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

NCT05312398 | Active Not Recruiting Phase 2

• 1 other identifier: CAPRI2-MS062202-0123
• Study Type: interventional
• Target: 219
• Locations: 1 country
• Sites: 25

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.

Conditions

Metastatic Colorectal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• RR

  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) mCRCregimen over 3 treatment lines in patients with RAS/BRAF wild type (WT) mCRC at start of first line therapy

  up to 59 months

Secondary Outcomes (5)

• PFS

  from 8 weeks to 59 months (from the start of therapy until the first observation of disease progression or death due to any cause)

• OS

  up to 59 months

• AE

  from screening up to 59 months

• EORTC Core Quality of Life questionnaire EORTC QLQ C30

  At screening, for each line of therapy at Week 4, at Week 25 of treatment start and at progression

• DERMATOLOGY LIFE QUALITY INDEX (DLQI)

  at screening, for each line of therapy at Week 4, at Week 25 of treatment start and at progression

Other Outcomes (4)

• Explorative objective: RR for each line of therapy

  from screening up to 23 months

• Exploratory objective: cumulative PFS

  from screening up to 23 months

• Explorative objective: overall survival

  from screening up to 23 months

Study Arms (1)

single arm

EXPERIMENTAL

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.

Drug: Cetuximab; Drug: FOLFIRI; Drug: FOLFOX regimen; Drug: Irinotecan

Interventions

Cetuximab 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

Also known as: Erbitux

single arm

FOLFIRI 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

single arm

FOLFOX regimen 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

Also known as: FOLFOX

single arm

Irinotecan DRUG

III LINE: \- Irinotecan + cetuximab Irinotecan: 180 mg/ m² irinotecan over 1.30 h, IV infusion every 2 weeks. Cetuximab: as I line

single arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven diagnosis of colorectal adenocarcinoma
• Diagnosis of metastatic disease
• RAS and BRAF wild-type status of FFPE analysis of primary colorectal cancer and/or related metastasis
• Measurable disease according to Response Evaluation Criteria in Solid Tumors RECIST criteria, vers.1.1)
• Male or female patients ≥ 18 years of age
• ECOG Performance Status 0,1
• 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

You may not qualify if:

• Any contraindication to the use of cetuximab, Irinotecan, 5-FU, oxaliplatin, folinic acid,bevacizumab, trifluridine-tipiracil, regorafenib
• Active uncontrolled infections, active disseminated intravascular coagulation or history of interstitial lung disease
• 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
• Breastfeeding
• Fertile women (\<2 years after last menstruation) and men of childbearing potential not willing to use effective means of contraception•
• Cardiac arrhythmias requiring anti-arrhythmic therapy, with the exception of beta blockers or digoxin
• Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study
• Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before entering the study
• Known or clinically suspected brain metastases
• History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea
• Severe, non-healing wounds, ulcers or bone fractures
• Uncontrolled hypertension
• Marked proteinuria (nephrotic syndrome)
• Known DPD deficiency (specific screening not required)
• Known history of alcohol or drug abuse

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead

Study Sites (25)

A.O.U. Ospedali Riuniti

Ancona, AN, Italy

Location

Ente Ecclesiastico Ospedale Generale Regionale 'F. Miulli'

Acquaviva delle Fonti, BA, Italy

Location

IRCCS Istituto Tumori 'Giovanni Paolo II'

Bari, BA, Italy

Location

Ospedale IRCCS 'Saverio de Bellis'

Castellana Grotte, BA, Italy

Location

Ospedale Sacro Cuore di Gesù - FATEBENEFRATELLI

Benevento, BN, Italy

Location

P.O. Antonio Perrino

Brindisi, BR, Italy

Location

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

Monserrato, CA, Italy

Location

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

Catania, CT, Italy

Location

A.O.U. Mater Domini

Catanzaro, CZ, Italy

Location

Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza

San Giovanni Rotondo, FG, Italy

Location

P.O. 'Vito Fazzi'

Lecce, LE, Italy

Location

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

Tricase, LE, Italy

Location

Istituto Europeo di Oncologia

Milan, MI, Italy

Location

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

Palermo, PA, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, PD, Italy

Location

A.O.U. Pisana

Pisa, PI, Italy

Location

A.O. San Carlo

Potenza, PZ, Italy

Location

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

Reggio Emilia, RE, Italy

Location

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

Ragusa, RG, Italy

Location

A.O. San Camillo-Forlanini

Roma, RM, Italy

Location

Fondazione Policlinico Universitario 'Agostino Gemelli' IRCCS

Roma, RM, Italy

Location

Ospedale San Giuseppe Moscati

Statte, TA, Italy

Location

A.O. Ordine Mauriziano

Torino, TO, Italy

Location

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

Napoli, Italy

Location

Istituto Nazionale Tumori 'Fondazione G. Pascale'

Napoli, Italy

Location

Related Publications (1)

• 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.

  PMID: 36860319 DERIVED

MeSH Terms

Interventions

Cetuximab; IFL protocol; Folfox protocol; Irinotecan

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Fortunato Ciardiello

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 3 treatment lines in mCRC patients with RAS/BRAF wt tumors at start of first line.

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: April 5, 2022
• Study Start: July 15, 2021
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): August 15, 2026
• Last Updated: May 25, 2025

Record last verified: 2025-05

Locations

IT (25)