Microsatellite Stable Advanced Metastatic Colorectal Cancer
Conditions
Interventions
Test group :receiving EBRT plus Sintilimab+Furoquentinib triple therapy
Sponsors
The Fifth Affiliated Hospital of Sun Yat-sen University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: (1) Voluntarily signed the informed consent to participate in this observational study. (2) 18 years=Age=75 years. (3)A patient with advanced metastatic MSS/pMMR colorectal cancer was diagnosed by histopathology, immunohistochemistry, and imaging of the primary lesion. (4)mCRC patients with recurrent or metastatic MSS/pMMR who have failed or cannot tolerate second-line chemotherapy.Specifically, patients with recurrent or metastatic mCRC who have previously received standard second-line colorectal cancer treatment scheme (single or combined drugs include Oxaliplatin, irinotecan, 5-Fu or, Capecitabine, Bevacizumab, Cetuximab, etc.), and who have experienced disease progression (PD) during treatment,Or those who have been effectively treated with second-line standard therapy (CR/PR/SD) and have experienced disease progression after receiving treatment for = 4 cycles,Or Patients who experience intolerable toxicity during or after treatment. (5)According to the criteria for evaluating the efficacy of solid tumors (RECIST v1.1), subjects have at least two measurable liver/lung metastases confirmed by CT or MRI;Measurable lesions should not have received local treatment such as radiotherapy (lesions located within the previous radiotherapy area, if confirmed to have progressed, can also be targeted). (6)Toxicity should recover to =grade 1 (according to NCI-CTCAE v5.0 criteria) if patients had received anti-tumor treatment. (7)Asymptomatic patients with brain metastases or those with stable symptoms after local treatment are allowed to be included in the group,Patients need to meet the following conditions:1) Measurable lesions outside the central nervous system;2) No central nervous system symptoms or no worsening of symptoms within at least 2 months;3) Those who do not require glucocorticoid treatment or discontinue glucocorticoid treatment within 3 days before the first study drug administration. (8)Patients are allowed to undergo primary radiotherapy in the past, but the radiotherapy ends 7 days before the first study drug administration. (9)Eastern Cooperative Oncology Group performance status of 0-1. (10)Expected survival time>3 months; (11)Adequate organ function: a. Blood routine examination (no blood transfusions, no hematopoietic stimulators, or no other medications to correct blood counts was administered within 14 days prior to initial treatment): absolute neutrophil count=1.5×10^9/L, platelet count=75×10^9/L, hemoglobin=90 g/L. b. Blood biochemistry: serum creatinine =1.5 upper limit of normal (ULN) or creatinine clearance rate =50mL/min, total bilirubin=1.5 ULN, alanine transaminase and aspartate transaminase=2.5 ULN. c. Coagulation function (no anticoagulant or other medication correction affecting clotting within 14 days prior to initial study administration, except in the case of long-term anticoagulant use due to the subjects' disease): activated partial thrombin time (APTT) and international standardized ratio (INR) =1.5 UNL. d.Normal thyroid function is defined as Thyroid-stimulating hormone (TSH) within normal range.The myocardial enzyme spectrum is within the normal range. (12)Women of childbearing age must agree to take sufficient contraceptive measures within 6 months from the signing of the informed consent form until the last dose. Non childbearing age women are defined as at least 1 year after menopause,Or had undergone surgical sterilization or Hysterectomy.
Exclusion criteria
Exclusion criteria: (1) With uncontrollable allergic asthma and/or a history of allergy to sintilimab and/or bevacizumab and/or their excipients. (2) With other malignancies that have progressed or require treatment within 5 years before enrollment screening (excluding fully treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or cured carcinoma in situ, such as carcinoma in situ of the breast, etc.) (3) Patients with active autoimmune disease or a history of autoimmune disease, but allow further screening for patients with well-controlled type 1 diabetes mellitus, well-controlled thyroid function regression by hormone replacement therapy, and skin disease that does not require systemic treatment (eg, vitiligo, psoriasis, or alopecia), or patients whose disease will not recur in the absence of external triggers. (4) History of primary immunodeficiency. (5) With Severe cardiovascular disease, including but not limited to: New York Heart Association (NYHA) grade 2 and above heart failure; and viral myocarditis, myocardial infarction, poorly controlled heart rhythm and unstable angina pectoris within 3 months prior to screening; severe arterial/venous events (such as transient ischemic attack, cerebral hemorrhage, cerebral infarction, deep vein thrombosis and pulmonary embolism, etc.) within 3 months before screening; cardiac ejection fraction below 50% or the lower limit of the reference range for laboratory tests in the study center; persistent cardiomyopathy, QTc >450 millisecond, or congenital long QT syndrome. (6) Patients with interstitial lung disease (except for localized interstitial pneumonitis induced by radiotherapy) and non-infectious pneumonitis requiring glucocorticoid therapy. (7) With a history of active tuberculosis. (8) Patients with untreated central nerve system metastases, or treated but still symptomatic central nerve system metastases (except for residual signs or symptoms associated with central nerve system treatment, those with stable or improved neurological symptoms at least 2 weeks prior to screening can also be enrolled). (9)Have received any other antibodies/drugs (including PD-1, PD-L1, PD-L2, CTLA-4, OX40, C137 inhibitors, etc.) that act on T cell co stimulation or checkpoint pathways.(10)A history of immune-related adverse events =grade 3 according to NCI-CTCAE v5.0 while receiving immunotherapy in the past. (11) A history of major surgery or radical radiotherapy within 28 days before this study treatment; or palliative radiotherapy within 14 days before the study treatment; or radiopharmaceuticals (strontium, samarium, etc.) within 56 days before the study. (12) A history of receiving systemic anti-tumor therapy 28 days before the study, including but not limited to chemotherapy, immunotherapy, target therapy, biological therapy (tumor vaccines, cytokines, or growth factors). (13) Patients who had received or planned to receive live attenuated vaccine within 28 days before the study. (14) A history of receiving NMPA-approved drug of Chinese patent medicines with anti-tumor-related functions and indications (including Compound Banthari Capsules, Kangai Injection, Kanglaite Capsules/Injections, Aidi Injections, Brucei Oil Injections/capsules, Xiaoaiping tablets/injections, cinobufacini capsules, etc.) or Chinese herbal medicines for the purpose of anti-tumor within 14 days before the study. (15) Any active infection requiring systemic therapy by intravenous infusion of ant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival;Overall survival;Disease control rate; | — |
Countries
China
Contacts
Public ContactHongyu Zhang
The Fifth Affiliated Hospital of Sun Yat-sen University
Outcome results
None listed