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Metastatic Colorectal Cancer (CRC)Phase 2ROMANCE - GOIMNCT07381764

ROMANCE: "Irinotecan Plus Cetuximab Rechallenge Versus Trifluridine/Tipiracil Plus Bevacizumab in Molecularly Selected Metastatic Colorectal Cancer"

A Phase 2 study testing Erbitux (Cetuximab), Bevacizumab and Irinotecan in people with Metastatic Colorectal Cancer (CRC), run by Gruppo Oncologico Italia Meridionale at 26 sites in Italy.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This study is a phase II, open-label, multicenter clinical trial designed to evaluate two different treatment options for patients with metastatic colorectal cancer whose disease has progressed after standard therapies. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer (CRC)
What is being tested?
Erbitux (Cetuximab), Bevacizumab and Irinotecan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
150 participants
Where
26 sitesItaly
Study dates
20 Mar 2026to 30 Mar 2031
Phase
Phase 2
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

  • Male or female aged ≥18 years
  • Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤1
  • Diagnosis of histologically or cytologically confirmed colorectal cancer.
  • At least one measurable lesion according to RECIST1.1
  • KRAS/NRAS/BRAFV600E wt status of primary CRC or related metastasis (local laboratory assessment).
  • Progression to previous first-line anti-EGFR-containing therapy producing at least a partial response ≥ 6 months.
Show all 21Show fewer
  • Received and progressed to an anti-EGFR and irinotecan free second-line treatment.
  • Have an anti-EGFR free interval of at least 4 months.
  • Refractory to previous 5-fluorouracil/capecitabine, irinotecan, oxaliplatin, bevacizumab.
  • RAS/BRAF/EGFR/PIK3CAex20/MAP2K1/MET WT and HER2 not amplified ctDNA at FoundationOne CDx test at baseline.
  • Life expectancy of at least 3 months.
  • Adequate hematological function defined by white blood cell (WBC) count ≥ 2.5 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused).
  • Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN for all subjects or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
  • Adequate renal function defined by an estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
  • No contraindication to the study drugs.
  • No prior treatment with trifluridine/tipiracil.
  • Women of childbearing potential* must have a negative blood pregnancy test at thescreening visit. Subjects and their partners must be willing to avoid pregnancy during the trial.
  • A woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.
  • Women of childbearing potential, or male, must agree to use adequate contraception (e.g., abstinence, intrauterine device, oral contraceptive, or double-barrier method), during the study and until at least 6 months after last dose of study treatment administration, based on the judgment of the Investigator or a designated associate.
  • Will and ability to comply with the protocol.
  • Signed informed consent obtained before screening.

Who cannot join

  • ECOG PS ≥2
  • Received more than 2 lines of treatment for metastatic disease.
  • Previous treatment with trifluridine/tipiracil
  • RAS/BRAF/EGFR/PIK3CAex20/MAP2K1/MET WT HER2 not amplified status at liquid biopsy analysis during screening.
  • Previous history of malignancy within the last 2 years will be excluded with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ
  • Evidence of bleeding diathesis or coagulopathy.
Show all 15Show fewer
  • Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.
  • Known severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v 5 Grade ≥ 3), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).
  • Clinically significant cardiovascular disease, active inflammatory bowel disease, active autoimmune disease.
  • Diagnosis of interstitial pneumonitis or pulmonary fibrosis.
  • History of abdominal fistula, GI perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to the first study treatment.
  • Pregnant or lactating women.
  • Psychiatric or addictive disorders would preclude study participation.
  • Active uncontrolled infections or other clinically relevant concomitant illness contraindicating study treatments.
  • Withdrawal of the consent to take part to the study.

Trial locations and contacts

26 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Davide Ciardiello DC Principal Investigator contact

02/94372686

davide.ciardiello@ieo.it

26 sites in 1 country

Italy26 sites, 26 recruiting

  • Azienda Ospedaliero Universitaria "SS Antonio e Biagio e Cesare Arrigo"

    Alessandria

    Giulia Piacentini Principal Investigator, 0131 206893, giulia.piacentini@ospedale.al.it

    Recruiting

  • A.O.U. Ospedali Riuniti

    Ancona

    Rossana Berardi Principal Investigator, 071/5965715, rossana.berardi@ospedaliriuniti.marche.it

    Recruiting

  • Centro di Riferimento Oncologico (CRO), IRCCS

    Aviano

    Luisa Foltran Principal Investigator, 0434 399652, luisa.foltran@cro.it

    Recruiting

  • A.O.R.N. "Sant'anna e San Sebastiano"

    Caserta

    Michele Orditura Principal Investigator, 0823232515, michele.orditura@aorncaserta.it

    Recruiting

  • Ospedale IRCCS 'Saverio de Bellis'

    Castellana Grotte

    Claudio Lotesoriere Principal Investigator, 080/4994688, claudio.lotesoriere@irccsdebellis.it

    Not yet recruiting

  • A.R.N.A.S. Garibaldi - P.O. Garibaldi-Nesima

    Catania

    Roberto Bordonaro Principal Investigator, 095/7595936, rbordonaro63@gmail.com

    Not yet recruiting

  • Azienda Ospedaliero-Universitaria Renato Dulbecco

    Catanzaro

    Pierosandro Tagliaferri Principal Investigator, 0961/3694324, tagliaferri@unicz.it

    Not yet recruiting

  • A.O.U. Careggi

    Florence

    Lorenzo Antonuzzo Principal Investigator, 0557947298, lorenzo.antonuzzo@unifi.it

    Recruiting

  • Istituto Romagnolo per lo Studio dei Tumori 'Dino Amadori'

    Meldola

    Alessandro Passardi Principal Investigator, alessandro.passardi@irst.emr.it

    Recruiting

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan

    Andrea Sartore-Bianchi Principal Investigator, 02/64443708, andrea.sartorebianchi@unimi.it

    Recruiting

  • Fondazione IRCCS Istituto Nazionale Tumori

    Milan

    Filippo Pietrantonio Principal Investigator, 02/23903807, filippo.pietrantonio@istitutotumori.mi.it

    Recruiting

  • Istituto Europeo di Oncologia

    Milan

    Davide Ciardiello Principal Investigator, 02/94372686, davide.ciardiello@ieo.it

    Recruiting

  • Casa di Cura Villa Maria

    Mirabella Eclano

    Antonio Febbraro Principal Investigator, 0825 407301, antoniofebbraro@virgilio.it

    Recruiting

  • AOU Policlinico di Modena

    Modena

    Fabio Gelsomino Principal Investigator, 059 4222230, gelsomino.fabio@aou.mo.it

    Recruiting

  • A.O.U. dell'Università degli studi della Campania "Luigi Vanvitelli"

    Naples

    Giulia Martini Principal Investigator, 081/5666760, GIULIA.MARTINI@unicampania.it

    Recruiting

  • Istituto Nazionale Tumori 'Fondazione G. Pascale'

    Naples

    Antonio Avallone Principal Investigator, 081/5903629, a.avallone@istitutotumori.na.it

    Recruiting

  • Istituto Oncologico Veneto IRCCS

    Padova

    Francesca Bergamo Principal Investigator, francesca.bergamo@iov.veneto.it

    Recruiting

  • ARNAS Civico - Di Cristina-Benfratelli - P. O. 'Civico e Benfratelli'

    Palermo

    Marco Messina Principal Investigator, 340.4034246, marco.messina@arnascivico.it

    Not yet recruiting

  • Casa di cura Macchiarella

    Palermo

    Alfredo Colombo Principal Investigator, 3355273795, Alfredocolombo63@gmail.com

    Not yet recruiting

  • A.O.U. Pisana

    Pisa

    Chiara Cremolini Principal Investigator, 050/992192, chiaracremolini@gmail.com

    Recruiting

  • Fondazione Policlinico Universitario 'Agostino Gemelli' IRCCS

    Roma

    Giampaolo Tortora Principal Investigator, 06/30155202, giampaolo.tortora@policlinicogemelli.it

    Recruiting

  • Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza

    San Giovanni Rotondo

    Tiziana Pia Latiano Principal Investigator, 0882/410716, latiano.tiziana@gmail.com

    Not yet recruiting

  • A.O.U. Sassari

    Sassari

    Alessio Cogoni Principal Investigator, 079/2644636, alessio.cogoni@aouss.it

    Recruiting

  • Ospedale San Giuseppe Moscati

    Statte

    Salvatore Pisconti Principal Investigator, 099/4585810, salvatore.pisconti@asl.taranto.it

    Recruiting

  • A.O. 'Pia Fondazione Cardinale G. Panico'

    Tricase

    Maria Laura Iaia Principal Investigator, 0833.773111, iaia.mlaura4@gmail.com

    Not yet recruiting

  • ASST Sette Laghi-Ospedale di Circolo Fondazione Macchi

    Varese

    Michele Ghidini Principal Investigator, 0332278558, michele.ghidini@asst-settelaghi.it

    Recruiting

Other trials in Italy

About this study

Official title: ROMANCE GOIM Study: A Phase II, Open Label, Multicenter Trial Investigating Irinotecan Plus Cetuximab Rechallenge Compared With Trifluridine/Tipiracil Plus Bevacizumab as Third Line Treatment in Circulating Tumor DNA Molecularly Selected Metastatic Colorectal Cancer

This study is a phase II, open-label, multicenter clinical trial designed to evaluate two different treatment options for patients with metastatic colorectal cancer whose disease has progressed after standard therapies. The study compares a rechallenge treatment using irinotecan plus cetuximab with the current standard of care, trifluridine/tipiracil plus bevacizumab, as third-line therapy. Patients enrolled in the study are selected based on specific molecular characteristics of their cancer, identified through circulating tumor DNA analysis from a blood sample. The main purpose of the study is to determine whether the rechallenge with irinotecan and cetuximab leads to a higher tumor response rate compared with trifluridine/tipiracil plus bevacizumab. Secondary objectives include evaluating progression-free survival, overall survival, safety, and quality of life. Patients will be randomly assigned to one of the two treatment groups and will receive treatment until disease progression, unacceptable side effects, or withdrawal of consent. Tumor response will be assessed using standard imaging techniques according to RECIST criteria.

Read the detailed description

This is a phase II, open-label, randomized, multicenter clinical trial designed to evaluate the efficacy and safety of an anti-EGFR rechallenge strategy compared with the current standard of care in patients with molecularly selected metastatic colorectal cancer (mCRC). Eligible patients have metastatic colorectal cancer that has progressed after standard first- and second-line therapies and have previously achieved clinical benefit from an anti-EGFR-based regimen. Patient selection is based on molecular profiling performed on circulating tumor DNA obtained from a baseline blood sample, identifying tumors that are wild-type for RAS, BRAF, EGFR, PIK3CA exon 20, MAP2K1, and MET, and without HER2 amplification. A total of 150 patients will be randomized in a 1:1 ratio to one of two treatment arms. In the experimental arm, patients will receive cetuximab in combination with irinotecan administered every two weeks. In the control arm, patients will receive trifluridine/tipiracil administered orally according to standard dosing schedules in combination with bevacizumab administered every two weeks. Treatment in both arms will continue until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria. Tumor assessments will be performed at regular intervals using computed tomography or magnetic resonance imaging and evaluated according to RECIST version 1.1 criteria. The primary endpoint of the study is the objective response rate. Secondary endpoints include progression-free survival, overall survival, safety and tolerability, and quality of life assessed using validated questionnaires. Adverse events will be monitored throughout the study and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Following disease progression, crossover to the alternative treatment arm may be considered at the investigator's discretion. Long-term follow-up will be conducted to assess survival outcomes.

Being tested
Erbitux (Cetuximab), Bevacizumab, Irinotecan, Trifluridine/tipiracil
Medical subject headings
Colorectal Neoplasms

What participants receive

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

  • Erbitux (Cetuximab)Drug

    This is an anti-EGFR monoclonal antibody administered in combination with chemotherapy. The dose is 500 mg/m2 over 120 minutes

  • BevacizumabDrug

    This is an anti-VEGF monoclonal antibody used as an active comparator in the control arm of the study. The dose is 5 mg/Kg of body weight given once every 2 weeks.

  • IrinotecanDrug

    Irinotecan is a cytotoxic chemotherapy agent administered intravenously in combination with cetuximab the dose is 180 mg/m2 over 90 minutes, once every 2 weeks.

  • Trifluridine/tipiracilDrug

    Trifluridine/tipiracil is an oral antineoplastic combination administered in combination with bevacizumab as part of the control treatment arm. The dose is 5 mg/ m² twice daily on Days 1 to 5 and Days 8 to 12 on a cycle of 28 days.

Study groups in NCT07381764
Study groupRoleWhat they receive
Experimental: Arm A - Irinotecan + CetuximabExperimentalThis arm is for participants with molecularly selected metastatic colorectal cancer who have progressed after standard first- and second-line therapies and previously achieved clinical benefit from an anti-EGFR-based regimen. Participants randomized to this arm will receive irinotecan in combination with cetuximab as a rechallenge strategy. The objective of this arm is to evaluate the antitumor activity and safety of irinotecan plus cetuximab compared with the control treatment in the third-line setting.
Receives: Drug: Erbitux (Cetuximab); Drug: Irinotecan
Active Comparator: Arm B - Trifluridine/Tipiracil + BevacizumabActive comparatorThis arm is for participants with molecularly selected metastatic colorectal cancer who have progressed after standard first- and second-line therapies. Participants randomized to this arm will receive trifluridine/tipiracil in combination with bevacizumab, which represents the current standard of care in the third-line treatment setting. This arm serves as the control group for comparison with the experimental rechallenge strategy.
Receives: Drug: Bevacizumab; Drug: Trifluridine/tipiracil

What is being measured

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

  1. Objective Response Rate (ORR)

    Objective Response Rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria. Tumor assessments are based on radiological imaging reviewed centrally by an independent blinded radiology reviewe

    Measured: From Week 8 through disease progression or end of treatment, up to approximately 24 months.

Secondary outcomes (5)

  1. Progressio-Free Survival (PFS)

    Progression-Free Survival (PFS) is defined as the time from randomization to documented disease progression according to RECIST version 1.1 criteria or death from any cause, whichever occurs first.

    Measured: From date of randomization until the date of first documented disease progression per RECIST v1.1 or death from any cause, whichever occurs first, assessed up to 36 months.

  2. Overall Survival (OS)

    Overall Survival (OS) is defined as the time from enrollment to death from any cause.

    Measured: From date of enrollment until death from any cause, assessed up to 36 months.

  3. Incidence of Adverse Events and Serious Adverse Events

    Safety will be assessed by the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), as well as by changes in clinical laboratory parameters, vital signs, physical examinations, electrocardiogram (ECG) findings, and ECOG performance status. Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

    Measured: From first dose of study treatment until 30 days after the last dose of study treatment.

  4. Treatment Exposure as a Measure of Tolerability

    Tolerability will be assessed by the frequency of treatment discontinuations, dose reductions, and dose delays due to adverse events during study treatment.

    Measured: Through study completion, an average of approximately 24 months

  5. The impact of treatment with irinotecan plus cetuximab and trifluridine/tipiracil plus bevacizumab on quality of life

    The impact of treatment with irinotecan plus cetuximab and trifluridine/tipiracil plus bevacizumab on quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30).

    Measured: From baseline through study completion, an average of approximately 12 months

Timeline

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

  1. First posted2 Feb 2026
  2. Study start20 Mar 2026
  3. Primary completion30 Mar 2031 (estimated)
  4. Study completion30 Mar 2031 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
ARM A: Cetuximab + irinotecan (75 patients) ARM B: Trifluridine/tipiracil + bevacizumab (75 patients)
Masking
None (open label)
Enrolment
150 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07381764
Sponsor's protocol ID
ROMANCE - GOIM
Other IDs
2025-521319-38-00, 2025
Acronym
ROMANCE - GOIM
Status last verified
Sep 2026
First submitted
16 Jan 2026
Last updated
11 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • D'Agata AP, Pellizzari G, Martini G, Ghidini M, Napolitano S, Zampino MG, Fazio N, Pietrantonio F, Manca P, Sartore-Bianchi A, Puccini A, Corallo S, Zaniboni A, Piacentini G, Bergamo F, Gelsomino F, Foltran L, Passardi A, Cremolini C, Antonuzzo L, Tortora G, Berardi R, Avallone A, Orditura M, Arrichiello G, Santabarbara G, Febbraro A, Latiano TP, Lotesoriere C, Laura IM, Tagliaferri P, Colombo A, Messina M, Cogoni A, Pisconti S, Bordonaro R, Ciardiello F, Ciardiello D. Irinotecan Plus Cetuximab Rechallenge Versus Trifluridine/Tipiracil Plus Bevacizumab as Third-Line Treatment in Circulating Tumor DNA-Selected Metastatic Colorectal Cancer (ROMANCE Trial). Clin Colorectal Cancer. 2026 Oct 2:S1533-0028(26)00072-1. doi: 10.1016/j.clcc.2026.09.004. Online ahead of print.

    PubMed 42907240

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Erbitux (Cetuximab), Bevacizumab and Irinotecan in people with Metastatic Colorectal Cancer (CRC), run by Gruppo Oncologico Italia Meridionale at 26 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 21 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Contact Davide Ciardiello DC Principal Investigator (02/94372686, davide.ciardiello@ieo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) (time frame: From Week 8 through disease progression or end of treatment, up to approximately 24 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 NCT07381764, which also lists 1 linked publication.

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 11 Sep 2026.

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