5-fluorouracil Plus Panitumumab (Anti-EGFR) and Sotorasib (KRAS G12C Inhibitor) in First-line Treatment of Patients Non-eligible for a Doublet/Triplet Chemotherapy With Advanced Unresectab

NCT07124884 | Not Yet Recruiting Phase 2

• 2 other identifiers: PRODIGE 107-ENGIC01-COLOSOTO2024-514030-20-00
• Study Type: interventional
• Target: 300
• Locations: 4 countries
• Sites: 80

Brief Summary

5-fluorouracil (5-FU) is a standard of care in frail/elderly patients with an unresectable colorectal adenocarcinoma (CRC) in first-line setting. Panitumumab plus Sotorasib are promising in advanced line in KRAS G12C mutated CRC. In this study, We assess the safety and efficacy of 5FU combination with Panitumumab and Sotorasib as first-line treatment in frail/elderly patients with unresectable KRAS G12C mutated CRC

Conditions

Colorectal Carcinoma; KRAS G12C Mutation; Unresectable Colorectal Cancer

Keywords

sotorasib; colorectal cancer; KRAS G12C

Outcome Measures

Primary Outcomes (1)

• Percentage of patient alive or without progression 8 months after inclusion.

  Progression will be assessed by the investigator according to recist 1.1 based on images performed every 8 weeks even in case of deferred treatments. Clinical progression will not be considered as an event.

  at 8 months after the inclusion.

Secondary Outcomes (1)

• Overall survival (OS)

  up to 2 years after inclusion.

Study Arms (1)

5-fluorouracil plus Panitumumab and Sotorasib

EXPERIMENTAL

Each patient receives one treatment cycle every two weeks until disease progression or unacceptable toxicity. Panitumumab is administered at a dose of 6 mg/kg via intravenous infusion over one hour during the first cycle, and over 30 minutes from the second cycle onward. The LV5FU2 regimen includes folinic acid (400 mg/m², or 200 mg/m² if levo-leucovorin is used) as a two-hour IV infusion, followed by a 5-FU bolus (400 mg/m² over 10 minutes), and a continuous 5-FU infusion (2400 mg/m² over 46 hours). Sotorasib is given orally at a dose of 960 mg once daily on a continuous basis.

Drug: Administration of experimental treatment association (sotorasib, panitumumab 5FU)

Interventions

Administration of experimental treatment association (sotorasib, panitumumab 5FU) DRUG

Panitumumab is administered at a dose of 6 mg/kg via intravenous infusion over one hour during the first cycle, and over 30 minutes from the second cycle onward. The LV5FU2 regimen includes folinic acid (400 mg/m², or 200 mg/m² if levo-leucovorin is used) as a two-hour IV infusion, followed by a 5-FU bolus (400 mg/m² over 10 minutes), and a continuous 5-FU infusion (2400 mg/m² over 46 hours). Sotorasib is given orally at a dose of 960 mg once daily on a continuous basis.

5-fluorouracil plus Panitumumab and Sotorasib

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years.
• Histologically proven advanced-stage unresectable locally advanced or metastatic colorectal adenocarcinoma.
• Proven KRAS G12C mutation as locally assessed by means of an IVDR-compliant test
• Agreement to participate to biological studies (blood samples for ctDNA and send tumour block).
• Patient with one these criteria:
• Patient with WHO PS=2 Patient between 70 and 75 years old with WHO PS 1 Patient ≥ 75 years old
• Measurable lesion according to the Response Evaluation Criteria in Solid Tumours 1.1 (RECIST 1.1).
• No prior treatment for the metastatic disease. Prior adjuvant chemotherapy is allowed if there is more than 6 months between the end of adjuvant treatment and relapse.
• Adequate organ function: Hemoglobin \> 9 g/dl, Absolute neutrophil count \> 1500 /mm3, Platelets \> 80 000/mm3, Creatinine clearance rate ≥50 mL/min as calculated using MDRD formula, ALT/AST ≤5×ULN and total bilirubin ≤1.5×ULN.
• Ability to understand and sign written informed consent to participate in the study.
• Provides written informed consent for the study.
• Life expectancy \>6 months.
• Women of childbearing potential must agree to use contraception during the trial treatment and for at least 6 months after discontinuation of the experimental treatments. Men who have sexual relationship with women of childbearing potential must agree to use contraception during treatment and for at least 3 months after discontinuation of the experimental treatments.
• Patient affiliated to a social security scheme for France, or equivalent for other countries.

You may not qualify if:

• \- Patient with one of these criteria: Patient fit for doublet/triplet regimen Patient with WHO PS 3 or 4 Patient \< 75 years old with WHO PS 0 Patient \< 70 years old with WHO PS 0 or 1
• Uncontrolled intercurrent illness including liver (liver cirrhosis Child Pugh B or C) and lung (one second forced expiratory volume \<50%) severe insufficiency.
• Patients with high microsatellite instability (MSI-H) or a tumour with mismatched repair (dMMR).
• Clinically significant cardiac abnormalities including prior history of any of the following: severe cardiomyopathy, congestive heart failure of New York Heart Association grade ≥3, history of clinically significant (i.e., active) atherosclerotic cardiovascular disease (myocardial infarction, unstable angina, cerebrovascular accident within 6 months prior to the first dose of study treatments).
• Patients with Dihydropyrimidine Dehydrogenase (DPD) enzyme deficiencies (uracilemia ≥ 16 ng/mL).
• Immunotherapy within 3 months before the beginning of the treatment study.
• Patient under treatment by strong CYP3A4 inducers.
• Patients treated by brivudine within 4 weeks before the first dose of study treatment, or concomitant treatment with brivudine.
• Patient with potentially serious infection.
• Administration of live or live attenuated vaccine within 30 days prior to the first dose of study treatment start.
• Poor nutritional state (albuminemia \< 25 g/L or weight loss \> 10% during the last month).
• Hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption.
• Other malignancy within 2 years prior to study enrolment, except for localized cancer in situ, basal or squamous cell skin cancer adequately treated.
• Less than 4 weeks from major surgeries and not recovered adequately from the procedure and/or any complications from the surgery.
• Patients with persistent toxicities related to prior treatment of grade greater than 1.Is c urrently participating in or has participated in a study of an investigational agent or has used an investigational device within 3 weeks or 5 half-lives (whichever longer) before study entry.

Sponsors & Collaborators

• Federation Francophone de Cancerologie Digestive: lead
• Northwest Oncology Cooperative Group(GONO): collaborator
• Arbeitsgemeinschaft fur Internistische Onkologie: collaborator
• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): collaborator

Study Sites (80)

ICO site Paul Papin

Angers, France

Location

Centre Hospitalier Annecy Genevois

Annecy, France

Location

Hôpital Privé

Antony, France

Location

Centre Hospitalier

Aurillac, France

Location

Centre Hospitalier

Bayeux, France

Location

Ch Cote Basque

Bayonne, France

Location

Ch Simone Veille

Beauvais, France

Location

Chu Jean Minjoz

Besançon, France

Location

Polyclinique Courlancy

Bezannes, France

Location

Centre Hospitalier Béthune Beuvry

Béthune, France

Location

Bordeaux Nord Aquitaine

Bordeaux, France

Location

TIVOLI

Bordeaux, France

Location

Chu Morvan

Brest, France

Location

CHU Côte de Nacre

Caen, France

Location

Centre Hospitalier

Cholet, France

Location

Hôpitaux civils

Colmar, France

Location

Polyclinique Saint-Côme

Compiègne, France

Location

Chu Francois Mitterand

Dijon, France

Location

Gf Leclerc

Dijon, France

Location

Institut de cancérologie de Bourgogne GRReCC

Dijon, France

Location

Groupe Hospitalier Mutualiste

Grenoble, France

Location

Chd Vendee

La Roche-sur-Yon, France

Location

Hôpital Franco Britannique

Levallois-Perret, France

Location

Hôpital Privé Le Bois

Lille, France

Location

CHU Dupuytren

Limoges, France

Location

Groupe Hospitalier Bretagne Sud

Lorient, France

Location

Hôpital Jean Mermoz

Lyon, France

Location

Chu La Timone

Marseille, France

Location

Hôpital Européen

Marseille, France

Location

CHRU

Nancy, France

Location

Gh Nord Essone

Orsay, France

Location

Chu Cochin

Paris, France

Location

HEGP

Paris, France

Location

Montsouris

Paris, France

Location

Saint-Louis

Paris, France

Location

Centre Hospitalier

Pau, France

Location

CHU Haut Leveque

Pessac, France

Location

Centre Cario

Plérin, France

Location

Chu La Miletrie

Poitiers, France

Location

CH Quimper Concarneau

Quimper, France

Location

Cac Jean Godinot

Reims, France

Location

Chu Robert Debré

Reims, France

Location

Centre Hospitalier

Saint-Denis, France

Location

Hôpital Privé

Saint-Grégoire, France

Location

Hia Begin

Saint-Mandé, France

Location

Groupe Hospitalier Rance Emeraude

St-Malo, France

Location

Clinique Sainte-Anne

Strasbourg, France

Location

ICANS

Strasbourg, France

Location

CHRU Trousseau

Tours, France

Location

Hôpital Nord Ouest

Villefranche-sur-Saône, France

Location

Saint Joseph Hospital Bochum

Bochum, Germany

Location

Krankenhaus Nordwest-CH Frankfurt Am Main

Frankfurt, Germany

Location

Universitätsmedizin Göttingen CHU

Göttingen, Germany

Location

Hämatologisch Onkologische Praxis Eppendorf

Hamburg, Germany

Location

Centro Di Riferimento Oncologico Di Aviano

Aviano, Italy

Location

Azienda Ospedaliero Universitaria Policlinico Rodolico San Marco Di Catania

Catania, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, Italy

Location

Azienda Unita Sanitaria Locale 6 Livorno

Livorno, Italy

Location

Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori

Meldola, Italy

Location

Fondazione IRCCS Istituto Nazionale Dei Tumori

Milan, Italy

Location

Azienda Ospedaliero-Universitatia Di Cagliari

Monserrato, Italy

Location

Istituto Oncologico Veneto

Padua, Italy

Location

Azienda Ospedaliero-Universitaria Pisana

Pisa, Italy

Location

Azienda USL Toscana Centro

Prato, Italy

Location

Azienda Unita Sanitaria Locale Della Romagna

Ravenna, Italy

Location

Azienda Ospedaliera Policlinico Universitario Tor Vergata

Roma, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, Italy

Location

Casa Sollievo Della Sofferenza

San Giovanni Rotondo, Italy

Location

Azienda Ospedaliero-Universitaria Città della salute e della scienza di Torino Presidio Molinette

Torino, Italy

Location

Pia Fondazione Di Culto E Religione Card Panico

Tricase, Italy

Location

Azienda Sanitaria Universitaria Friuli Centrale

Udine, Italy

Location

Hospital Universitari Vall d'Hebron

Barcelona, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Spain

Location

Instituto Catalan de Oncologia. Hospital Duran i Reynals

L'Hospitalet de Llobregat, Spain

Location

Hospital Universitario Gregorio Maranon

Madrid, Spain

Location

Hospital Universitario Central de Asturias

Oviedo, Spain

Location

Hospital Universitario de Navarra

Pamplona, Spain

Location

Hospital Clinico Universitario de Salamanca

Salamanca, Spain

Location

Hospital Universitario Clinico San Carlos

San Carlos, Spain

Location

Consorcio Hospital General Universitario de Valencia

Valencia, Spain

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

sotorasib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2025
• First Posted: August 15, 2025
• Study Start: August 31, 2025
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): December 30, 2030
• Last Updated: August 15, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (17); FR (50); DE (4); ES (9)