Colorectal CancerPhase 3LIBImAbNCT04776655

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

A Phase 3 study testing Bevacizumab, Cetuximab and 5-FU in people with Colorectal Cancer and Metastatic Colorectal Cancer, run by Azienda USL Reggio Emilia - IRCCS at 4 sites in Italy.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Colorectal Cancer, Metastatic Colorectal Cancer, RAS Mutation
What is being tested?: Bevacizumab, Cetuximab and 5-FU
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 280 participants
Where: 4 sitesItaly
Study dates: 30 Apr 2021to Dec 2026
Phase: Phase 3
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Provision of written informed consent;
Male or female > 18 years of age;
Histologically confirmed diagnosis of colorectal adenocarcinoma RAS/BRAF wild type (analysed either on primary and/or related metastasis);
Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;
Patient with left colorectal cancer;
Patients suitable for first line chemotherapy;

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Life expectancy > 3 months;
At least one site of measurable disease per RECIST criteria ver. 1.1;
ECOG Performance status = 2;
Adequate bone marrow, liver and renal function assessed before starting study treatment;
If DPD status is known it must be wild type. No restrictions are applied if DPD status in unknown;
Women of childbearing potential must have a negative blood pregnancy test within 24 hr prior to the start of study treatment. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive.
Subjects and their partners must be willing to avoid pregnancy during the trial and until 5 months for WOCBP (Women of Childbearing Potential) and 7 months for male subjects with female partners of WOCBP after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator (barriers contraceptive measure or oral contraception).

Who cannot join

Previous chemotherapy treatment, with the exception of patient treated in adjuvant setting completed at least 6 months before the randomization;
Any contraindication to the use of Cetuximab, Bevacizumab, Irinotecan, 5FU or folinic acid;
Radiotherapy to any site within 4 weeks before the randomization;
Serious, non-healing wound, ulcer, or bone fracture;
Evidence of bleeding diathesis or coagulopathy;
Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy;

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Additional malignancy in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy;
Active and untreated brain (CNS) metastases and/or carcinomatous meningitis;
Active infection requiring systemic therapy or active disseminated intravascular coagulation;
History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antobodies);
Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection;
Chronic, daily treatment with high-dose aspirin (>325 mg/day);
Any previous venous thromboembolism > NCI CTCAE Grade 3;
History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment. History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea;
Current, recent (within 10 days prior to study treatment start) or ongoing treatment with anticoagulants for therapeutic purposes;
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study;
History of any severe hypersensitivity reactions to any monoclonal antibody;
A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study

Trial locations and contacts

4 sites in 1 country.

Italy4 sites

Ospedale San Salvatore
Coppito, L'Aquila, 67100
Ospedale Civile di Guastalla
Guastalla, Reggio Emilia, 42016
Azienda ULSS 3 Serenissima
Mirano, VE, 30035
AUSL/IRCCS di Reggio Emilia
Reggio Emilia, Reggio Emilia, 42123

Other trials in Italy

About this study

Official title: 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)

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.

Read the 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
Being tested: Bevacizumab, Cetuximab, 5-FU, Irinotecan, Calcium levofolinate
Keywords: mCRC, liquid biopsy, RAS
Medical subject headings: Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BevacizumabDrug
Also called Avastin
This is the treatment assigned to experimental arm:
All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn.
CetuximabDrug
Also called Erbitux
This is the treatment assigned to control arm:
All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn.
5-FUDrug
Also called 5 Fluorouracil
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.
IrinotecanDrug
Also called Irinotecano
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.
Calcium levofolinateDrug
Also called Levofolinic acid
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.

Study groups in NCT04776655
Study group	Role	What they receive
Bevacizumab in combination with FOLFIRI chemotherapy	Experimental	Bevacizumab will be administrered at a dose of 5 mg/kg iv every 2 weeks. The first dose of Bevacizumab will be administered over 90 minutes. Then, if the first infusion is well tolerated without infusion-related reaction, the second dose will be administered over 60 minutes. Then, if the second dose is also well tolerated without an infusion reaction, all subsequent doses will be administered over 30 minutes. Dosage form: Intravenous use All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn. Receives: Drug: Bevacizumab; Drug: 5-FU; Drug: Irinotecan; Drug: Calcium levofolinate
Cetuximab in combination with FOLFIRI chemotherapy	Active comparator	Cetuximab will be administered at a dose of 500 mg/m² iv every 2 week (14 days/cycle) Dosage form: Intravenous use All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn. Receives: Drug: Cetuximab; Drug: 5-FU; Drug: Irinotecan; Drug: Calcium levofolinate

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression free survival (PFS) in patients with RASmut at liquid biopsy and RASwt on tissue.
The primary objective of the study is to assess whether the combination of bevacizumab plus chemotherapy is superior to cetuximab plus chemotherapy in terms of progression free survival (PFS) in patients with RASmut at liquid biopsy and RASwt on tissue.
Measured: From the date of randomization to the date of first progression or death for any cause, whichever occurs first, assessed up to 36 months

Secondary outcomes (5)

Overall survival (OS)
Overall survival (OS) defined as the time from start of treatment to the date of death for any cause or, for living patients, the date of last contact.
Measured: up to 36 months
Objective response rate (ORR)
Objective Response Rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR) as best response during treatment as determined by RECIST 1.1.
Measured: up to 36 months
Prevalence of RAS mutation
Percentage of RAS mut patients on the total of patients who undergone to liquid biopsy at the first and second evaluations.
Measured: up to 36 months
Patients Safety
The maximum toxicity grade experienced by each patient, for each toxicity, according to NCI-CTCAE v. 5.0; the number of patients experiencing grade 3-4 toxicity for each toxicity; type, frequency and nature of SAEs; patients with at least a SAE; patients with at least a SADR; patients with at least a SUSAR.
Measured: up to 36 months
Compliance
The compliance to treatment will be described presenting number of administered cycles; frequency and reasons for drug discontinuation and treatment modifications.
Measured: up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Apr 2021Dec 2026

First posted2 Mar 2021
Study start30 Apr 2021
Primary completion4 May 2025
Study completionDec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Colorectal CancerStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Phase III, randomized, open-label, comparative, multi-centre study
Masking: None (open label)
Enrolment: 280 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04776655
Sponsor's protocol ID: 2020-005078-82
Acronym: LIBImAb
Status last verified: Jul 2026
First submitted: 23 Feb 2021
Last updated: 24 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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)
ClinicalTrials.gov ID: NCT04776655
Acronym / sponsor ID: LIBImAb / 2020-005078-82
Conditions: Colorectal Cancer, Metastatic Colorectal Cancer, RAS Mutation
Keywords: mCRC, liquid biopsy, RAS
Phase: Phase 3
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 280 participants (estimated)
Lead sponsor: Azienda USL Reggio Emilia - IRCCSOther government
Collaborators: Istituto Di Ricerche Farmacologiche Mario Negri, Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale
Study start: 30 Apr 2021 (actual)
Primary completion: 4 May 2025 (actual)
Study completion: Dec 2026 (estimated)
First posted: 2 Mar 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Patients RAS mut at first liquid biopsy will be randomized with a 1:1 ratio, to receive FOLFIRI plus cetuximab or FOLFIRI plus bevacizumab.

The treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, other conditions compromise subject safety or patient refusal.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2
Model description: Phase III, randomized, open-label, comparative, multi-centre study

Arm	Type	Receives
Bevacizumab in combination with FOLFIRI chemotherapy	Experimental	Drug: Bevacizumab, Drug: 5-FU, Drug: Irinotecan, Drug: Calcium levofolinateBevacizumab will be administrered at a dose of 5 mg/kg iv every 2 weeks. The first dose of Bevacizumab will be administered over 90 minutes. Then, if the first infusion is well tolerated without infusion-related reaction, the second dose will be administered over 60 minutes. Then, if the second dose is also well tolerated without an infusion reaction, all subsequent doses will be administered over 30 minutes. Dosage form: Intravenous use All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn.
Cetuximab in combination with FOLFIRI chemotherapy	Active comparator	Drug: Cetuximab, Drug: 5-FU, Drug: Irinotecan, Drug: Calcium levofolinateCetuximab will be administered at a dose of 500 mg/m² iv every 2 week (14 days/cycle) Dosage form: Intravenous use All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

Provision of written informed consent;
Male or female > 18 years of age;
Histologically confirmed diagnosis of colorectal adenocarcinoma RAS/BRAF wild type (analysed either on primary and/or related metastasis);
Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease;
Patient with left colorectal cancer;

Key exclusion criteria (18 listed)

Previous chemotherapy treatment, with the exception of patient treated in adjuvant setting completed at least 6 months before the randomization;
Any contraindication to the use of Cetuximab, Bevacizumab, Irinotecan, 5FU or folinic acid;
Radiotherapy to any site within 4 weeks before the randomization;
Serious, non-healing wound, ulcer, or bone fracture;
Evidence of bleeding diathesis or coagulopathy;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BevacizumabAlso: AvastinThis is the treatment assigned to experimental arm: All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn.	Drug	Bevacizumab in combination with FOLFIRI chemotherapy
CetuximabAlso: ErbituxThis is the treatment assigned to control arm: All treatments will continue until disease progression, death, unacceptable toxicity, clinical decision or consent withdrawn.	Drug	Cetuximab in combination with FOLFIRI chemotherapy
5-FUAlso: 5 FluorouracilFOLFIRI 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	Bevacizumab in combination with FOLFIRI chemotherapy, Cetuximab in combination with FOLFIRI chemotherapy
IrinotecanAlso: IrinotecanoFOLFIRI 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	Bevacizumab in combination with FOLFIRI chemotherapy, Cetuximab in combination with FOLFIRI chemotherapy
Calcium levofolinateAlso: Levofolinic acidFOLFIRI 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	Bevacizumab in combination with FOLFIRI chemotherapy, Cetuximab in combination with FOLFIRI chemotherapy

Primary outcome

Progression free survival (PFS) in patients with RASmut at liquid biopsy and RASwt on tissue.
Time frame: From the date of randomization to the date of first progression or death for any cause, whichever occurs first, assessed up to 36 months
The primary objective of the study is to assess whether the combination of bevacizumab plus chemotherapy is superior to cetuximab plus chemotherapy in terms of progression free survival (PFS) in patients with RASmut at liquid biopsy and RASwt on tissue.

5 secondary outcomes

Overall survival (OS)
Time frame: up to 36 months
Objective response rate (ORR)
Time frame: up to 36 months
Prevalence of RAS mutation
Time frame: up to 36 months
Patients Safety
Time frame: up to 36 months
Compliance
Time frame: up to 36 months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2026.
Individual participant dataSharing planned: No

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The IMPACT Study - Identification of Men With a Genetic Predisposition to ProstAte Cancer
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Erika Gervasi study chair

AUSL IRCCS Reggio Emilia

Irene De Simone study chair

Istituto Di Ricerche Farmacologiche Mario Negri

4 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bevacizumab, Cetuximab and 5-FU in people with Colorectal Cancer and Metastatic Colorectal Cancer, run by Azienda USL Reggio Emilia - IRCCS at 4 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression free survival (PFS) in patients with RASmut at liquid biopsy and RASwt on tissue. (time frame: From the date of randomization to the date of first progression or death for any cause, whichever occurs first, assessed up to 36 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04776655.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2026.