TriComB

5-Fluorouracil or capecitabine plus bevacizumab are recommended by major international guidelines as first-line treatment for metastatic colorectal cancer (mCRC) patients unfit for irinotecan or oxaliplatin-based chemotherapy. Trifluridine/tipiracil is approved in chemorefractory mCRC patients and combination with bevacizumab have been evaluated with promising activity results and manageable safety profile. A synergistic effect of the sequential combination of capecitabine and trifluridine/tipiracil has been demonstrated in in vitro and in vivo models and the combination of fluoropyrimidines (5-FU) and thymidine analogs (AZT) has already been evaluated in mCRC patients with initial promising results and with an acceptable safety profile. Based on these considerations we designed the present phase I/II study of trifluridine/tipiracil plus capecitabine and bevacizumab.

– mCRC patients not previously treated with chemotherapy for metastatic disease and not eligible for a chemotherapy doublet or triplet (oxaliplatin and/or irinotecan-based combination) according to investigators’ judgment;
– previous adjuvant fluoropyrimidine-based chemotherapy allowed only if more than 12 months elapsed between the end of adjuvant and first relapse;
– adequate hematopoietic, liver and renal function.

The aim is to determine the safety and recommended dose of trifluridine/tipiracil plus capecitabine and bevacizumab combination (part 1, dose escalation phase) and to assess its activity (ORR) in previously untreated mCRC patients who are deemed not eligible for intensive chemotherapy (part 2, expansion phase).