repeat fresh histological biopsies - dMMR identified by IHC of mismatch repair proteins MLH1, PMS2, MSH2, and MSH6 - Patients with histologically confirmed diagnosis of metastatic or irresectable HER2 negative adenocarcinoma of the stomach or oesophagus; patients with HER2 positive disease are eligble 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 eligble for evaluation are present - Measurable disease as assessed by RECIST 1.1 - ECOG (WHO) performace status 0-2 - Patient has adequate hepatic, renal and hematological function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Past or current malginancy other than entry diagnosis interfering with prognosis of metastatic esophagogastric cancer
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effects of the combination of two chemotherapies followed by immunostimulants on the interferon gamma expression and infiltration of cytotoxic T cells in the tumour microenvironment;Secondary Objective: Secondary objectives - Overall survival and compare with a propensity score matched cohort from the Dutch randomized phase 2 LyRICX study and Dutch Cancer Registry - Progression free survival and compare with a propensity score matched cohort - Response rate according to RECIST 1.1 - Adverse events according to NCI CTCAE 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 Exploratory endpoints: 1 Explore the impact of cytotoxic therapy on the tumor immune microenvironment 2 Identify candidate markers of response to PD-1 pathway inhibitors and potential aetiologies of de novo or acquired resistance 3 Explore whether 1 and 2 are related to response to treatment and survival 4 Patient derived tumor organoids and autologous immune cell co-culturing to asses markers of response to treatment and identify resistance pathways;Primary end point(s): Interferon gamma expression and number of infiltrating cytotoxic T cells;Timepoint(s) of evaluation of this end point: Fresh tumor biopsies, faeces and blood in week 0, week 6, week 14. Extra blood sample in week 7. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - overall survival - progression free survival - response rate according to RECIST 1.1 - Adverse events according to NCI CTCAE version 5.0 - Quality of life - Percentage of patients proceeding to subsequent lines of treatment after progression and describe the types of subsequent treatments - Reasons for forgoing subsequent treatment after progression ;Timepoint(s) of evaluation of this end point: - CT scan in week 0, week 6, week 14, and every 12th week until progression - Laboratory assessment at start of each cycle - questionnaire neurotoxicity every 3 weeks, up until week 9 - questionnaire quality of life every 12 weeks | — |
Countries
Netherlands
Contacts
Public ContactStudy Coordinator
Academic Medical Center
Outcome results
None listed