Romance

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gruppo Oncologico Dell'Italia Meridionale

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Mar 2026 → ongoing

Decision date (initial)

2026-01-19

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective is to demonstrate the superiority of irinotecan plus cetuximab compared with trifluridine/tipiracil plus bevacizumab in terms of ORR.

Secondary objectives 2

1. To evaluate the clinical activity (PFS and OS) of irinotecan plus cetuximab rechallenge therapy compared with trifluridine/tipiracil plus bevacizumab. Other secondary objectives include the evaluation of safety, tolerance and the impact on quality of life of irinotecan plus cetuximab and trifluridine/tipiracil plus bevacizumab combination. Data regarding the efficacy of the subsequent line of treatment will be recorded.
2. Efficacy of the subsequent line of treatment (Exploratory objectives)

Conditions and MedDRA coding

metastatic colorectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 20

1. 1. Male or female aged ≥18 years
2. 2. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≤1
3. 3. Diagnosis of histologically or cytologically confirmed colorectal cancer.
4. 4. At least one measurable lesion according to RECIST1.1
5. 5. KRAS/NRAS/BRAFV600E wt status of primary CRC or related metastasis (local laboratory assessment).
6. 6. Progression to previous first-line anti-EGFR-containing therapy producing at least a partial response ≥ 6 months.
7. 7. Received and progressed to an anti-EGFR and irinotecan free second-line treatment.
8. 8. Have an anti-EGFR free interval of at least 4 months.
9. 9. Refractory to previous 5-fluorouracil/capecitabine, irinotecan, oxaliplatin, bevacizumab.
10. 10. RAS/BRAF/EGFR/PIK3CAex20/ MAP2K1/MET WT and HER2 not amplified ctDNA at FoundationOne CDx test at baseline.
11. 11. Life expectancy of at least 3 months.
12. 12. 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).
13. 13. 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).
14. 14. Adequate renal function defined by an estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
15. 15. No contraindication to the study drugs.
16. 16. No prior treatment with trifluridine/tipiracil.
17. 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.
18. 18. 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.
19. 19. Will and ability to comply with the protocol.
20. 20. Signed informed consent obtained before screening.

Exclusion criteria 15

1. ECOG PS ≥2
2. 2. Received more than 2 lines of treatment for metastatic disease.
3. 3. Previous treatment with trifluridine/tipiracil
4. 4. RAS/BRAF/EGFR/PIK3CAex20/ MAP2K1/MET alterations and HER2 amplified tumors at liquid biopsy analysis during screening
5. 5. 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.
6. 6. Evidence of bleeding diathesis or coagulopathy.
7. 7. Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy.
8. 8. 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).
9. 9. Clinically significant cardiovascular disease, active inflammatory bowel disease, active autoimmune disease.
10. 10. Diagnosis of interstitial pneumonitis or pulmonary fibrosis.
11. 11. History of abdominal fistula, GI perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to the first study treatment.
12. 12. Pregnant or lactating women.
13. 13. Psychiatric or addictive disorders would preclude study participation.
14. 14. Active uncontrolled infections or other clinically relevant concomitant illness contraindicating study treatments.
15. 15. Withdrawal of the consent to take part to the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ORR by RECIST 1.1 defined as the proportion of patients who have a partial or complete response to therapy. An external radiology department will receive the images of radiological re-evaluations from the participating sites. The imaging will be assessed by a blind operator

Secondary endpoints 4

1. 1. PFS defined as the time from random assignment in the clinical trial to disease progression or death from any cause.
2. 2. OS defined as the interval from enrollment to death for every cause.
3. 3. The safety profile of the trial drugs as measured by the incidence of AEs evaluated using the NCI- CTCAE version 5.0 (CTCAE v 5.0), SAEs, clinical laboratory assessments, vital signs, physical examination, ECG parameters, and ECOG PS
4. 4. Quality of life (QoL) questionnaire (EORTC QLQ-C30)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gruppo Oncologico Dell'Italia Meridionale

Sponsor organisation

Gruppo Oncologico Dell'Italia Meridionale

Address

Viale John Fitzgerald Kennedy 50

City

Bari

Postcode

70124

Country

Italy

Scientific contact point

Organisation

Gruppo Oncologico Dell'Italia Meridionale

Contact name

Davide Ciardiello

Public contact point

Organisation

Gruppo Oncologico Dell'Italia Meridionale

Contact name

Davide Ciardiello

Locations

1 EU/EEA country · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications