CAPRI 2 GOIM Study: Investigate the Efficacy and Safety of a Bio-marker Driven Cetuximab-based Treatment Regimen

NCT ID: NCT05312398

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 219 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-07-15
• Study Completion Date: 2026-08-15

Brief Summary

This clinical program aims to evaluate the activity and efficacy of cetuximab continuation of treatment for three lines of therapy with rotation of chemotherapy (FOLFIRI, FOLFOX, irinotecan) in mCRC patients, whose tumors remain RAS/BRAF WT. The study will also evaluate the activity and efficacy of cetuximab re-introduction in combination with irinotecan as third line therapy in the concept of re-challenge for those patients that will be treated in second line with chemotherapy plus anti-angiogenic drugs (FOLFOX plus bevacizumab), having a RAS or BRAF mutant disease at the time of progression after FOLFIRI plus cetuximab first line treatment. A novel characteristic of this program is that the therapeutic algorithm will be defined at each treatment decision (first line, second line and third line) in a prospective fashion in each patient by liquid biopsy assessment of RAS/BRAF status.

Detailed Description

Based on dynamic and longitudinal liquid biopsy assessment of RAS/BRAF status, that will be prospectively performed before each line of treatment, mCRC patients will be treated with cetuximab in combination with chemotherapy throughout three lines of therapy, as follows: FOLFIRI plus cetuximab (first line); FOLFOX plus cetuximab (second line); irinotecan plus cetuximab (third line) in case of RAS/BRAF WT at each time point of progression. If at progression after the first line, the liquid biopsy assessment indicates RAS and or BRAF mutant status, patients will be treated with FOLFOX plus bevacizumab as the second line of therapy. If at progression after the second line, the liquid biopsy assessment indicates RAS and or BRAF mutant status, patients will be treated with regorafenib or trifluridine-tipiracil (investigator's choice), as third line of therapy. Each treatment will be administered using standard doses and schedules until progression of disease or unacceptable toxicity.

This study will also evaluate the activity and efficacy of cetuximab re-introduction in combination with irinotecan as third line therapy in the concept of re-challenge for those patients that will be treated in second line with FOLFOX plus bevacizumab, having a RAS or BRAF mutant disease at the time of progression after FOLFIRI plus cetuximab first line treatment. A novel characteristic of this program is that the therapeutic algorithm will be defined at each treatment decision (first line, second line and third line) in a prospective fashion in each patient by liquid biopsy assessment of RAS/BRAF status

Conditions

Metastatic Colorectal Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

single arm

This is an open-label phase II study investigating 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. Based on dynamic and longitudinal liquid biopsy assessment of RAS/BRAF status, that will be prospectively performed before each line of treatment, mCRC patients will be treated with cetuximab in combination with chemotherapy throughout three lines of therapy, as follows:

• FOLFIRI plus cetuximab (first line);
• FOLFOX plus cetuximab (second line);
• irinotecan plus cetuximab (third line).

If at progression after the first line or after the second line, the liquid biopsy assessment indicates RAS and or BRAF mutant status, patients will be treated with FOLFOX plus bevacizumab as second line of therapy, or with regorafenib or with trifluridine-tipiracil (investigator's choice) as third line therapy.

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

I LINE:

• FOLFIRI + cetuximab

FOLFIRI: 200 mg L-folinic acid with 180 mg/ m² irinotecan over 1.30 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days.

Cetuximab: 400 mg/m2 initial dose (120-minute IV infusion on cycle 1 day 1), then 250 mg/m2 once weekly thereafter

II LINE:

• FOLFOX + cetuximab

FOLFOX: 200 mg L-folinic acid given concurrently with 85 mg/ m² oxaliplatin over 2 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days.

Cetuximab: as I line

THIRD LINE:

• Irinotecan + cetuximab

Irinotecan: 180 mg/ m² irinotecan over 1.30 h, IV infusion every 2 weeks. Cetuximab: as I line

FOLFIRI

Intervention Type: DRUG

I LINE:

• FOLFIRI + cetuximab

FOLFIRI: 200 mg L-folinic acid given concurrently with 180 mg/ m² irinotecan over 1.30 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days.

Cetuximab: 400 mg/m2 initial dose (120-minute IV infusion on cycle 1 day 1), then 250 mg/m2 once weekly thereafter

FOLFOX regimen

Intervention Type: DRUG

II LINE:

• FOLFOX + cetuximab

FOLFOX: 200 mg L-folinic acid given concurrently with 85 mg/ m² oxaliplatin over 2 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days.

Cetuximab: as I line

Irinotecan

Intervention Type: DRUG

III LINE:

• Irinotecan + cetuximab

Irinotecan: 180 mg/ m² irinotecan over 1.30 h, IV infusion every 2 weeks. Cetuximab: as I line

Interventions

Cetuximab

I LINE:

• FOLFIRI + cetuximab

FOLFIRI: 200 mg L-folinic acid with 180 mg/ m² irinotecan over 1.30 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days.

Cetuximab: 400 mg/m2 initial dose (120-minute IV infusion on cycle 1 day 1), then 250 mg/m2 once weekly thereafter

II LINE:

• FOLFOX + cetuximab

FOLFOX: 200 mg L-folinic acid given concurrently with 85 mg/ m² oxaliplatin over 2 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days.

Cetuximab: as I line

THIRD LINE:

• Irinotecan + cetuximab

Irinotecan: 180 mg/ m² irinotecan over 1.30 h, IV infusion every 2 weeks. Cetuximab: as I line

Intervention Type: DRUG

FOLFIRI

I LINE:

• FOLFIRI + cetuximab

FOLFIRI: 200 mg L-folinic acid given concurrently with 180 mg/ m² irinotecan over 1.30 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days.

Cetuximab: 400 mg/m2 initial dose (120-minute IV infusion on cycle 1 day 1), then 250 mg/m2 once weekly thereafter

Intervention Type: DRUG

FOLFOX regimen

II LINE:

• FOLFOX + cetuximab

FOLFOX: 200 mg L-folinic acid given concurrently with 85 mg/ m² oxaliplatin over 2 h IV infusion, followed by a 400 mg/ m² IV bolus of fluorouracil followed by 2400 mg/ m² fluorouracil IV infusion over 46 h every 14 days.

Cetuximab: as I line

Intervention Type: DRUG

Irinotecan

III LINE:

• Irinotecan + cetuximab

Irinotecan: 180 mg/ m² irinotecan over 1.30 h, IV infusion every 2 weeks. Cetuximab: as I line

Intervention Type: DRUG

Other Intervention Names

Erbitux; FOLFOX

Eligibility Criteria

Inclusion Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Campania Luigi Vanvitelli

OTHER

Sponsor Role: lead

Responsible Party

Fortunato Ciardiello

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Fortunato Ciardiello

Role: PRINCIPAL_INVESTIGATOR

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

Locations

A.O.U. Ospedali Riuniti

Ancona, AN, Italy

Ente Ecclesiastico Ospedale Generale Regionale 'F. Miulli'

Acquaviva delle Fonti, BA, Italy

IRCCS Istituto Tumori 'Giovanni Paolo II'

Bari, BA, Italy

Ospedale IRCCS 'Saverio de Bellis'

Castellana Grotte, BA, Italy

Ospedale Sacro Cuore di Gesù - FATEBENEFRATELLI

Benevento, BN, Italy

P.O. Antonio Perrino

Brindisi, BR, Italy

A.O.U. Cagliari - Presidio Policlinico D. Casula

Monserrato, CA, Italy

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

Catania, CT, Italy

A.O.U. Mater Domini

Catanzaro, CZ, Italy

Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, FG, Italy

P.O. 'Vito Fazzi'

Lecce, LE, Italy

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

Tricase, LE, Italy

Istituto Europeo di Oncologia

Milan, MI, Italy

A.O.U. Policlinico 'P. Giaccone'

Palermo, PA, Italy

Istituto Oncologico Veneto IRCCS

Padua, PD, Italy

A.O.U. Pisana

Pisa, PI, Italy

A.O. San Carlo

Potenza, PZ, Italy

A.U.S.L. - IRCCS di Reggio Emilia - P.O. Arcispedale S.Maria Nuova

Reggio Emilia, RE, Italy

A.S.P. Ragusa - Ospedale Maria Paternò Arezzo

Ragusa, RG, Italy

A.O. San Camillo-Forlanini

Roma, RM, Italy

Fondazione Policlinico Universitario 'Agostino Gemelli' IRCCS

Roma, RM, Italy

Ospedale San Giuseppe Moscati

Statte, TA, Italy

A.O. Ordine Mauriziano

Torino, TO, Italy

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

Napoli, , Italy

Istituto Nazionale Tumori 'Fondazione G. Pascale'

Napoli, , Italy

Countries

Italy

References

Martini G, Ciardiello D, Napolitano S, Martinelli E, Troiani T, Latiano TP, Avallone A, Normanno N, Di Maio M, Maiello E, Ciardiello F. Efficacy and safety of a biomarker-driven cetuximab-based treatment regimen over 3 treatment lines in mCRC patients with RAS/BRAF wild type tumors at start of first line: The CAPRI 2 GOIM trial. Front Oncol. 2023 Feb 13;13:1069370. doi: 10.3389/fonc.2023.1069370. eCollection 2023.

Reference Type: DERIVED

PMID: 36860319 (View on PubMed)

Other Identifiers

CAPRI2-MS062202-0123

Identifier Type: -

Identifier Source: org_study_id