Colorectal cancer
Conditions
Interventions
test group:Sintilizumab combined with bevacizumab
Sponsors
The First Affiliated Hospital of Guangxi Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Sign written informed consent before implementing any test related process; 2. Aged >=18 years old; 3. Inoperable metastatic colorectal cancer confirmed by histology or cytology (AJCC 8th is stage IV); 4. If disease progression occurs during or after first-line standard treatment (RECIST v1.1), the first-line standard regimen can be chemotherapy ± bevacizumab / cetuximab; 5. According to the evaluation criteria of solid tumor efficacy (RECIST version 1.1), at least one imaging measurable lesion; 6. Patients with brain metastases who are asymptomatic or have stable symptoms after local treatment are allowed to be included as long as the patients meet the following conditions: 1) Measurable lesions outside the central nervous system 2) No central nervous system symptoms or no aggravation of symptoms for at least 2 weeks 3) Those who do not need glucocorticoid treatment or stop glucocorticoid treatment within 7 days before the administration of the first study drug 7. Subjects are allowed to receive palliative radiotherapy (including craniocerebral radiotherapy for symptomatic brain metastases), but the radiotherapy should be completed at least 1 week before enrollment, and the radiation-related toxicity should be restored to less than or equal to 1 degree (CTCAE 5.0, except hair loss); 8. ECoG score: 0-1; 9. Expected survival time > 3 months; 10. adequate organ function, subjects need to meet the following laboratory indicators: 1) The absolute value of neutrophils (ANC) >=1.5x10^9/l without granulocyte colony stimulating factor in recent 14 days. 2) Platelets >=90 without blood transfusion in recent 14 daysx10^9/L 3) Hemoglobin > 9g / dl without blood transfusion or erythropoietin in recent 14 days; 4) Total bilirubin ULN but direct bilirubin =60 ml / min; 7) Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) <=1.5 ULN; 8) Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If baseline TSH exceeds the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled; 9) The myocardial enzyme spectrum is within the normal range (if the researcher comprehensively judges that simple laboratory abnormalities without clinical significance are also allowed to be included in the group); (optional) 11. For female subjects of childbearing age, Urine or serum pregnancy test should be performed within 3 days before the first study drug administration (day 1 of cycle 1) and the result is negative. If the urine pregnancy test result cannot be confirmed as negative, blood pregnancy test is required. Women of non childbearing age are defined as at least 1 year after menopause, or have undergone surgical sterilization or hysterectomy; If there is a risk of pregnancy, all subjects (male or female) are required to use contraceptives with an annual failure rate of less than 1% throughout the treatment period until 120 days after the last study drug administration (or 180 days after the last chemotherapy drug administration).
Exclusion criteria
Exclusion criteria: 1. Have previously received the following therapies: anti-pd1 drugs, anti-PD-L1, anti-PD-L2 drugs or drugs that stimulate or co inhibit T cell receptors (e.g., CTLA-4, OX-40, CD137) (adjustable); 2. Symptomatic or high-risk obstruction, bleeding, perforation, pneumonia (including non communicable pneumonia previously treated with hormone and pneumonia patients being treated); 3. Other malignant diseases other than colorectal cancer diagnosed within 5 years before the first administration (excluding radical skin basal cell carcinoma, skin squamous epithelial carcinoma, and / or radical resection of carcinoma in situ); 4. Currently participating in intervention clinical research treatment, or receiving other research drugs or using research instruments within 4 weeks before the first administration; 5. Received systemic treatment with Chinese patent medicine with anti-tumor indications or drugs with immunomodulatory effect (including thymosin, interferon and interleukin, except for local use to control pleural effusion) within 2 weeks before the first administration; 6. Active autoimmune diseases requiring systemic treatment (such as disease relieving drugs, glucocorticoids or immunosuppressants) occurred within 2 years before the first administration. Alternative therapies (such as thyroxine, insulin or biological glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic treatment; 7. Being treated with systemic glucocorticoids (excluding local glucocorticoids by nasal spray, inhalation or other means) or any other form of immunosuppressive therapy within 7 days before the first administration of the study; Note: it is allowed to use glucocorticoids in physiological doses (= 10 mg / day prednisone or equivalent); 8. Receive blood transfusion within 7 days before the first treatment; 9. There is clinically uncontrollable pleural effusion / peritoneal effusion (patients who do not need to drain effusion or stop drainage for 3 days and have no significant increase in effusion can be included in the group); 10. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 11. Those who are known to be allergic to the active ingredients or excipients of cindilimab and bevacizumab; 12. Those with multiple factors affecting oral drugs (such as inability to swallow, post gastrointestinal resection, chronic diarrhea and intestinal obstruction); 13. Not fully recovered from toxicity and / or complications caused by any intervention before starting treatment (i.e. <=grade 1 or reaching baseline, excluding fatigue 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 at the same time was higher than the upper limit of normal value in the laboratory of the research center). Note: hepatitis B patients who meet the following criteria can also be enrolled: 1) Before the first administration, the HBV viral load was less than 1000 copies / ml (200 IU / ml). Subjects should receive anti HBV treatment throughout the study chemotherapy treatment to avoid virus reactivation 2) For subjects with anti HBC (+), HBsAg (-), anti HBS (-) and HBV viral load (-), preventive anti HBV treatment is not required, but virus reactivation needs to be closely monitored 16. Active HCV infected subjects (HC
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease-free survival; | — |
Secondary
| Measure | Time frame |
|---|---|
| Security;Objective response rate;Disease control rate;Duration of remission;Overall survival; | — |
Countries
China
Contacts
Public ContactMa Jie
The First Affiliated Hospital of Guangxi Medical University
Outcome results
None listed