Colorectal cancer
Conditions
Interventions
experiment group:tunlametinib, vemurafenib and cetuximab
Sponsors
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1) 18-75 years old (inclusive), male or female; 2) ECOG score of 0-1; 3) Patients with histologically or cytologically confirmed unresectable stage III or metastatic stage IV CRC; 4) Previous genetic testing results showed positive BRAF V600E mutation; 5) at least one measurable lesion as assessed by RECISTv1.1; 6) Subjects who have not received prior systemic first-line therapy (Note: Subjects who have received chemotherapy in the early stage of the disease, stage I-III, and perioperative will be considered to have received 1 line of systemic therapy in the metastatic disease stage if they have new lesions or evidence of disease recurrence during treatment or within 6 months after the last chemotherapy administration) but the following conditions can also be considered: Neoadjuvant, adjuvant therapy for more than 6 months; Received only one chemotherapy session; 7) Expected survival > 6 months; 8) The function of major organs and bone marrow is normal, and the following requirements are met: • Complete blood count: hemoglobin > = 90 g/L (no transfusion within 14 days); Absolute neutrophil count> = 1.5×10^9/L; Platelet count > = 75×10^9/L; • Liver function: alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) = 30 g/L; • Renal function: serum creatinine clearance calculated by ULN or Cockroft-Gault formula; • Cardiac function: left ventricular ejection fraction (LVEF) > = 55% on echocardiography; ECG QTcF< = 480ms; Creatine kinase (CK) < = 1× ULN, troponin/hypersensitivity troponin < = 1×ULN; • Coagulation function: International normalized ratio (INR) of prothrombin time < = 1.5×ULN; Activated partial thromboplastin time (APTT) < = 1.5×ULN; 9) Able to administer oral medication; 10) Women of childbearing potential must have a negative pregnancy test (serum or urine) result within 14 days prior to enrollment and voluntarily use an adequate method of contraception during the observation period and for 3 months after the last administration of study drug; For males, should be surgically sterile or agree to use an appropriate method of contraception during the observation period and for 3 months after the last administration of study drug; 11) Voluntarily participate in and sign the informed consent form, and it is expected that the compliance will be good and be able to cooperate with the study according to the requirements of the protocol.
Exclusion criteria
Exclusion criteria: 1) Known contraindications that affect the investigator's choice of therapeutic drug use (in accordance with the latest drug instructions); 2) Prior receipt of MEK inhibitors, BRAF inhibitors, EGFR monoclonal antibodies; 3) Prior systemic anti-tumor therapy; 4) Major surgery (except biopsy, outpatient minor surgery, such as vascular access) or severe trauma within 4 weeks prior to the first dose; 5) Presence of a clinically symptomatic, uncontrollable third space effusion (such as large pleural effusion or ascites); 6) Cardiovascular and cerebrovascular diseases with impaired cardiac function or clinical significance, including but not limited to any of the following: • Acute coronary syndromes, including acute myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, and stenting, within 6 months prior to treatment initiation; • Symptomatic congestive heart failure (New York Heart Association [NYHA] classification > = Class II); Evidence of clinically significant cardiac arrhythmias and/or conduction abnormalities within 6 months prior to treatment initiation or currently; • poorly controlled hypertension (medically controlled systolic blood pressure > = 140 and/or diastolic blood pressure >= 90 mmHg); • abnormal heart valve morphology documented by echocardiography (> = grade 2), NOTE: Patients with grade 1 valvular morphological abnormalities (such as mild regurgitation/stenosis) are allowed to enroll, but patients with moderate valve thickening are not allowed to enroll; • Have a history of congenital long QT syndrome; or those who are taking medications known to prolong the QT interval and there is no guarantee of discontinuation during the study; 7) Retinal diseases in the past or at screening, such as: retinal vein occlusion (RVO), retinal artery occlusion, retinal vasculitis, diabetic retinopathy, hypertensive retinopathy, retinal telangiectasia (Costs disease), retinal pigment epithelium detachment (RPED), etc.; Risk factors for RVO at screening (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndrome); retinal diseases such as RPED; 8) Patients with interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring intervention); 9) Positive human immunodeficiency virus (HIV) antibody, syphilis antibody (Anti TP), hepatitis C virus (HCV) antibody positive and HCV RNA positive, hepatitis B virus surface antigen (HBsAg) positive and HBV DNA positive (HBsAg positive requires further HBV DNA, HBV DNA > = 200IU/ml, or >= 103 copies/ml); 10) History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulators or surgery) within 12 months prior to treatment initiation; 11) Known history of acute or chronic pancreatitis within 6 months prior to initiation of study treatment; 12) Active gastrointestinal bleeding requiring treatment; 13) History of allogeneic bone marrow transplantation or organ transplantation; 14) Presence of uncontrolled active infectious disease (e.g., requiring intravenous infusion of antibiotics, antifungal, or antiviral drugs) within 2 weeks prior to the first dose, or unexplained febrile > during screening/prior to the first dose 38.5°C; 15) Uncorrectable electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia by blood biochemical tests); 16) Previous or current neurom
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective Response Rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression Free Survival, PFS;Overall survival, OS; | — |
Countries
China
Contacts
Public ContactLiHao
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Outcome results
None listed