Irinotecan, TAS-102 Plus Bevacizumab as a Second-Line Therapy in mCRC Patients

Metastatic Colorectal Cancer Clinical Trial

Official title: 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)

Status Recruiting

Clinical Trial Summary

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.

Clinical Trial Description

This was a single-arm, open-label, phase I, dose-escalation study to establish the recommended phase II dose (RP2D) for the combination of TAS-102, irinotecan, and bevacizumab and evaluate its safety.

This study followed a classic 3+3 design, in which patients received escalating doses of TAS-102 (20, 25, 30, or 35 mg/m2/dose, administered twice daily for days 1-5) and irinotecan (135, 150, 165, or 180 mg/m2 on day 1) with a fixed dose of bevacizumab (5 mg/kg on day 1), repeated every 14 days. Initially, three patients will receive therapy at dose level 1. If dose-limiting toxicity (DLT) occurred, an additional three patients were enrolled at the same dose level. If none of the first three patients or less than two of the six patients exhibited DLT, then the study regimen was escalated to a higher dose level. If two or more DLTs occurred, the study regimen was reduced to a lower dose level.

The maximum tolerated dose (MTD) was defined as the highest dose level at which less than one-third of evaluable patients treated had a DLT during the first or second cycle of drug administration. The RP2D was defined as the MTD. At least six patients at the MTD or RP2D were needed to estimate these doses accurately.

Treatment was continued until RECIST-defined disease progression or clinical disease progression, unacceptable toxicity, patient request to withdraw treatment, and a treatment-free period of >30 consecutive days.

Adverse events (AEs) were graded based on the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.

The response was assessed by the investigator according to RECIST version 1.1. ;

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

• NCT number: NCT06202001
• Study type: Interventional
• Source: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Contact: Yongkun Sun
• Phone: +8613141276041
• Email: hsunyk@126.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 1, 2022
• Completion date: September 30, 2026