Phase I/II Study of Irinotecan Plus Trifluridine/Tipiracil (TAS-102) in Combination With Bevacizumab as a Second-Line Therapy for Patients With Metastatic Colorectal Cancer (mCRC)
In mCRC, response to second-line chemotherapy is limited, and few treatment options are available. It is urgent to design an optimal second-line treatment regimen to improve the response rate and prolong the survival of patients with mCRC. Several studies preliminarily demonstrated that irinotecan, TAS-102 plus bevacizumab regimen could bring promising efficacy with a tolerable safety profile for patients with mCRC as a second-line treatment. This phase I/II study was aimed to determine the recommended phase II dose (RP2D) of the combination of TAS-102, irinotecan, and bevacizumab for future clinical trials in patients with mCRC refractory to both fluoropyrimidine and oxaliplatin and to evaluate its safety and preliminary efficacy.
• Colorectal adenocarcinoma confirmed histologically or histopathologically.
• Patients were clinically diagnosed with metastatic colorectal cancer based on computed tomography (CT) scan and magnetic resonance imaging (MRI) according to AJCC 8th edition.
• Patients have received oxaliplatin-based first-line chemotherapy with or without targeted therapy, immunotherapy or radiotherapy.
• Age ≥18 and ≤70.
• ECOG physical status score is 0 or 1, and no obvious deterioration within 2 weeks prior to use on Day 1 of Cycle 1.
• Appropriate organ function according to the following laboratory test values:
‣ Hemoglobin value ≥90g/L.
⁃ White blood cell count ≥3.5\*109/L.
⁃ Absolute neutrophil count ≥1.5\*109/L.
⁃ Platelet count ≥100\*109/L.
⁃ Serum creatinine ≤ upper limit of normal (ULN) or creatinine clearance ≥60ml/min.
⁃ Total serum bilirubin ≤1.5\* upper normal limit (ULN).
⁃ Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤2.5\* upper limit of normal value (ULN).
• Signed the informed consent.