Genotype-driven Phase I Study of Weekly Irinotecan Liposomes in Combination With Capecitabine-based Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer
This study is a multicenter, open, and phase I dose increasing clinical study. Based on the UGT1A1 \* 28 and \* 6 genotypes of patients with locally advanced rectal cancer, determine the dose limiting toxicity (DLT) and maximum tolerable dose (MTD) of weekly irinotecan liposomes in concurrent chemoradiotherapy with capecitabine, investigate the tolerance of irinotecan liposome combined with capecitabine in concurrent chemoradiotherapy with locally advanced rectal cancer, and recommend the dosage for Phase II clinical study，and explore the pharmacokinetic characteristics of irinotecan liposomes combined with capecitabine.At the same time，Preliminary observe the efficacy and safety of irinotecan liposomes combined with capecitabine in chemoradiotherapy.The study plans to recruit 30 patients with advanced rectal cancer who have not received any therapy.
• Diagnosed as rectal adenocarcinoma by histopathology, immunohistochemical pMMR or MSI-L, MSS;
• The baseline clinical stage is T2-4 and/or N+, which is not suitable for initial local resection to achieve curative effect;
• The distance between the tumor and the anus is\<=10cm;
• No distant metastasis;
• Age range from 18 to 70 years old, regardless of gender;
• ECOG PS score 0-1 points;
• The UGT1A1 \* 6 and UGT1A1 \* 28 gene phenotypes are all wild-type (GG+6/6), unit point mutant (GG+6/7 or GA+6/6), and dual site mutant (GG+7/7 or AA+6/6 or GA+6/7);
• Not receiving chemotherapy or any other anti-tumor treatment before enrollment;
• Able to comply with the protocol during the research period;
⁃ Sign written informed consent.