NCT04776655

Study in mCRC Patients RAS/BRAF wt Tissue and RAS Mutated LIquid BIopsy to Compare FOLFIRI Plus CetuxiMAb or BevacizumaB

Phase III Study in mCRC Patients With RAS/BRAF Wild Type Tissue and RAS Mutated in LIquid BIopsy to Compare in First-line Therapy FOLFIRI Plus CetuxiMAb or BevacizumaB (LIBImAb Study)

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 280 (estimated)
• Sponsor: Azienda USL Reggio Emilia - IRCCS · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study is a prospective, randomized phase III, to evaluate if in patients with mCRC RAS/BRAF wild type on tumor tissue and RAS mutations on liquid biopsy, treating in first line with antibody anti-VEGF (bevacizumab) plus chemotherapy (FOLFIRI) is superior in terms of PFS compared to standard treatment with antibody anti-EGFR (cetuximab) plus FOLFIRI, and then in patients RAS/BRAF wild type on tumor tissue who develop RAS mutations on liquid biopsy after the beginning of the first line treatment with cetuximab plus FOLFIRI, in the absence of a clinical or radiological progression disease, to anticipate a change of treatment with bevacizumab plus FOLFIRI further impacts on the PFS.

Detailed description

In this prospective, randomized phase III study, first of all we aim to evaluate if in patients with mCRC RAS/BRAF wild type on tumor tissue and RAS mutations on liquid biopsy, treating in first line with antibody anti-VEGF (bevacizumab) plus chemotherapy (FOLFIRI) is superior in terms of PFS compared to standard treatment with antibody anti-EGFR (cetuximab) plus FOLFIRI, and then in patients RAS/BRAF wild type on tumor tissue who develop RAS mutations on liquid biopsy after the beginning of the first line treatment with cetuximab plus FOLFIRI, in the absence of a clinical or radiological progression disease, to anticipate a change of treatment with bevacizumab plus FOLFIRI further impacts on the PFS. Patients RAS mut at first liquid biopsy will be randomized with a 1:1 ratio, to receive FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab. Patients with RAS wt at first biopsy will be treated with FOLFIRI plus cetuximab up to 8 cycles outside the protocol. Patients not progressed after 4 months (8 cycles of treatment) will undergo to a second liquid biopsy. In case of mutation of RAS, the patients will be randomized with a 1:1 ratio to continue cetuximab or to switch to bevacizumab. The treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, other conditions compromise subject safety or patient refusal. Plasma samples will be analyzed for mutations of KRAS, NRAS and in BRAF V600 using the Idylla system (Biocartis). Samples will be retrospectively analysed by next generation sequencing using the Oncomine Pan-Cancer Cell-free Assay, which assesses genetic alterations in 52 driver genes, in order to evaluate the possible correlation of tumor heterogeneity with patients' outcome. With this study we could identify the best monoclonal antibody treatment in mCRC RAS/BRAF wild type on tumor tissue and RAS mutated on liquid biopsy and if liquid biopsy can be used in clinical practice as an integrated analysis to mutational tissue evaluation, to identify RAS mutations not detected on tissue.

Conditions

• Colorectal Cancer
• Metastatic Colorectal Cancer
• RAS Mutation

Interventions

Type	Name	Description
DRUG	Bevacizumab	This is the treatment assigned to experimental arm: All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn.
DRUG	Cetuximab	This is the treatment assigned to control arm: All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn.
DRUG	5-FU	FOLFIRI regimen: This is the treatment assigned to control and to experimental arms: All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn.
DRUG	Irinotecan	FOLFIRI regimen: This is the treatment assigned to control and to experimental arms: All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn.
DRUG	Calcium levofolinate	FOLFIRI regimen: This is the treatment assigned to control and to experimental arms: All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn.

Timeline

• Start date: 2021-04-30
• Primary completion: 2025-05-04
• Completion: 2026-05-04
• First posted: 2021-03-02
• Last updated: 2025-10-02

Locations

4 sites across 1 country: Italy