CAPRI-3 Phase 3 clinical study to evaluate the use of continuing cetuximab treatment beyond first line progression in molecular selected metastatic colorectal cancer patients

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

21 Jul 2025 → ongoing

Decision date (initial)

2025-06-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To investigate the efficacy in terms of Objective Response Rate (ORR) of chemotherapy doublet plus cetuximab as second line treatment in molecular selected wild type metastatic colorectal cancer patients compared to chemotherapy doublet plus bevacizumab. 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 objectives 3

1. To evaluate the Progression Free Survival (PFS) of chemotherapy doublet plus cetuximab as second line treatment in molecular selected metastatic colorectal cancer patients compared to chemotherapy doublet plus bevacizumab.
2. To evaluate the Overall Survival (OS) of chemotherapy doublet plus cetuximab as second line treatment in molecular selected metastatic colorectal cancer patients compared to chemotherapy doublet plus bevacizumab
3. Toxicity of the trial drugs

Conditions and MedDRA coding

metastatic colorectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Histologically proven diagnosis of colorectal adenocarcinoma.
2. Diagnosis of metastatic disease.
3. Efficacy of a first line therapy containing anti-EGFR drug with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1) or a prolonged (at least 6 months) stable disease.
4. Progression to first line therapy.
5. RAS and BRAF wild-type status of FFPE analysis of primary colorectal cancer and/or related metastasis.
6. RAS (NRAS and KRAS exon 2,3 and 4), BRAFV600E, PIK3CA, EGFR ECD wild-type and HER2 not amplified in liquid biopsy at the time of screening (according to NGS, Foundation/Roche).
7. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST criteria, vers.1.1).
8. Male or female patients ≥ 18 years of age.
9. ECOG Performance Status 0-1.
10. Adequate bone marrow, liver and renal function assessed within 14 days before starting study treatment as defined by the following parameters: Bone marrow: • Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L • Hemoglobin (Hgb) ≥ 9 g/dL • Platelets ≥ 100 x 109/L Liver function: • Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and ALT (SGPT) ≤ 2.5 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT ≤ 5 x ULN Renal function: • Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min
11. If female and of childbearing potential, have a negative result on a pregnancy test performed a maximum of 7 days before initiation of study treatment.
12. If female and of childbearing potential, or if male, agreement to use adequate contraception (e.g., abstinence, intrauterine device, oral contraceptive, or double-barrier method), during the study and until at least 3 months after last dose of study treatment administration, based on the judgment of the Investigator or a designated associate.
13. Signed informed consent obtained before screening.

Exclusion criteria 18

1. Any contraindication to the use of cetuximab, bevacizumab, Irinotecan, 5-FU, oxaliplatin, folic acid.
2. Active uncontrolled infections, active disseminated intravascular coagulation or history of interstitial lung disease.
3. Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin cancer or in situ carcinoma of the cervix.
4. Pregnancy (exclusion to be ascertained by a beta hCG test).
5. Breastfeeding.
6. Fertile women (<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception.
7. Myocardial infarction, unstable angina pectoris, balloon angioplasty (PTCA) with or without stenting within the past 12 months before inclusion in the study, Grade III or IV heart failure (NYHA classification).
8. Cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin.
9. Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study.
10. Participation in a clinical study or experimental drug treatment within 30 days prior to study inclusion or during participation in the study.
11. Known or clinically suspected brain metastases
12. History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhea.
13. Severe, non-healing wounds, ulcers or bone fractures
14. Marked proteinuria (nephrotic syndrome).
15. Known DPD deficiency (specific screening not required).
16. Known history of alcohol or drug abuse.
17. A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study.
18. Absent or restricted legal capacity.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The Overall Response Rate (ORR) according to 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 3

1. Progression Free Survival (PFS) according to RECIST 1.1 defined as the time from random assignment in the clinical trial to disease progression or death from any cause.
2. The Overall Survival (OS) defined as the interval from enrollment to death for every cause.
3. The safety profile of the trial drugs as measured by the incidence of AEs, SAEs, clinical laboratory assessments, vital signs, physical examination, ECG parameters, and ECOG PS.

Investigational products

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

Test 1

Comparator 1

Auxiliary 4

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

Fortunato Ciardiello

Public contact point

Organisation

Gruppo Oncologico Dell'Italia Meridionale

Contact name

Fortunato Ciardiello

Locations

2 EU/EEA countries · 41 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

Results and documents

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

Documents 24 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