Late stage colorectal cancer patients with RAS mutations
Conditions
Interventions
1 groups:Participants in this study will receive Torametinib in combination with FOLFIRI/FOLFOX chemotherapy, with or without Bevacizumab. If the patient has previously received FOLFOX as first-line c
Sponsors
Tianjin People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18-75 years (inclusive), both male and female are eligible. 2. ECOG performance status of 0-1. 3. Patients with histologically or cytologically confirmed advanced colorectal cancer. 4. Previous genetic testing results show RAS mutation positivity. 5. According to RECIST v1.1 assessment, there is at least one measurable lesion. 6. Have received first-line standard chemotherapy regimen, and radiological evidence shows disease progression; for neoadjuvant or adjuvant therapy (chemotherapy or chemoradiotherapy), if disease progression occurs during treatment or within 6 months after cessation of treatment, it should be considered as first-line treatment (investigator's assessment according to RECIST 1.1); or patients intolerant to standard treatment regimens. 7. Expected survival of >3 months. 8. Normal function of major organs and bone marrow, meeting the following requirements: - Blood routine: Hemoglobin >=100 g/L (no blood transfusion within 14 days); absolute neutrophil count >=1.5×10?/L; platelet count >=100×10?/L. - Liver function: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) =30 g/L. - Renal function: Serum creatinine 60 mL/minute. - Cardiac function: Echocardiographic left ventricular ejection fraction (LVEF) >=55%; electrocardiogram QTcF =2+, a 24-hour urine protein quantification test should be performed, if the quantification test =1g/24 h urine protein quantification cannot be enrolled; patients with urine protein >=2+ who have not undergone quantitative testing cannot be enrolled. 9. Able to take oral medication. 10. Women of childbearing age must have a negative pregnancy test (serum or urine) within 14 days before enrollment and voluntarily agree to use appropriate contraception during the observation period and for 6 months after the last administration of the study drug; for men, they should be surgically sterilized or agree to use appropriate contraception during the observation period and for 6 months after the last administration of the study drug. 11. Willing to participate and sign the informed consent form, with good expected compliance and able to cooperate with the study according to the protocol requirements.
Exclusion criteria
Exclusion criteria: 1. Known contraindications that affect the investigator's choice of therapeutic drug use (in accordance with the latest drug insert). 2. Underwent major surgery (biopsy or minor outpatient surgery, such as vascular access placement, is excluded) or experienced severe trauma within 4 weeks before the first drug administration. 3. Presence of clinically symptomatic, uncontrollable third-space effusions (e.g., large pleural effusion or ascites) that cannot be controlled by drainage or other means. 4. Symptomatic or untreated brain metastases, leptomeningeal metastases, or spinal cord compression in subjects, with the following exceptions: asymptomatic brain metastasis subjects (i.e., no progressive central nervous system symptoms caused by brain metastases, no need for corticosteroids or antiepileptic drugs, and stable lesions confirmed by imaging for >=4 weeks; for patients who have received stereotactic radiosurgery or surgical treatment for brain metastases, if there is no disease progression in the brain for a period of >=3 months, they are eligible for inclusion). 5. Impaired cardiac function or clinically significant cardiovascular and cerebrovascular diseases, including any of the following: - Acute coronary syndrome (including acute myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, and stent implantation) within 6 months before the start of treatment. - Symptomatic congestive heart failure (New York Heart Association [NYHA] class >=II); evidence of clinically significant arrhythmias and/or conduction abnormalities within 6 months before the start of treatment or currently. - Poorly controlled hypertension (systolic blood pressure >=150 and/or diastolic blood pressure >=100 mmHg under medication). - Echocardiographic evidence of valvular heart disease (>=grade 2). Note: Patients with grade 1 valvular heart disease (e.g., mild regurgitation/stenosis) are allowed to be enrolled, but patients with moderate valvular thickening are excluded. - History of congenital long QT syndrome; or taking drugs known to prolong the QT interval and unable to discontinue during the study period. 6. History of retinal disease at baseline or during screening, such as retinal vein occlusion (RVO), retinal artery occlusion, retinal vasculitis, diabetic retinopathy, hypertensive retinopathy, retinal capillary hemangioma (Costs disease), retinal pigment epithelial detachment (RPED), etc.; presence of risk factors for RVO during screening (e.g., uncontrolled glaucoma or high intraocular pressure, history of hyper-viscosity or hypercoagulable syndrome); RPED and other retinal diseases. 7. Interstitial lung disease or interstitial pneumonia, including clinically significant radiation pneumonitis (i.e., affecting activities of daily living or requiring intervention). 8. Positive for human immunodeficiency virus (HIV) antibodies, positive for syphilis antibodies (Anti-TP), positive for hepatitis C virus (HCV) antibodies and positive for HCV RNA, positive for hepatitis B surface antigen (HBsAg) and positive for HBV DNA (HBsAg-positive patients require further HBV DNA testing, HBV DNA >=200 IU/ml, or >=10^3 copies/ml). 9. History of chronic inflammatory bowel disease or Crohn's disease requiring medical intervention (immunomodulators or surgery) within 12 months before the start of treatment. 10. Known history of acute or chronic pancreatitis within 6 months before the start of study treatment. 11. Active gastrointestina
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assessing the safety of Torametinib in combination with FOLFIRI/FOLFOX and Bevacizumab in patients with RAS-mutated advanced colorectal cancer.; | — |
Secondary
| Measure | Time frame |
|---|---|
| objective response rate;Progression-free survival, PFS;disease control rate;Overall survival,OS; | — |
Countries
China
Contacts
Public ContactYan Hao
Tianjin People's Hospital
Outcome results
None listed