Capecitabine for Gastric adenocarcinoma|Gastroesophageal junction adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Signed informed consent"}
• {"criterion_text":"- Patients must be willing to undergo esophagogastroscopy and biopsies prior to start of treatment and during treatment at defined timepoints"}
• {"criterion_text":"- Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 14 days prior to the start of treatment"}
• {"criterion_text":"- Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. Men receiving atezolizumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 31 weeks after the last dose of investigational product. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men do not require contraception)"}
• {"criterion_text":"- For women of childbearing potential*: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the last dose of atezolizumab after the last dose of atezolizumab (bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices)"}
• {"criterion_text":"- Primary resectable, histologically confirmed gastric or gastro-esophageal junction adenocarcinoma"}
• {"criterion_text":"- ECOG performance status of 0 or 1"}
• {"criterion_text":"- Patients age 18 and older"}
• {"criterion_text":"- No signs of distant metastases"}
• {"criterion_text":"- Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment: o ANC ≥ 1.5 × 109 /L (1500/µL) without granulocyte colony-stimulating factor support o Lymphocyte count ≥ 0.5 × 109 /L (500/µL) o Platelet count ≥ 100 × 109 /L (100,000/µL) without transfusion o Hemoglobin ≥ 5,6mmol/L (patients may be transfused to meet this criterion) o AST, ALT, and alkaline phosphatase (ALP) ≤ 2.5 × upper limit of normal (ULN) o Serum bilirubin ≤ 1.5 × ULN except for patients with known Gilbert disease: serum bilirubin level ≤ 3 × ULN o Serum creatinine ≤ 1.5 × ULN or Creatinine clearance ≥ 40 mL/min (calculated using the Cockcroft-Gault formula) o Serum albumin ≥ 25 g/L o For patients not receiving therapeutic anticoagulation: INR or aPTT ≤ 1.5 × ULN"}
• {"criterion_text":"- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen"}
• {"criterion_text":"- CT-scan of thorax and abdomen < 4 weeks to registration. PET-scan and EUS are required for GEJ tumors and are optional for gastric cancers"}
• {"criterion_text":"- For diffuse type gastric cancers, diagnostic laparoscopy should be performed and show no signs of peritoneal metastases"}

Exclusion criteria

• {"criterion_text":"- Clinical symptoms or radiological suspicion of perforation"}
• {"criterion_text":"- Signs or suspicion of metastatic disease"}
• {"criterion_text":"- Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis"}
• {"criterion_text":"- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted."}
• {"criterion_text":"- Active tuberculosis"}
• {"criterion_text":"- Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina"}
• {"criterion_text":"- Major surgical procedure other than diagnostic laparoscopy, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure, other than for this diagnosis, during the study"}
• {"criterion_text":"- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia"}
• {"criterion_text":"- Prior allogeneic stem cell or solid organ transplantation"}
• {"criterion_text":"- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications"}
• {"criterion_text":"- Underlying medical conditions that will make the administration of the study drug hazardous or obscure the interpretation of toxicity determination of adverse events"}
• {"criterion_text":"- Positive test for hepatitis B surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection"}
• {"criterion_text":"- History of testing positive human immunodeficiency virus or known acquired immunodeficiency syndrome (AIDS)"}
• {"criterion_text":"- History of uncontrolled medical or psychiatric illness. Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule"}
• {"criterion_text":"- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within months after the last dose of study treatment"}
• {"criterion_text":"- History of malignancy within 3 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer"}
• {"criterion_text":"- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab"}
• {"criterion_text":"- Current treatment with anti-viral therapy for HBV"}
• {"criterion_text":"- Treatment with investigational therapy within 28 days prior to initiation of study treatmen"}
• {"criterion_text":"- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti−CTLA-4, anti−PD-1, and anti−PD-L1 therapeutic antibodies"}
• {"criterion_text":"- Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment"}
• {"criterion_text":"- Conditions requiring systemic treatment with either corticosteroids (>10mg daily prednisone equivalents or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease"}
• {"criterion_text":"- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins"}
• {"criterion_text":"- Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation"}
• {"criterion_text":"- Intercurrent illnesses, including but not limited to infections, that are determined incompatible with the study treatment and protocol by the study team"}

Primary endpoints

• {"endpoint_text":"- Safety, measured by SAEs and treatment related complications leading to delays in systemic treatment and/or surgery","definition_or_measurement_approach":"Measured by SAEs and treatment-related complications leading to delays in systemic treatment and/or surgery"}

Secondary endpoints

• {"endpoint_text":"- Pathological tumor regression grade and the rate of complete and near-complete response, measured using the Mandard tumor regression grading system","definition_or_measurement_approach":"Measured using the Mandard tumor regression grading system"}
• {"endpoint_text":"- Effect of therapy on intratumoral T-cell infiltration, CD4/CD8 ratio and immune checkpoints upregulation in the time interval post-atezolizumab monotherapy, post combination treatment with chemotherapy and at surgery","definition_or_measurement_approach":"Assessment of intratumoral T-cell infiltration, CD4/CD8 ratio and immune checkpoint expression on tissue samples at specified timepoints (post-monotherapy, post-combination, at surgery)"}
• {"endpoint_text":"- Correlation of pre-treatment T-cell infiltration and pathological response","definition_or_measurement_approach":"Correlation analysis between baseline T-cell infiltration measures and pathological response outcomes"}
• {"endpoint_text":"- Radiological tumor regression, and when possible the (immune) recist criteria, will be assessed prior to cycle 4 of combination treatment","definition_or_measurement_approach":"Radiological assessment prior to cycle 4 using tumor regression measures and (immune) RECIST criteria when possible"}
• {"endpoint_text":"- Immunogenic mutational load as determined by tumor tissue DNA WES (with peripheral blood DNA WES as a control for somatic mutation sorting) and correlated to response (only genes relating to gastric cancer and/or immune-related genes, deemed informational for this study, will be assessed)","definition_or_measurement_approach":"Tumor tissue DNA whole-exome sequencing (with peripheral blood DNA WES control); mutational load correlated to response using selected gene panels"}
• {"endpoint_text":"- Immune suppressive pathways and IFN-y induced gene expression will be analyzed by use of RNA sequencing on pre- and post-therapy tissue. Baseline immune gene signatures will be assessed for their predictive value of response to treatment","definition_or_measurement_approach":"RNA sequencing on pre- and post-therapy tissue to analyze immune-suppressive pathways and IFN-γ induced gene expression; baseline immune gene signatures evaluated for predictive value"}
• {"endpoint_text":"- For a limited amount of patients, changes in the tissue and peripheral blood TCR repertoire and clonality will be determined","definition_or_measurement_approach":"TCR repertoire and clonality analysis on tissue and peripheral blood samples for a subset of patients"}
• {"endpoint_text":"- Date of relapse, as determined by disease recurrence or disease-related death during followup after surgery. Follow-up will be performed according to the assessment table","definition_or_measurement_approach":"Date of relapse determined by clinical/radiological recurrence or disease-related death during follow-up per assessment schedule"}
• {"endpoint_text":"- When enough material is available, organoids cultured from both normal and tumor tissue preand post-therapy will be grown and stored","definition_or_measurement_approach":"Culture and storage of organoids from normal and tumor tissue when sufficient material is available (exploratory)"}

Netherlands

Earliest CTIS Part Ii Submission Date

15-10-2024

Latest Decision Or Authorization Date

21-11-2024

Processing Time Days

37

Number Of Sites

2

Number Of Participants

21

Primary sponsor

Full Name

Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands