Advanced colorectal cance
Conditions
Interventions
Experimental group:Sindilizumab combined with bevacizumab +TAS-102
Sponsors
Zhejiang Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Sign a written informed consent before implementing any procedures related to the trial; 2. Age =18 years old; 3. Histologically or cytologically proven inoperable metastatic colorectal cancer (AJCC 8th is stage IV); 4. Disease progression during or after previous oxaliplatin/irinotecan/fluorouracil ± targeted drug therapy (RECIST v1.1); 5. According to the solid tumor efficacy evaluation criteria (RECIST 1.1 edition), there is at least one radiographically measurable lesion; 6.ECOG score 0-1; 7. Expected survival time >3 months; 8. For adequate organ function, subjects must meet the following laboratory criteria: 1) Neutrophil absolute value (ANC) =1.5x109/L in the last 14 days without the use of granulocyte colony-stimulating factor. 2) Platelets =90× 109/L in the past 14 days without blood transfusion. 3) In the case of no blood transfusion or use of erythropoietin in the past 14 days, blood red and egg white >9g/dL; 4) Total bilirubin =1.5 × upper limit of normal (ULN); Or total bilirubin >ULN but direct bilirubin = ULN; 5) Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =5×ULN (ALT or AST =5×ULN in patients with liver metastasis); 6) Serum creatinine = 1.5 ×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) =60 ml/min; 7) Good coagulation function, defined as International standardized ratio (INR) or prothrombin time (PT) =1.5 times ULN; 8) Normal thyroid function, defined as thyroid stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled; 9) The myocardial enzyme profile was within the normal range (if the researcher comprehensively judged that the simple laboratory abnormality was not clinically significant, it was also allowed to be included); (Optional); 9. For female subjects of reproductive age, a urine or serum pregnancy test should be performed within 3 days prior to receiving the first study drug administration (day 1 of cycle 1) and the results are negative. If the urine pregnancy test results cannot be confirmed as negative, a blood pregnancy test is requested. Women of non-reproductive age were defined as at least one year after menopause or having undergone surgical sterilization or hysterectomy; 10. If there is a risk of conception, all subjects (male or female) are required to use contraception with an annual failure rate of less than 1% for the entire treatment period up to 120 days after the last study drug administration of treatment (or 180 days after the last chemotherapy drug administration).
Exclusion criteria
Exclusion criteria: 1. Previous treatment with anti-PD-1, anti-PD-L1, anti-PD-L2 drugs or drugs that target another stimulus or synergistically inhibit T cell receptors (e.g., CTLA-4, OX-40, CD137) (adjustable); 2. Symptomatic or high-risk obstruction, bleeding, perforation, pneumonia (including noncommunicable pneumonia patients who have previously received hormonal therapy and pneumonia patients under treatment); 3. Malignant diseases other than colorectal cancer diagnosed within 5 years prior to initial administration (excluding basal cell carcinoma of the skin, squamous epithelial carcinoma of the skin, and/or carcinoma in situ after radical resection); 4. Is currently participating in an interventional clinical study, or has received other investigational drugs or used investigational devices within 4 weeks prior to initial dosing; 5. Had surgery within 6 weeks before the first dose. 6. Received any anti-tumor therapy (including chemotherapy, targeted therapy, radiotherapy, interventional therapy, etc.) within 2 weeks before the first dose; Chinese patent drugs with anti-tumor indications or immunomodulatory effects (including thymosin, interferon, interleukin, except for local use to control pleural fluid) systemic systemic treatment; 7. An active autoimmune disease requiring systemic treatment (e.g. with disease-modifying drugs, glucocorticoids, or immunosuppressants) has occurred within 2 years prior to first administration. Replacement therapy (e.g., thyroxine, insulin, or physiologic glucocorticoids for adrenal or pituitary insufficiency) is not considered systemic therapy; 8. Was receiving systemic glucocorticoid therapy (excluding nasal, inhaled, or other local glucocorticoids) or any other form of immunosuppressive therapy within 7 days prior to the initial administration of the study; Note: The use of physiological doses of glucocorticoids (=10 mg/ day of prednisone or equivalent) is permitted; 9. Clinically uncontrollable pleural effusion/abdominal effusion (patients who do not need to drain effusion or who have no significant increase in effusion after 3 days of stopping drainage can be enrolled); 10. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 11. Those who are known to be allergic to sindilizumab, bevacizumab, TAS-102 active ingredients or adjuvants of this study; 12. Persons with multiple factors affecting oral medication (such as inability to swallow, severe chronic diarrhea, and intestinal obstruction); 13. Has not fully recovered from the toxicity and/or complications caused by any intervention before starting treatment (i.e., = grade 1 or baseline, excluding weakness or hair loss); 14. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive); 15. Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number detected greater than the upper limit of normal value in the laboratory of the study center); Note: Hepatitis B subjects who meet the following criteria can also be enrolled: 1) HBV viral load <1000 copies /ml (200 IU/ml) before the first dose, 2) Prophylactic anti-HBV therapy is not required for subjects with anti-HBC (+), anti-HBSAG (-), anti-HBS (-), and HBV viral load (-). However, virus reactivation needs to be closely monitored; 16. Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection); 17. Received live vaccine within 30 days prior to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| safety;DCR( disease control rate);DoR(duration of response);mPFS(median progression free survival);OS(overall survival); | — |
Countries
China
Contacts
Public ContactJunchi Cheng,Xiaohong Wang
Zhejiang Cancer Hospital
Outcome results
None listed