医学
伊立替康
胰腺癌
内科学
养生
吉西他滨
结直肠癌
联合疗法
肿瘤科
癌症
临床研究阶段
胃肠病学
腺癌
核苷类似物
临床试验
核苷
化学
立体化学
作者
Olatunji B. Alese,Walid L. Shaib,Mehmet Akce,Christina Wu,Bassel F. El‐Rayes
标识
DOI:10.1200/jco.2018.36.15_suppl.tps4155
摘要
TPS4155 Background: Trifluridine/tipiracil (FTD/TPI, also known as TAS-102) is a combination of a nucleoside analogue and a thymidine phosphorylase inhibitor. TAS-102 has shown activity in 5FU-resistant colorectal cancer (CRC). Nano liposomal-Irinotecan (Nal-IRI) achieve higher intra-tumor concentrations than irinotecan (142-fold) and its major metabolite, SN-38 (9-fold), resulting in superior anti-tumor activity compared to free irinotecan in multiple tumor xenografts. Clinical trials have established activity of Nal-IRI combined with 5FU in pancreatic cancer. The combination of Nal-IRI with the more potent nucleoside analogue TAS-102 may result in a more effective systemic therapy regimen in CRC and pancreatic cancer. The aim of this study is to define the recommended phase II dose (RP2D) of the combination and evaluate the activity in pancreatic cancer and CRC. Methods: Eligible patients for the phase I trial include stage IV or locally advanced unresectable gastrointestinal adenocarcinomas, who have failed at least one prior therapy; age ≥18 years, ECOG PS 0-1 and measurable disease per RECIST 1.1. The trial design is standard 3+3. TAS-102 is administered orally in four dose levels of 25, 25, 30, 35mg/m2 BID on days 1-5, with Nal-IRI at corresponding dose levels of 50, 70, 70, 70mg/m2 IV on day 1 , in 14-day cycles. After recommended phase II doses are established, an expansion phase will enroll 20 patients with pancreatic adenocarcinoma (Arm A) and 20 patients with colorectal adenocarcinoma (Arm B). These patients must have either locally advanced unresectable or metastatic disease, and have failed at least one prior therapy that must not have included irinotecan. The primary endpoint of the phase II portion is overall response rate. Simon's two-stage design will be used for each arm of the phase II component. In the first stage, 10 patients will be accrued. If there are fewer than 1 responder, the cohort will be stopped. Otherwise, 10 additional patients will be accrued for a total of 20. Enrollment to the escalation phase I part of the study started in February 2018. Clinical trial information: NCT03368963.
科研通智能强力驱动
Strongly Powered by AbleSci AI