stomach cancer
Conditions
Interventions
All patients will be treated with a single cycle of atezolizumab monotherapy,
followed by four cycles of capecitabine, oxaliplatin, docetaxel and
atezolizumab. All treatment cycles will be given pre
Sponsors
Nederlands Kanker Instituut
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Primary resectable, gastro-oesophageal junction adenocarcinoma or gastric adenocarcinoma - WHO performance status of 0 or 1 - No distant metastases - CT-scan
Exclusion criteria
Exclusion criteria: - Clinical symptoms or radiological suspicion of perforation - Active auto-immune disease or documented history of autoimmune disease, or other medical conditions requiring systemic steroid or immunosuppressive medications, except for subjects with vitiligo, diabetes mellitus type 1, residual hypothyroidism due to autommune condition only requiring hormone replacement, psoriasis or resolved childhood asthma/atopy not requiring systemic treatment - 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; - Previous treatment with immune checkpoint inhibitors - History of allergy to study drug components, hypersensitivity reaction to any monoclonal antibody - Positive test for hepatitis B surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection; - History of testing positive human immunodeficiency virus or known acquired immunodeficiency syndrome (AIDS) - Malignancies other than disease under study within 3 years prior to inclusion, requiring systemic treatment or judged by the investigators to be incompatible with the study, except for non-melanoma skin cancer.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety will be measured by SAEs and treatment related complications leading to delays in systemic treatment and/or surgery. Pre-operative treatment-related complications include all immune-related adverse events, attributable to the study medication, that lead to delays in systemic treatment or surgery. Logistical reasons or non-study-medication related complications (i.e. bacterial infections) leading to delays will not be considered dose-limiting toxicity. Post-operative complications, including, but not limited to anastomotic dehiscence/leakage, wound dehiscence, abcess, perforation, bleeding and infection will be recorded. Clinical and/or radiological anastomotic leakage rate of > 10% after (sub)total gastrectomy and > 40% after esophagectomy with cervical anastomosis would be reason to consider the study treatment as unsafe. Feasibility will be measured by adherence to the timelines of the study protocol. All patients will be discussed in our multidisciplinary team meeting prior to start of treatment, at the time of evaluation and prior to the operation. In case of immune related complications, patients will be discussed in our immunotherapy team meeting. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Pathological tumor regression grade and the rate of complete response - 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 - Radiological tumor regression, and when possible the immune recist criteria, will be assessed prior to cycle 4 of combination treatment - Immunogenic mutational load will be determined by tumor tissue DNA WES. Peripheral blood DNA WES will also be performed and used as a control for somatic mutation sorting (only genes relating to gastric cancer and/or immune-related genes, deemed informational for this study, will be assessed ) - Immune suppressive pathways and IFN-y induced gene expression will be analyzed by use of RNA sequencing on pre- and post-therapy tissue; - Date of relapse, as determined by disease recurrence or disease-related death during follow-up after surgery. Follow-up will be performed according to the assessment table. - Organoids | — |
Countries
Netherlands
Outcome results
None listed