Observational Study Regarding the Combination of Fluoropyrimidine and Bevacizumab in Patients With mCRC (FLOWER)

March 25, 2026 updated by: Salvatore Lisa, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Multicenter Observational Study Regarding the Combination of Fluoropyrimidine and Bevacizumab in the Treatment of Patients With Metastatic Colorectal Cancer

This study will enroll patients with metastatic colorectal cancer treated with the combination of Trifluridine/Tipiracile and Bevacizumab across 15 italian centers.

Study Overview

Status

Active, not recruiting

Conditions

Colon Cancer Metastatic

Intervention / Treatment

Drug: Fluoropyrimidine

Detailed Description

The FLOWER study is a multicenter, observational investigation evaluating the real-world effectiveness and safety of a therapeutic combination of fluoropyrimidines and bevacizumab in patients with metastatic colorectal cancer (mCRC).

Colorectal cancer remains one of the most common and lethal cancers in Italy, and although early screening has improved detection rates, a substantial proportion of patients still present with or eventually develop metastatic disease. For those whose tumors do not exhibit specific molecular characteristics (such as dMMR or MSI-high), standard first- and second-line treatments often involve chemotherapy regimens based on fluoropyrimidines combined with agents like oxaliplatin or irinotecan, alongside targeted therapies such as bevacizumab or, in RAS wild-type tumors, anti-EGFR drugs.

However, once patients become refractory to these initial therapies, treatment options become more limited. While some benefit from newer targeted approaches like the combination of cetuximab and encorafenib in BRAF-mutated cancers, many patients without actionable mutations rely on drugs like regorafenib or trifluridine-tipiracil, which have shown only modest benefits. Recent evidence from the SUNLIGHT trial has shown that adding bevacizumab to TAS-102 significantly improves survival in this setting, highlighting the potential benefit of combining antiangiogenic agents with chemotherapy even in heavily pretreated patients. Building on this rationale, the FLOWER study aims to assess how effective and safe the combination of fluoropyrimidines and bevacizumab is when used in daily clinical practice.

The primary objective of the study is to evaluate overall survival, while secondary endpoints include progression-free survival, response rates, safety, and identification of clinical or molecular factors that may predict outcomes. The study will include approximately 300 patients treated between 2023 and 2026. Both retrospective and prospective data will be collected, and no additional procedures, exams, or financial costs are imposed on the healthcare system. The study follows ethical guidelines laid out by the Declaration of Helsinki and has been approved by the regional ethics committee.

Study Type

Observational

Enrollment (Estimated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Italy
- Lazio
  - Rome, Lazio, Italy, 00160
    - Policlinico Universitario Agostino Gemelli

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

Sampling Method

Probability Sample

Study Population

Patients with metastatic colorectal cancer treated with fluoropyrimidines and bevacizumab.

Description

Inclusion Criteria:

Age ≥18 years;
ECOG PS 0-2;
Histologic diagnosis of colorectal cancer;
Treatment with fluoropyrimidine plus bevacizumab.

Exclusion Criteria:

ECOG PS ≥3;
Absence of histologic diagnosis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival Time Frame: up to 30 months from the date of treatments' start	Time from start of the treatment to death from any cause up to 30 months from the date of treatments' start.	up to 30 months from the date of treatments' start
Progression-free survival Time Frame: up to 30 months from the date of treatments' start	time from the start of the treatment to disease progression or death from any cause, whichever occurred first, up to 30 months from the date of treatments' start.	up to 30 months from the date of treatments' start

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

Principal Investigator: Lisa Salvatore, Fondazione Policlinico Universitario A. gemelli, IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 1, 2025

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

August 1, 2027

Study Registration Dates

First Submitted

July 17, 2025

First Submitted That Met QC Criteria

March 25, 2026

First Posted (Actual)

March 27, 2026

Study Record Updates

Last Update Posted (Actual)