Advanced Solid Tumor
Conditions
Interventions
Cohort with TIL treatment:Reinfusion TIL
Sponsors
the First Affiliated Hospital of Zhengzhou University
Eligibility
Sex/Gender
All
Age
3 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily join the research, sign the informed consent form, and be willing and able to abide by the research protocol; 2. Aged 3 to 70 years (calculated on the day of signing informed consent); 3. Recurrent/metastatic advanced solid tumors with opportunities to obtain tumor tissue (such as through local excision/palliative surgery); 4. After at least one standard treatment, the disease has progressed; and there is no effective treatment option available or refuses to accept further treatment ("effective treatment" refers to the latest version of the diagnosis and treatment guidelines for various cancers); 5. There is at least one resectable tumor lesion (preferably superficial lymph node) that has not received radiation therapy or other local therapy, and at least a tissue block with a volume of >= 0.5 cm3 can be isolated (single lesion source or Multiple lesions combined) for the preparation of autologous tumor-infiltrating lymphocytes; minimally invasive treatment as possible; 6. After tumor sampling, there is at least one measurable lesion that meets the definition of RECIST 1.1 criteria, and this lesion has not received radiotherapy or other local therapy (unless these therapy occurred earlier than 3 months ago, and the lesion shows progression) ; 7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; 8. Expected survival time >= 12 weeks; 9. The function of vital organs meets the following requirements (no blood components and cell growth factor therapy are allowed within 14 days before surgery): Routine blood examination: no cytokine or blood transfusion therapy within 14 days before the test; absolute neutrophil count (ANC)>=1.5x10^9/L; Lymphocyte count (LC)>0.5x10^9/L; Platelet count (PLT)>=100x10^9/L; Hemoglobin (Hb)>=90g/L; Liver function tests: AST, ALT and alkaline phosphatase = 45 mL/ min (Cockcroft-Gault formula can be used), or serum creatinine is within the normal range; coagulation function test: APTT= 50%; Pulmonary function test: FEV1>=60%; 10. Non-surgical sterilization females of childbearing age need to agree to use at least one medically approved contraceptive method (such as intrauterine device, contraceptives or condoms) for contraception during the study treatment period and within 1 year after the end of the study treatment period; Non-surgical sterilized female subjects of childbearing age must have a negative serum HCG test within 7 days before cell reinfusion; 11. Before tumor sampling, the adverse reactions caused by previous treatment have recovered (CTCAE 5.0 <= 1) or can meet the test values ??specified in the test protocol (except for 2nd degree peripheral neuropathy, alopecia, vitiligo/hormone replacement therapy controllable) Hypothyroidism and well-insulin-controlled type 1 diabetes); 6 months of asymptomatic status prior to tumor sampling if documented grade 2 or higher diarrhea or colitis on prior immune checkpoint inhibitor therapy (or safe as assessed by colonoscopy); 12. Prior to tumor sampling, there must be an imaging record
Exclusion criteria
Exclusion criteria: 1. Patients with active central nervous system (CNS) metastases (patients with stable brain metastases, no need for drug treatment within 2 weeks of clinical judgment, except for those without hormone dependence); 2. Surgery and/or radiotherapy fails to relieve spinal cord compression and cannot be included in the group (patients who have been treated can be enrolled if clinical evidence shows that their symptoms have been relieved for >=1 week before surgical sampling); 3. Patients with uncontrolled tumor-related pain as judged by the investigator. Subjects requiring pain medication must have a stable analgesic regimen at the time of entry into the study; symptomatic lesions suitable for palliative radiotherapy should be treated prior to study entry; 4. Suffering from interstitial pneumonia or clinically significant active pneumonia at the time of screening, or other respiratory diseases that seriously affect lung function; 5. Any active autoimmune disease, history of autoimmune disease, or disease requiring systemic steroids or immunosuppressive drugs (>10 mg/day of prednisone or equivalent hormones); 6. A history of significant clinically significant cardiovascular disease, including but not limited to: (1) Congestive heart failure (NYHA class>2); (2) Unstable angina; (3) Myocardial infarction has occurred in the past 3 months; (4) Any supraventricular arrhythmia or ventricular arrhythmia requiring treatment or intervention; 7. Arterial/venous thrombotic events that occurred within 5 months before enrollment, such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism; 8. Those who have active pulmonary tuberculosis infection within 1 year before enrollment, or those who have a history of active pulmonary tuberculosis infection more than 1 year ago but have not received regular treatment; 9. Active infection requiring systemic anti-infective treatment (except topical antibiotics) or unexplained fever >38.5? during screening, except tumor fever; 10. History of immunodeficiency, including HIV seropositive; 11. Active hepatitis B or C patients. HBsAg or HBcAb positive patients can participate in this study if the HBV DNA test is less than the lower limit of the normal value in the research center. HCV antibody-positive patients can participate in this study if the HCV RNA detection is less than the lower limit of the normal value detected by the research center. Carriers participating in the study should arrange antiviral treatment as appropriate, and periodically review the nucleic acid copy number quantitative detection during the study period; 12. Refractory or intractable epilepsy, active gastrointestinal bleeding, IL-2 allergy or contraindications to IL-2 use (see 4.2.3 for details); 13. Use of live attenuated vaccines within 4 weeks before enrollment, or use of live attenuated vaccines during the study period; 14. Use anti-angiogenesis drugs with long half-life, such as VEGF bevacizumab, within the first four weeks of enrollment; 15. Patients who have received allogeneic bone marrow transplantation or solid organ transplantation in the past; 16. Drugs to be used in the study (including but not limited to autologous tumor-infiltrating lymphocytes, cyclophosphamide, fludarabine, interleukin-2, dimethyl sulfoxide (DMSO), human serum albumin (HSA) history of allergic reaction to any component of , dextran-40 (dextran-40), antibiotics (beta-lactam antibiotics, gentamicin)); 17. Known mental illness
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety and tolerance; | — |
Secondary
| Measure | Time frame |
|---|---|
| objective response rate;disease control rate;progression-free survival;response period;overall survival; | — |
Countries
China
Contacts
Public ContactZhang Yi
the First Affiliated Hospital of Zhengzhou University
Outcome results
None listed