The goal of this clinical trial is to demonstrate the non-inferiority of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of progression free survival in patients with refractory metastatic colorectal cancer(mCRC) patients. It will also try to estimate the effect of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of OS, ORR, and DCR in patients with refractory mCRC. Other secondary objectives are to compare the safety and tolerance, and the impact on QoL of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in patients with refractory mCRC.
Sign Informed Consent Form (ICF) must be obtained during the screening visit, prior to the performance of any study procedure；
Male or female patient aged ≥18 years old;
Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all other histological types are excluded);
RAS status must have been previously determined (mutant or wild-type) based on local assessment of tumor biopsy;
Prior trifluridine/tipiracil or TKI regimens for the treatment of advanced colorectal cancer;
Pregnancy, lactating female or possibility of becoming pregnant during the study;
Patients currently receiving or having received anticancer therapies within 4 weeks prior to randomization;
Has not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to randomization (excluding alopecia, and skin pigmentation);
Parallel
Trifluridine/Tipiracil + Regorafenib
DrugTrifluridine/tipiracil will be administered orally BID at a starting dose of 30 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Regorafenib will be administered orally QD at a dose-escalation strategy (80 mg/day, followed by weekly increase of 40 mg to 120 mg/day), if no significant drug-related adverse events occurred and 120 mg/day for 21 days of a 28-day cycle.
Trifluridine/tipiracil + bevacizumab
DrugTrifluridine/tipiracil will be administered orally BID at a starting dose of 35 mg per square meter of body-surface area, on days 1 through 5 every 2 weeks. Bevacizumab, at a dose of 5 mg per kilogram of body weight, will be administered IV every 2 weeks (day 1 and day 15).
Progression free survival
The primary objective is to demonstrate the non-inferiority of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of PFS in patients with refractory mCRC
Overall survival (OS)
To estimate the effect of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of OS in patients with refractory mCRC.
Objective Response Rate（ORR）
To estimate the effect of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of ORR in patients with refractory mCRC.
Disease Control Rate（DCR）
To estimate the effect of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in terms of DCR in patients with refractory mCRC.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
To compare the safety of trifluridine/tipiracil + regorafenib vs trifluridine/tipiracil + bevacizumab in patients with refractory mCRC.
Click on the lead sponsor to view all of their trials.
