Trifluridine/Tipiracil Combined With Cetuximab in the Treatment of Third-line and Above RAS/BRAF Wild-type Metastatic Colorectal Cancer: A Single-center, Prospective Phase Ib/II Study

IRB-2023-1072

This study is a single-center, prospective, single-arm exploratory study aimed at evaluating the efficacy and safety of trifluridine/tipiracil in combination with cetuximab in the treatment of third-line and above RAS/BRAF wild-type metastatic colorectal cancer.

2024-04-01

2025-03-01

2025-12-01

Recruiting

Early phase I

26

Inclusion Criteria: 1. Patient able and willing to provide written informed consent and to comply with the study protocol and follow-up inspection. 2. Histologically or cytologically confirmed metastatic adenocarcinoma of the colon; excluding appendiceal and anal canal cancers. 3. Previously received at least second-line treatment, including two standard treatment regimens (such as fluoropyrimidine, capecitabine, irinotecan, oxaliplatin with or without anti-VEGF or anti-EGFR agents), if previously received first-line anti-EGFR therapy, achieving at least a partial response (PR) or above, with a discontinuation interval of at least one year. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. 5. Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) (based on RECIST 1.1 criteria, with the longest diameter of tumor lesions on CT/MRI scan ≥10mm, and the shortest diameter of lymph node lesions on CT/MRI scan ≥15mm). 6. Wild-type RAS/BRAF gene detected. 7. Able to take oral medication. 8. Normal organ function, meeting the following criteria within 14 days before treatment initiation: * Neutrophil count ≥1.5×10\^9/L; * Platelet count ≥75×10\^9/L; * Hemoglobin ≥9.0g/dL; * Aspartate aminotransferase (AST) ≤2.5×upper limit of normal (ULN) (or ≤5×ULN if liver metastases); * Alanine aminotransferase (ALT) ≤2.5×ULN (or ≤5×ULN if liver metastases); * Total bilirubin ≤1.5×ULN; * Creatinine clearance (calculated by Cockcroft and Gault formula) \>60mL/min or serum creatinine ≤1.5×ULN; 9. Expected survival time \>3 months (90 days). 10. Women of childbearing potential must have used reliable contraception for 7 days prior to enrollment, have had a negative pregnancy test, and agree to use appropriate contraception methods during the trial and for 6 months after the last dose of investigational drug. Men must agree to use appropriate contraception methods or have undergone surgical sterilization during the trial and for 6 months after the last dose of investigational drug. Exclusion Criteria: 1. Prior treatment with Trifluridine/Tipiracil; 2. Patients with known dMMR or MSI-H advanced colorectal cancer who have not previously received anti-PD-1 or PD-L1 inhibitors; 3. Participation in another drug clinical trial or receipt of systemic chemotherapy, radiotherapy, or biologic therapy within the past 4 weeks; 4. Known or suspected brain metastases; 5. Synchronous or metachronous cancer with a disease-free survival of ≥5 years (except for colorectal cancer) excluding cured or curatively treated mucosal cancers (esophageal cancer, gastric cancer, cervical cancer, non-melanoma skin cancer, bladder cancer, etc.); 6. Factors significantly affecting oral drug absorption, such as dysphagia, chronic diarrhea, and gastrointestinal obstruction; uncontrolled Crohn's disease or ulcerative colitis; 7. Symptomatic malignant effusion requiring symptomatic treatment (including pleural effusion, ascites, pericardial effusion); 8. Pregnant or lactating women; patients with reproductive potential unwilling or unable to use effective contraceptive measures; 9. Known allergy to the investigational drug, drug class, or its components; 10. Requirement for systemic corticosteroid therapy (excluding local steroids and cetuximab pre-treatment); 11. History of interstitial lung disease (interstitial pneumonia, pulmonary fibrosis, etc.) or radiographic evidence of interstitial lung disease; 12. Active local or systemic infections requiring treatment; 13. New York Heart Association (NYHA) functional classification ≥II or severe heart disease; 14. Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) or history of active hepatitis B or hepatitis C; 15. Unresolved toxicity (CTCAE\>Grade 1) or incomplete recovery from previous cancer surgery. 16. Patients deemed unsuitable for the study by the investigator.

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2024-04-23