adenocarcinoma of esophagogastric junction
Conditions
Interventions
Dose-escalation phase:Escalating-dose of SmarT+PD-1 mAb+low dose radiotherapy
Expansion phase-cohortA:Recommended dose of SmarT+PD-1mAb+oxaliplatin+S-1+low dose radiotherapy
Expansion phase-cohortB:PD-1mAb+oxaliplatin+S-1
Sponsors
Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. The subjects can understand the informed consent form, voluntarily participate in and sign the informed consent form; 2. Subjects >= 18 years old on the day of signing informed consent; 3. The eastern United States cancer collaboration group physical state score (ECOG) is 0-1; 4. Estimated survival >= 12 weeks; 5. Dose increasing stage: solid tumor patients who fail to receive first-line or standard treatment (disease progression or intolerable toxic and side effects after treatment) or have no effective treatment; Dose amplification stage: previously untreated metastatic or locally advanced unresectable adenocarcinoma of the stomach or gastroesophageal junction confirmed by histology or cytology. For subjects who had previously received neoadjuvant / adjuvant chemotherapy or chemoradiotherapy for radical purposes, the time between disease progression and the last treatment was at least 6 months; 6. At least one assessable lesion at baseline can be used for efficacy evaluation; 7. All subjects must provide tumor tissue samples archived or freshly obtained within 2 years before signing. At least 5 unstained tumor tissue slice samples, preferably newly obtained tumor tissue samples; 8. Knowing the advantages and disadvantages of standard treatment, he is still unwilling to accept standard treatment; 9. The patient has adequate organ and bone marrow function, which is defined as follows: Blood routine: neutrophil count >= 1.5 x 10^9 / L, hemoglobin >= 8.0g/dl, platelet count >= 75 x 10^9/L Liver function: total bilirubin <= 1.5 x Upper limit of normal value (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 2.5 in subjects without liver metastasis x ULN Requirements for subjects with liver metastasis: ALT and AST <= 5 x ULN Renal function: serum creatinine (SCR) <= 1.5 x ULN Adequate coagulation function: defined as international normalized ratio (INR) <= 1.5 or prothrombin time (PT) <= 1.5 times ULN; If the subject is receiving anticoagulant therapy, as long as Pt is within the scope of anticoagulant drug formulation; 10. Patients of childbearing age need to take appropriate protective measures (contraceptives or other methods of birth control) before enrollment and in the trial; 11. Informed consent has been signed, and the visit and relevant procedures specified in the scheme can be followed.
Exclusion criteria
Exclusion criteria: 1. Uncontrollable pleural effusion, pericardial effusion and peritoneal effusion shall be excluded (drainage shall be conducted at least once a month); 2. Dose expansion stage: for subjects with known HER2 positive gastric or gastroesophageal junction adenocarcinoma, if the HER2 status is unknown, the HER2 status needs to be detected in the screening stage. Palliative local treatment for non target lesions within 2 weeks before the first administration; Received systemic nonspecific immunomodulatory therapy (such as interleukin, interferon, thymosin, etc.) within 2 weeks before the first administration; Received Chinese herbal medicine or proprietary Chinese medicine with anti-tumor indications within 2 weeks before the first administration. In the past, he has received immune checkpoint inhibitors (such as anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists (such as antibodies against ICOS, CD40, CD137, GITR, OX40 targets, etc.), immune cell therapy and any treatment against tumor immune mechanism; 3. The patient has a history of other tumors, except for cervical cancer in situ, treated squamous cell carcinoma or bladder epithelial tumors (TA and TIS) or other malignant tumors that have received radical treatment (at least 5 years before enrollment); 4. Uncontrollable concomitant diseases, including but not limited to active bacterial or fungal infection, symptomatic congestive heart failure, unstable angina pectoris and arrhythmia; 5. Accompanied by HIV infection or active hepatitis B, HBV (HBV DNA >= 500iu / mL), hepatitis C; 6. Uncontrollable coronary artery disease or asthma, uncontrollable cerebrovascular disease or other diseases considered by the researchers to be out of the group; 7. Uncontrollable concomitant diseases, including but not limited to active bacterial or fungal infection, congestive heart failure, unstable angina pectoris, arrhythmia, etc. A poorly controlled arrhythmia. History of congenital long QT syndrome or corrected QTc at screening > 500ms (calculated by fridericia method); 8. Subjects with autoimmune diseases or immune deficiencies; 9. Immunosuppressive drugs were used within 4 weeks before the first administration of the study drug, excluding a) intranasal inhaled local steroid therapy or local steroid injection (such as intra-articular injection); b) Systemic corticosteroid treatment not exceeding 10 mg/day prednisone or its equivalent physiological dose; c) Glucocorticoid is used as a preventive drug for allergic reaction (such as medication before CT); 10. Subjects requiring long-term systemic hormone or any other immunosuppressive drugs, excluding inhaled hormone therapy; 11. Receive live attenuated vaccine within 4 weeks before the first administration of the study drug or plan to receive the live attenuated vaccine during the study period; 12. Major surgery (craniotomy, thoracotomy, or laparotomy) was performed within 4 weeks prior to the first dose of study treatment, or major surgery is expected to be required during the study treatment; 13. A history of gastrointestinal perforation and/or fistula, intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive intestinal resection (partial colectomy or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis or long-term chronic diarrhea within the past 6 months; 14. Subjects with gastrointestinal bleeding or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate;Progression-Free-Survival;Safety;Maximal Tolerable Dose; | — |
Countries
China
Contacts
Public ContactBaorui Liu
Outcome results
None listed