HER2-negative unresectable or advanced recurrent gastric cancer Gastric cancer, HER2 negative, unresectable, advanced recurrence
Conditions
Interventions
S-1 administration along with adjustments based on BBT formula in SOX + NIVO therapy
D000971
S-1 Adjustment Increasing BBT formula
Sponsors
Suzuki Nobumi
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. unresectable advanced or recurrent gastric cancer (including esophagogastric junction cancer) histologically diagnosed as HER2-negative adenocarcinoma (papillary adenocarcinoma, tubular adenocarcinoma, poorly differentiated adenocarcinoma), ring cell carcinoma, mucous carcinoma. 2.No prior chemotherapy for gastric cancer. Patients with recurrent cancer after 180 days from the last day of preoperative or postoperative adjuvant chemotherapy are eligible for enrollment. 3.Patients who are judged to be eligible for combination therapy with SOX and nivolumab by the physician in charge of the patient. 4. the S-1 dose obtained from the BBT formula nomogram (page X) is increased from the starting dose described in the package insert. 5. the patient is at least 18 years of age at the time consent is obtained. 6.the patient who consents to contraception 7. ECOG-Performance Status is 0,1 8. Capable of oral intake 9. Have at least one evaluable lesion on contrast-enhanced CT (chest, abdomen, pelvis: slice thickness less than 7 mm) within 28 days prior to registration. 10. Clinical laboratory tests performed within 14 days prior to enrollment meet the following criteria: Neutrophil count over 1,500 /mm3 Platelet count over 10x104 /mm3 Hemoglobin over 8.0 g/dL AST (GOT) under 100 U/L (under 200 U/L in case of liver metastasis) ALT (GPT) under 100 U/L (under 200 U/L in case of liver metastasis) Total bilirubin under 1.5 mg/dL Creatinine under 1.5 mg/dL 11. Patient has given written consent to participate in the study.
Exclusion criteria
Exclusion criteria: 1) Her2-positive gastric cancer (IHC: 3plus or IHC: 2plus with positive ISH) 2) Receiving enteral or intravenous nutritional support or requiring continuous infusion therapy 3) Patient has pericardial, pleural, or ascites fluid requiring drainage. However, if the fluid can be controlled by oral medication alone, it is acceptable. 4) Grade 2 or higher peripheral neuropathy 5) Brain or meningeal metastases. 5) Patients with brain or meningeal metastases, but brain imaging is not required for asymptomatic patients who do not require treatment. 6) Have synchronous multiple active cancers. 7) Received any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4, or other T-cell regulating antibody or pharmacologic therapy 8) Current or past severe hypersensitivity to other antibody drugs 9) Has a concomitant autoimmune disease or a history of autoimmune disease. Patients with type 1 diabetes mellitus, hypothyroidism manageable with hormone replacement, and dermatological diseases not requiring systemic treatment (vitiligo, psoriasis, alopecia, etc.) may be enrolled. 10) Patients with complications or history of interstitial lung disease or pulmonary fibrosis: diagnosis must be based on CT findings 11) Patients with concomitant diverticulitis or symptomatic gastrointestinal ulcerative disease 12) Using warfarin, phenytoin, or flucytosine at the time of enrollment 13) Received or required systemic corticosteroids (except for temporary use for testing, prevention of allergic reactions, or reduction of edema due to radiation therapy) or immunosuppressive drugs within 28 days prior to enrollment 14) Have transient ischemic attack, cerebrovascular disease, thrombosis, or thromboembolism (pulmonary arterial embolism, deep vein thrombosis) within 180 days prior to enrollment. 15) History of any of the following cardiac diseases Myocardial infarction within 180 days prior to enrollment Uncontrolled angina pectoris within 180 days prior to study enrollment New York Heart Association (NYHA) Class3 or 4 congestive heart failure 16) Uncontrolled diabetes mellitus 17) Systemic infection requiring treatment 18) Underwent surgery (any surgery involving general anesthesia) within 28 days prior to enrollment 19) Had radiotherapy for gastric cancer within 28 days prior to enrollment or radiotherapy for bone metastases within 14 days prior to enrollment 20) Received radiopharmaceuticals within 56 days prior to enrollment (except for use of radiopharmaceuticals for laboratory or diagnostic purposes) 21) Received other unapproved drugs within 28 days (90 days for antibody drugs) prior to study enrollment 22) Positive for human immunodeficiency virus-1 (HIV-1), human immunodeficiency virus-2 (HIV-2), human T lymphotropic virus-1 (HTLV-1), hepatitis B surface protein (HBs) antigen, or hepatitis C virus (HCV) antibody 23) HBs antigen negative but HBs or HBc antibody positive with detectable hepatitis B virus deoxyribonucleic acid (HBV-DNA) 24) Pregnant, lactating, or possibly pregnant 25) Unable to give consent for specific reasons, such as concomitant dementia 26) Has received a live/weakly toxic vaccine within 28 days prior to study enrollment 27) Other individuals deemed inappropriate to participate in this study by the Principal Investigator(s)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1) Safety confirmation part The safety confirmation part will be conducted in the initial 6 patients to evaluate the incidence of dose-limiting toxic DLTs. 2) Expansion part The response rate and survival will be evaluated in all patients, including the 6 patients in the safety confirmation part, by adding additional patients as part of the Phase II single-arm study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Adverse Event Incidence Ratio Relative drug strength of S-1, oxaliplatin, and nivolumab Response rate in patients with measurable disease Disease control rate in patients with measurable disease Progression-free survival Overall survival | — |
Contacts
Public ContactNarikazu Boku
IMSUT hospital, the Institute of Medical Science, The University of Tokyo
Outcome results
None listed