Advanced Solid Tumor
Conditions
Interventions
Experimental group:Infusion of autologous tumor-infiltrating lymphocytes (TILs)
Sponsors
Fujian Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 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 18 to 70 years (calculated on the day of signing the informed consent); 3. Diagnosed as: (1) Hepatocellular carcinoma confirmed by histopathology or cytology (classified as stage II-III according to Chinese liver cancer stage (CNLC stage), or stage B/C according to Barcelona clinical liver cancer (BCLC) stage), and not suitable for surgery or local therapy; and histopathologically confirmed (intrahepatic) bile duct cells; (2) Unresectable recurrent or metastatic melanoma (stage III-IV); (3) Other unresectable recurrent/metastatic advanced solid tumors; 4. Pre-treatment requirements: (1) Progress through TACE (hepatic arterial chemoembolization) and systemic therapy (targeted or immunotherapy); (2) Disease progression after at least second-line therapy listed below: disease progression within 6 months after the end of any systemic chemotherapy (such as dacarbazine) or adjuvant chemotherapy for the treatment of recurrent or metastatic melanoma, targeted drugs (such as BRAF inhibitors, BRAF+MEK inhibitor combination), immune checkpoint inhibitors (such as PD-1 monoclonal antibodies); (3) The disease has progressed after at least one pre-sequence standard treatment; and there is no effective treatment option available at present (for effective treatment, please refer to the latest edition of the diagnosis and treatment guidelines for various cancer types); 5. At least one resectable tumor lesion (preferably superficial lymph node) that has not received radiotherapy and other local therapy, and at least a tissue block with a volume of >=0.5cm^3 can be isolated (from a single lesion or a combination of multiple lesions) for the preparation of autologous tumor-infiltrating lymphocytes; minimally invasive treatment is possible; 6. After tumor sampling, there is at least one measurable lesion that meets the definition of RECIST v1.1 criteria, and the lesion has not received radiotherapy or other local therapy (unless these therapies occurred earlier than 3 months ago and the lesion showed progression); 7. The Eastern Cooperative Oncology Group (ECOG) performance status score is 0 or 1, and cohort 1 also needs to meet the Child-Pugh liver function rating of A (= 12 weeks; 9. The function of vital organs meets the following requirements (the use of any blood components and cell growth factor therapy is not allowed within 14 days before surgery): (1) Routine blood test: (without receiving cytokines or blood transfusion within 14 days before the test) absolute neutrophil count (ANC) >= 1.5x10^9/L, lymphocyte count (LC) >= 0.5x10^9/L, platelet count (PLT) >= 80x10^9/L, hemoglobin (Hb) >= 90g/L; (2) Liver function test (cohort 1 according to the requirements of liver metastasis): AST, ALT and alkaline phosphatase = 45 mL/min (Cockcroft-Gault formula can be used), or serum creatinine is within the normal range; (4) Coagulation function test: APTT <= 1.5xULN, and INR or PT<=1.5xULN; (5
Exclusion criteria
Exclusion criteria: 1. Patients with hepatic encephalopathy or active central nervous system (CNS) metastasis (patients with stable brain metastasis, no need for drug treatment within 2 weeks according to 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. patients requiring analgesic 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 entry into the study; 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 steroid hormones or immunosuppressive drugs (>10 mg/day of prednisone or equivalent hormones); 6. 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 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. A 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 conduct regular review during the study period for quantitative nucleic acid copy number detection; 12. Refractory or intractable epilepsy, ascites that cannot be controlled by drugs, portal vein tumor thrombus, gastrointestinal bleeding caused by fundus or esophageal varices, increased risk of bleeding caused by portal hypertension, active gastrointestinal bleeding, etc.; 13. Use of live attenuated vaccines within 4 weeks before enrollment, or use of live attenuated vaccines during the study period; 14. Use anti-angiogenic drugs with long half-life, such as VEGF bevacizumab, within four weeks before enrollment; 15. Patients who have received allogeneic bone marrow transplantation or solid organ transplantation in the past; 16. History of allergic reaction to any component of the drug to be used in the study (including but not limited to autologous tumor-infiltrating lymphocytes, cyclophosphamide, fludar
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety and tolerance;objective response rate;disease control rate;progression-free survival;response period;overall survival; | — |
Countries
China
Contacts
Public ContactLi Jingfeng, Chen Yu
Outcome results
None listed