Investigate the efficacy and safety of a bio-marker driven cetuximab-based treatment regimen over 3 treatment lines in mCRC patients with RAS/BRAF wt tumors at start of first line.

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

1 Jul 2021 → ongoing

Decision date (initial)

2024-12-09

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Serono S.p.A.

External identifiers

EU CT number

2024-518534-81-00

EudraCT number

2020-003008-15

ClinicalTrials.gov

NCT05312398

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To investigate the efficacy and safety of a biomarker-driven cetuximab-based treatment regimen over 3 treatment lines in patients with RAS/BRAF wild type (WT) mCRC at start of first line therapy.

Secondary objectives 4

1. Progression free survival (PFS) for each line
2. Overall survival (OS)
3. Safety profile
4. Quality of life (QoL)

Conditions and MedDRA coding

metastatic colorectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Histologically proven diagnosis of colorectal adenocarcinoma
2. Diagnosis of metastatic disease
3. RAS and BRAF wild-type status of FFPE analysis of primary colorectal cancer and/or related metastasis
4. Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST criteria, vers.1.1)
5. Male or female patients ≥ 18 years of age
6. ECOG Performance Status 0,1
7. 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
8. 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
9. 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
10. Signed informed consent obtained before screening.

Exclusion criteria 20

1. Any contraindication to the use of cetuximab, Irinotecan, 5-FU, oxaliplatin, folinic acid,bevacizumab, trifluridine-tipiracil, regorafenib
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. Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before entering the study
11. Participation in a clinical study or experimental drug treatment within 30 days prior to study inclusion or during participation in the study
12. Known or clinically suspected brain metastases
13. History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea
14. Severe, non-healing wounds, ulcers or bone fractures
15. Uncontrolled hypertension
16. Marked proteinuria (nephrotic syndrome)
17. Known DPD deficiency (specific screening not required)
18. Known history of alcohol or drug abuse
19. A significant concomitant disease which, in the investigating physician's opinion, rules out the patient's participation in the study
20. Absent or restricted legal capacity

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Response rate (RR) for each line of treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in patients with RAS/BRAF wild type (WT) mCRC.

Secondary endpoints 4

1. Progression Free Survival (PFS): measured from the start of therapy until the first observation of disease progression or death due to any cause.
2. Overall Survival (OS): calculated from the start of the study treatment until death.
3. Safety: Adverse events graded according NCI CTCAE v 5.0.
4. Molecular profiles of tumor tissue and liquid biopsy: molecular analysis of formalin fixed paraffin embedded (FFPE) tumor tissue, which is representative of the primary tumor or of a metastatic site at the diagnosis of mCRC, will be performed before the first line, whilst blood samples for liquid biopsy will be collected before each line of treatment.

Investigational products

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

Test 1

Auxiliary 7

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

1 EU/EEA country · 24 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 9 files

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

Application history

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