hepatocellular carcinoma
Conditions
Interventions
Experimental group:Tirelizumab combined with TKI therapy, after disease control, patients with further progression were treated with intestinal flora transplantation based on the original regimen
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age: 18-75 years, male or female; 2. Clinically or pathologically confirmed unresectable primary hepatocellular carcinoma; 3. Liver cancer patients with BCLC stage B or C; 4. Progression or intolerance after prior first-line treatment with TKI monotherapy or TKI combined with immunotherapy; 5. No prior immunotherapy, including PD-L1 or CTLA-4 inhibitors, has been administered; 6. Subject must have at least 1 measurable target lesion examined by CT or MRI according to RECIST1.1 criteria; 7. The Eastern Oncology Consortium (ECOG) Behavioral status score was 0 or 1; 8. ChildPugh A/B (= 9.0 g/dl, neutrophils absolute value >= 1.5 x 10^9/L, PLT >= 50 x 10^9/L, serum ALB >= 28 g/L, TBIL < 34 umol/L, ALT and AST < 5 times the upper limit of normal value, BuN and Cr < 1.5 times the upper limit of normal value, INR < 2.3 or PT lengthening < 6 s; 12. Women of childbearing age and men with partners of childbearing age are required to use contraception within 120 days after the last medication. 13. The subjects voluntarily joined the study, signed the informed consent, complied well, and cooperated with follow-up visits.
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating women; 2. Previous immune-related therapy, including PD-L1, or CTLA-4 inhibitors; 3. Failure to recover from toxicity and/or complications of previous interventions to NCI-CTCAE 10 mg/ day equivalent of prednisone) or other immunosuppressive agents within 14 days prior to PD-1 monoclonal antibody were challenged. The following are excluded: (1) In the absence of active autoimmune disease, inhaled, ophthalmic, or topical steroids and adrenocortical corticosteroids at doses not exceeding the therapeutic dose of 10 mg/day prednisone are permitted; (2) The dosage of systemic glucocorticoids of physiological dose does not exceed 10 mg/day prednisone or equivalent dose of other glucocorticoids; (3) Glucocorticoids are used as prophylactic drugs for hypersensitivity reactions (such as medication before CT examination and pretreatment before chemotherapy); 5. The challenge was to have received abdominal radiotherapy and taken radioactive substances within 28 days before the use of PD-1 monoclonal antibody; 6. A history of gastrointestinal perforation and/or fistula within 6 months prior to the use of PD-1 mab; 7. There was active gastrointestinal bleeding 1 week before the first microflora transplantation. Only patients with positive fecal occult blood, no black stool, bloody stool are excluded, only haemorrhoid bleeding is excluded; 8. Infections occurring within 28 days prior to the use of PD-1 mab, including but not limited to complications requiring hospitalization, sepsis, or severe pneumonia; 9. Before the use of PD-1 monoclonal antibody and intestinal flora transplantation, there were active infections with systemic treatment, and systemic anti-infection treatment was required, except for local infections requiring only local antibiotics, such as skin infections; 10. Those who received live or attenuated vaccine within 30 days prior to the use of PD-1 monoclonal antibody, or who planned to receive the vaccine during the study period; 11. Known history of primary immunodeficiency virus infection; 12. Active or previously documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis, chronic diarrhea). Patients with chronic diarrhea without recurrence within 2 years prior to enrollment were excluded; 13. There is a known history of active tuberculosis (TB). Subjects suspected of active TB should be examined by chest CT or X-ray, sputum, and excluded by clinical signs and symptoms; 14. Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation; 15. Has an active, known or suspected autoimmune disease, or a history of autoimmune disease; 16. History of cardiovascular or cerebrovascular events or accidents within the past 6 months; 17. A known mental illness or substance abuse that would interfere with compliance with test requirements; 18. Any condition that the investigator considers likely to result in a risk for acceptance of the study treatment or to interfere with the evaluation of the study treatment or with the safety of the subjects or the interpretation of the study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease control rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival;Progression Free Survival;Objective Remission Rate;Incidence and severity of adverse events;Index of intestinal flora change;Index of tumor immune microenvironment change; | — |
Countries
China
Contacts
Public ContactXin Wang
West China Hospital of Sichuan University
Outcome results
None listed