colorectal cancer
Conditions
Interventions
experimental group:Donafenib + Toripalimab
Sponsors
Sichuan Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1.Subjects must volunteer to participate in the study, signed informed consent, and were able to comply with the program requirements of visits and related procedures; 2.Aged 18 to 75 years old, both men and women; 3.All subjects must have unresectable, advanced or metastatic colorectal adenocarcinoma confirmed by histologically; 4.Non-MSI-H/pMMR mCRC, immunohistochemistry or polymerase chain reaction can be used; 5.Patients with advanced or metastatic colorectal cancer who had previously received standard regimens for treatment failure (including disease progression and unacceptable adverse reactions) and were assessed for disease progression during treatment or within 3 months after the last treatment; 6.Chemotherapy regimens must include fluorouracil (5-fluorouracil/capecitabine /S-1), oxaliplatin and irinotecan; 7.Patients using oxaliplatin in adjuvant therapy should develop disease progression during adjuvant therapy or within 6 months after the completion of adjuvant therapy, and patients who progress more than 6 months after the completion of adjuvant therapy containing oxaliplatin must have undergone a subsequent oxaliplatin based chemotherapy failure before they can participate in the study; 8.Patients may have previously received bevacizumab and/or cetuximab/panitumab; 9.Have at least one evaluable lesion (RECIST 1.1 criteria); 10.Expected survival: >=3 months; 11.Eastern cooperative oncology group (ECOG) performance status score of 0 or 1; 12.More than 4 weeks elapsed between the end of the previous radiotherapy or surgery; 13.Subjects could collaborate to observe AE and efficiency; 14.The functions of important organs must meet the following requirements(no blood transfusion or G-CSF used within 14 days prior to screening): (1)Hemoglobin>=90g/L; (2)Neutrophil count>=1.5x10^9/L; (3)Platelet count>=75x10^9/L; 15.Liver function(No albumin was used during the 14 days prior to screening): (1)Serum albumin>=28g/L; (2)Total bilirubin (TBI)<=1.5x upper limit of normal (ULN); (3)Alanine aminotransferase (ALT)<=3xULN, ff there is liver metastasis aspartate aminotransferase (AST), alanine aminotransferase (ALT) <=5 ULN; 16.Renal function: (1)Serum creatinine<=1.5 ULN; 17.Coagulation function: (1)Subjects not receiving anticoagulation therapy: international normalized ratio (INR) or prothrombin time (PT) <= 1.5xULN; (2)Activated partial thromboplastin time (APTT) <= 1.5 ULN.
Exclusion criteria
Exclusion criteria: 1.Any active malignancy <= 5 years before randomization except for the specific cancer under investigation in this study and any cured limited tumors (eg, carcinoma in situ of the cervix or prostate, basal cell skin cancer); 2.Congenital or acquired immunodeficiency; 3.Existence of any active autoimmune disease or with a history of autoimmune disease (as the following examples, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary, vasculitis, nephritis, hyperthyroidism; subjects with vitiligo; in childhood asthma has been completely alleviated, adults without any intervention can be included; asthma with medical intervention could not be included); 4.History of serious mental illness; 5.Suffering from diseases that affect the absorption, distribution, metabolism or elimination of the study drugs (such as severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc); 6.Major surgery was performed within 4 weeks before the start of the study or expected to be required during the study treatment; 7.Previous stem cell allotransplantation or solid organ transplantation; 8.Have received previous targeted drug therapy such as regofinib or anti-PD-1, anti-PD-L1, anti-CTLA-4 and other immune checkpoint inhibitors; 9.Patients who have received other systemic anti-tumor therapies, including traditional Chinese medicine with anti-tumor indications, less than 2 weeks after the completion of treatment to the medication in this study, or whose adverse events caused by preoperative treatment have not recovered to <=CTCAE level 1,the toxicity of previous anticancer treatments did not include grade 1/2 neurotoxicity due to alopecia and oxaliplatin; 10.Systemic immunosuppressive therapy was used within 2 weeks prior to enrolment or was required during the study period, except in the following circumstances: (1)Intranasal, inhaled, topical or local injection (e.g. intraarticular) of corticosteroids; (2)Systemic corticosteroids at doses not exceeding 10 mg/ day of prednisone or other equivalent effects; (3)The prophylactic use of corticosteroids for hypersensitivity; 11.Concurrent administration of drugs that may prolong QTC and/or induce tip torsional ventricular tachycardia (Tdp) or affect drug metabolism; 12.A history of allergy to monoclonal antibody drugs or antiangiogenic targeted drugs; 13.Uncontrollable hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion or pericardial effusion; 14.Have active bleeding or abnormal coagulation function, have bleeding tendency or are receiving thrombolytic, anticoagulant or antiplatelet therapy; 15.A history of gastrointestinal bleeding in the past 4 weeks or a definite tendency for gastrointestinal bleeding (e.g., known local active ulcer lesions, fecal occult blood ++ or above), or other conditions that may cause gastrointestinal bleeding as determined by the investigator (e.g., severe fundus/esophageal varices), or patients with unhealed wounds, enterostomy or gastrointestinal ulceration before randomization; 16.Gastrointestinal perforation, abdominal fistula or abdominal abscess in the previous 6 months; 17.Had thrombosis or thromboembolism events in the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc; 18.Cardiovascular disease of significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable
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 ContactChen Yongchang
Sichuan Cancer Hospital
Outcome results
None listed