First-line treatment of RAS mutated PMMR /MSS advanced colorectal cancer
Conditions
Interventions
group A :XELOX combined with PD-1 inhibitor and bevacizumab biosimilar
group B :XELOX in combination with bevacizumab biosimilar
Sponsors
the First Medical Center of PLA General Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Gammaglobulin group 1. Sign written informed consent before implementing any trial-related procedures; 2. Aged 18 to 75 years; 3. Histologically or cytologically confirmed inoperable metastatic colorectal cancer (AJCC 8th stage IV) with measurable lesions according to RECIST criteria; 4. KRAS or NRAS mutation, BRAF wild type; 5. pMMR or MSS; 6. Have not received chemotherapy, targeted therapy or immunotherapy before; or more than 12 months from the last adjuvant chemotherapy; 7. ECOG score 0-1 points; 8. Expected survival time > 3 months; 9. Sufficient organ function, subjects should meet the following laboratory indicators: (1) The absolute value of neutrophils (ANC) is >=1.5x10^9/L without the use of granulocyte colony-stimulating factor in the past 14 days; (2) Platelets >=90x10^9/L without blood transfusion in the past 14 days; (3) Hemoglobin > 9g/dL without blood transfusion or erythropoietin in the past 14 days; (4) Total bilirubin =60 ml/min; (7) Good coagulation function, defined as international normalized 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 the baseline TSH exceeds the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled; (9) Myocardial enzyme spectrum is within the normal range (if the investigator comprehensively judges that the simple laboratory abnormality does not have clinical significance, it is also allowed to enter the group); (optional) 10. For female subjects of childbearing age, a negative urine or serum pregnancy test should be performed within 3 days prior to receiving the first dose of study drug (Day 1 of Cycle 1). If a urine pregnancy test result cannot be confirmed negative, a blood pregnancy test is required. Women of non-reproductive age are defined as having been postmenopausal for at least 1 year, or have undergone surgical sterilization or hysterectomy; 11. If there is a risk of conception, all subjects (regardless of male or female) are required to use the drug throughout the treatment period until 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy drug) Low annual failure rate less than 1% of contraceptives.
Exclusion criteria
Exclusion criteria: 1. Symptomatic or high-risk obstruction, bleeding, perforation, pneumonia (including non-infectious pneumonia patients who have received hormone therapy in the past and patients with pneumonia who are receiving treatment), etc.; 2. Patients who underwent intestinal stenting to relieve intestinal obstruction; 3. CNS metastases identified by CT or magnetic resonance assessment during screening, including brain metastases and meningeal metastases; 4. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once every two weeks or more frequently); allow patients to indwell catheters; 5. Patients with uncontrolled hypertension; 6. Uncontrolled or symptomatic hypercalcemia; 7. Those with a history of uncontrollable mental illness; severe intellectual or cognitive impairment; 8. Congestive heart failure, uncontrollable arrhythmia, myocardial infarction, unstable angina pectoris, stroke or transient ischemic attack within 6 months; 9. Diagnosed with other malignant diseases other than colorectal cancer within 5 years before the first administration (excluding basal cell carcinoma of the skin, squamous epithelial carcinoma of the skin, and/or carcinoma in situ after radical resection); 10. Currently participating in interventional clinical research treatment, or have received other investigational drugs or used investigational device treatment within 4 weeks before the first dose; 11. Received systemic systemic treatment of Chinese patent medicines with anti-tumor indications or drugs with immunomodulatory effects (including thymosin, interferon, and interleukin, except for local use for controlling pleural effusion) within 2 weeks before the first administration; 12. Active autoimmune disease requiring systemic therapy (such as the use of disease-modifying drugs, glucocorticoids or immunosuppressants) has occurred within 2 years before the first dose. Replacement therapy (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency, etc.) is not considered systemic therapy; 13. Those who are receiving systemic glucocorticoid therapy (excluding nasal spray, inhalation or other local glucocorticoids) or any other form of immunosuppressive therapy within 7 days before the first dose of the study; Note: Physiological doses of glucocorticoids (<=10 mg/day prednisone or equivalent) are allowed; 14. Receive blood transfusion within 7 days before the first treatment; 15. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 16. Those who are known to be allergic to active ingredients or excipients such as the study drug PD-1 monoclonal antibody, bevacizumab biosimilar (Dayotong), oxaliplatin or capecitabine; 17. Those with multiple factors that affect oral drugs (such as inability to swallow, after gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.); 18. Have not recovered sufficiently from toxicity and/or complications caused by any intervention (ie, <= Grade 1 or reached baseline, excluding fatigue or alopecia) prior to initiation of treatment; 19. Known history of human immunodeficiency virus (HIV) infection; 20. Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number greater than the upper limit of normal in the laboratory department of the research center); Note: Hepatitis B subjects who meet the following criteria can also be enr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| l Progression-free survival (PFS) was compared and assessed according to RECIST1.1 and IRRECIST; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR), time to disease response (DoR), disease control rate (DCR), overall survival (OS), conversion therapy success rate, safety serious adverse event (SAE) rate, and PD-1 single Incidence of immune-related adverse events (irAEs) in the anti-combination arm; | — |
Countries
China
Contacts
Public ContactDai Guanghai
The First Medical Center of PLA General Hospital
Outcome results
None listed