Gastrointestinal neoplasms
Conditions
Interventions
experimental group:CAR-T+Oncolytic adenovirus
Sponsors
The Affiliated Hospital of Xuzhou Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Inclusion criteria
Inclusion criteria: [1] Patients or their legal guardians voluntarily participate and sign informed consent; [2] Age =18 years old and =70 years old; [3]ECOG score 0-1 and expected survival greater than 12 weeks; [4] Histologically proven unresectable, recurrent and/or metastatic refractory digestive system malignancies (including gastrointestinal tumors, pancreatic tumors, liver tumors, and biliary tract tumors) that are positive for B7H3 by immunohistochemical detection, and the positive rate of B7-H3 antigen in tumor tissues is =30%; [5] Received at least first-line treatment after diagnosis of digestive system tumor, including disease recurrence/progression during first-line treatment; Recurrent progression definition (if any of the following conditions are met) : 1) Clearly documented imaging progress 2) CEA, CA19-9, and CA72-4 were continuously elevated (confirmed after 1 week), accompanied by clinical symptoms or physical examination indicating disease progression [6] Have at least one measurable lesion (as required by RECIST v1.1); [7] The patient's vital tissues and organs function well, meeting the following requirements: ? Blood routine: ANC=1.5×109/L; PLT=80×109/L; HGB=80g/L (must not have received growth factor or blood transfusion support within 14 days prior to laboratory examination) ? Blood biochemistry: total bilirubin =2×ULN; ALT and AST=2.5 x ULN; ALT and AST can be enlarged to =5×ULN and total bilirubin =3×ULN in patients with disease (such as liver cancer, liver metastasis, or bile duct obstruction) or Gilbert syndrome. Serum creatinine =1.5 ULN, creatinine clearance >50 mL/min/1.73m2 (according to Cockcroft-Gault formula) ? Lung function: indoor oxygen saturation =95% ? Coagulation function: INR< 1.5x ULN, PT, APTT< 1.5x ULN ? Cardiac function: Left ventricular ejection fraction (LVEF) =40%. [7] Non-surgical sterilization or women of reproductive age are required to use a medically approved contraceptive method after signing informed consent, during the study treatment, and within 8 weeks after the end of the study treatment; Blood HCG tests must be negative for women of reproductive age who were not surgically sterilized within 72 hours prior to study randomization. And must be non-lactation period; [8] As determined by the investigator, the subject needs to return to an acceptable baseline state from all toxicities associated with prior treatment or to a level 0 or 1 of the NCI CTCAE 5.0 scale for related toxicities; Toxicities, such as alopecia and vitiligo, were excluded if the investigator judged that they did not increase the safety risk of drug reinfusion in subsequent studies.
Exclusion criteria
Exclusion criteria: [1] Received the following antitumor therapy prior to blood collection: 1) Receive cytotoxic therapy within 14 days 2) Received experimental drug treatment within 28 days (if the above treatment is also experimental drug treatment, according to the 28-day washout period) 3) Receive immunomodulator therapy within 7 days 4) Received targeted therapy within 28 days [2] Prior receipt of CAR T cell therapy or other cell therapy or therapeutic tumor vaccine against any target; [3] Infectious diseases such as hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection outside the normal reference value range; Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA positive; Human immunodeficiency virus (HIV) antibody positive; Syphilis positive; Active tuberculosis; [4] Have a serious underlying medical condition, such as: 1) There is evidence of a severe active viral, bacterial or uncontrolled systemic fungal infection 2) An active or unstable autoimmune disease or an autoimmune disease that has occurred within 3 years and is likely to recur 3) There is clear clinical evidence of apparent dementia or altered mental status [5] High allergy or history of severe allergy; [6] Complicated with dysfunction of heart, lung, brain, liver, kidney and other important organs; [7] Patients with previous (within 6 months) gastrointestinal perforation, abdominal abscess, or intestinal obstruction or imaging or clinical symptoms indicating intestinal obstruction; [8] Have clinical cardiac symptoms or conditions that are not well controlled, such as: (1) New York Heart Association (NYHA) Grade 2 or higher heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, (4) atrial fibrillation: Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention (5) PR interval >250ms or QTc>250ms; [9] Abnormal coagulation function (INR>2.0 or prothrombin time PT>16s), have a tendency to bleed or are receiving thrombolytic or anticoagulant therapy (allowing prophylactic use of low-dose aspirin, low-molecular weight heparin); [10] Patients with chronic conditions requiring treatment with systemic corticosteroids or other immunosuppressants who have received systemic corticosteroids (=30 mg prednisone or equivalent doses of other corticosteroids) or other immunosuppressants within 30 days prior to blood collection, except for the following: Treatment with topical, ocular, intraarticular, intranasal, and inhaled corticosteroids; Short-term use of glucocorticoids for preventive treatment (e.g. to prevent hypersensitivity to contrast media); [11] The toxic effects of previous antitumor therapy have not returned to the National Cancer Institute General Terminology Standard for Adverse Events (CTCAE 5.0) = Grade 1, except for alopecia or grade 2 peripheral neuropathy; [12] Malignant tumors other than gastric cancer, bowel cancer, pancreatic cancer, liver cancer, and biliary tract tumors that have been diagnosed or treated; [13] Patients with central nervous system metastasis; [14] Women who are pregnant or breastfeeding, or who have a pregnancy plan within six months; [15] Patients identified by the investigator had difficulty completing all visits or procedures required by the study protocol (including the follow-up period), or had insufficient compliance to participate in the study; Or any c
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety; | — |
Countries
China
Contacts
Public ContactLi Li
The Affiliated Hospital of Xuzhou Medical University
Outcome results
None listed