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 (COLOSOTO)

August 14, 2025 updated by: Federation Francophone de Cancerologie Digestive

COLOSOTO: Single-arm Phase II Study Evaluating 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

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

COLOSOTO is a multicenter, open-label, prospective single-arm phase II trial, sponsored and cordinated by the Fédération Francophone de Cancérologie Digestive (FFCD) in collaboration with the ENGIC group (European Network in GastroIntestinal Cancer), evaluating 5-FU plus Panitumumab and Sotorasib as first line treatment in patients with MSS/pMMR KRAS G12C mutated unresectable CRC. Inclusion will begin in September 2025, for 36 months. Overall, patients from 40 European sites will be included (in France, Germany, Italy and Spain).

The main inclusion and exclusion criteria are summarized in Table 1. Main inclusion criteria are patients ≥18 years old, with unresectable MSS/pMMR KRASG12C metastatic CRC histologically proven, with altered WHO Performance Status...

Eligible patients will receive LV5FU2 (a 400mg/m2 intravenous (IV) bolus of 5-FU at day 1 (D1) with 400mg/m2 of folinic acid, followed by a continuous 5-FU infusion of 2400mg/m2 over 46 hours) plus Panitumumab (6mg/kg IV at D1) and Sotorasib (960mg PO once daily, every day) in 2-week-cycles (Q2W) until progression or intolerance (cf Figure 1).

Adverse events requiring dose adjustment or treatment discontinuation will all be assessed using the NCI-CTCAE v5.0 scale and manage in accordance with the standard guidelines and the "Summaries of Product Characteristics".

The primary objective is to evaluate the progression-free survival (PFS) of 5FU plus Panitumumab and Sotorasib at 8 months in first-line treatment of patients non-eligible for a doublet/triplet chemotherapy with advanced unresectable KRAS G12C mutated CRC. The progression will be defined as the radiological progression according to RECIST v1.1 criteria assessed by the investigator. A centralized review of CT-scans will be performed to confirm RECIST 1.1 criteria.

Secondary objectives include median progression-free survival (mPFS), disease control rate (DCR), time to progression (TTP), overall survival (OS), best objective response rate (ORR), duration of response (DoR), safety profile, Quality of life (QoL) (with EORTC QLQC30 and FACIT-GP5 questionnaires), and Geriatric assessment (based on G8 score and " Geriatric COre Data sEt " (G-CODE)).

Toxicity will all be evaluated according to the National cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.0) scale. A safety analysis will be done when 10 patients have been treated for at least 2 months to check the good tolerability of 5-FU plus Panitumumab and Sotorasib combination

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France
      • Annecy, France
      • Antony, France
      • Aurillac, France
      • Bayeux, France
        • Centre hospitalier
        • Contact:
      • Bayonne, France
      • Beauvais, France
      • Besançon, France
      • Bezannes, France
      • Bordeaux, France
        • Bordeaux Nord Aquitaine
        • Contact:
      • Bordeaux, France
      • Brest, France
        • CHU Morvan
        • Contact:
      • Béthune, France
      • Caen, France
        • CHU Côte de Nacre
        • Contact:
      • Cholet, France
      • Colmar, France
      • Compiègne, France
      • Dijon, France
      • Dijon, France
        • Gf Leclerc
        • Contact:
      • Dijon, France
        • Institut de cancérologie de Bourgogne GRReCC
        • Contact:
      • Grenoble, France
        • Groupe Hospitalier Mutualiste
        • Contact:
      • La Roche-sur-Yon, France
      • Levallois-Perret, France
      • Lille, France
      • Limoges, France
      • Lorient, France
        • Groupe Hospitalier Bretagne Sud
        • Contact:
      • Lyon, France
      • Marseille, France
      • Marseille, France
        • Hopital Europeen
        • Contact:
      • Nancy, France
      • Orsay, France
      • Paris, France
      • Paris, France
      • Paris, France
      • Paris, France
      • Pau, France
      • Pessac, France
      • Plérin, France
      • Poitiers, France
      • Quimper, France
      • Reims, France
        • CHU Robert Debré
        • Contact:
      • Reims, France
      • Saint-Denis, France
      • Saint-Grégoire, France
      • Saint-Malo, France
        • Groupe Hospitalier Rance Emeraude
        • Contact:
      • Saint-Mandé, France
      • Strasbourg, France
        • Clinique Sainte-Anne
        • Contact:
      • Strasbourg, France
      • Tours, France
      • Villefranche-sur-Saône, France
        • Hopital Nord Ouest
        • Contact:
  • Germany
      • Bochum, Germany
      • Frankfurt, Germany
        • Krankenhaus Nordwest-CH Frankfurt Am Main
        • Contact:
          • Oliver GOTZE Thorsten
          • Phone Number: +49 (069) 76 01-44 20
      • Göttingen, Germany
        • Universitätsmedizin Göttingen CHU
        • Contact:
          • Ute Margarethe KONIG
      • Hamburg, Germany
        • Hämatologisch Onkologische Praxis Eppendorf
        • Contact:
  • Italy
      • Aviano, Italy
        • Centro di Riferimento Oncologico di Aviano
        • Contact:
          • Luisa FOLTRAN
      • Catania, Italy
        • Azienda Ospedaliero Universitaria Policlinico Rodolico San Marco Di Catania
        • Contact:
          • Giuseppe NOVELLO
      • Firenze, Italy
        • Azienda Ospedaliero Universitaria Careggi
        • Contact:
          • Lorenzo Antonuzzo
      • Livorno, Italy
        • Azienda Unita Sanitaria Locale 6 Livorno
        • Contact:
          • Giacomo ALLEGRINI
      • Meldola, Italy
        • Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori
        • Contact:
          • Alessandro PASSARDI
      • Milano, Italy
        • Fondazione IRCCS Istituto Nazionale Dei Tumori
        • Contact:
          • Filippo PIETRANTONIO
      • Monserrato, Italy
        • Azienda Ospedaliero-Universitatia Di Cagliari
        • Contact:
          • Mario SCARTOZZI
      • Padova, Italy
        • Istituto Oncologico Veneto
        • Contact:
          • Francesca BERGAMO
      • Pisa, Italy
        • Azienda Ospedaliero-Universitaria Pisana
        • Contact:
          • Roberto MORETTO
      • Prato, Italy
        • Azienda Usl Toscana Centro
        • Contact:
          • Samantha DI DONATO
      • Ravenna, Italy
        • Azienda Unità Sanitaria Locale della Romagna
        • Contact:
          • Stefano TAMBERI
      • Roma, Italy
        • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
        • Contact:
          • Lisa SALVATORE
      • Roma, Italy
        • Azienda Ospedaliera Policlinico Universitario Tor Vergata
        • Contact:
          • Vincenzo Formica
      • San Giovanni Rotondo, Italy
        • Casa Sollievo Della Sofferenza
        • Contact:
          • Tiziana PIA LATIANO
      • Torino, Italy
        • Azienda Ospedaliero-Universitaria Città della salute e della scienza di Torino Presidio Molinette
        • Contact:
          • Massimo DI MAIO
      • Tricase, Italy
        • Pia Fondazione Di Culto E Religione Card Panico
        • Contact:
          • Emiliano TAMBURINI
      • Udine, Italy
        • Azienda Sanitaria Universitaria Friuli Centrale
        • Contact:
          • Valentina FANOTTO
  • Spain
      • Barcelona, Spain
        • Hospital Universitari Vall d'Hebron
        • Contact:
      • Cordoba, Spain
        • Hospital Universitario Reina Sofia
        • Contact:
      • L'Hospitalet De Llobregat, Spain
        • Instituto Catalán de Oncología. Hospital Duran i Reynals
        • Contact:
      • Madrid, Spain
        • Hospital Universitario Gregorio Marañón
        • Contact:
      • Oviedo, Spain
        • Hospital Universitario Central de Asturias
        • Contact:
      • Pamplona, Spain
      • Salamanca, Spain
        • Hospital Clinico Universitario de Salamanca
        • Contact:
          • Maria del Rosario Vidal Tocino
      • San Carlos, Spain
        • Hospital Universitario Clínico San Carlos
        • Contact:
          • Javier Sastre Valera
      • Valencia, Spain
        • Consorcio Hospital General Universitario de Valencia
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

- 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.
  • Hypersensitivity to one of the active substances or to one of the excipients of the trial treatments.
  • Patient with interstitial lung disease or pulmonary fibrosis.
  • Patients with history of interstitial pneumonitis or pulmonary fibrosis.
  • Has a known psychiatric or substance abuse disorder that would interfere with the patient's ability to cooperate with the requirements of the study.
  • Patient who is under judicial protection and patient who is legally institutionalized or under guardianship or not able to give consent.
  • Pregnant or breastfeeding woman.
  • Inability to undergo the medical follow-up of the trial for geographical, social or psychological reasons.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 5-fluorouracil plus Panitumumab and Sotorasib
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)
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patient alive or without progression 8 months after inclusion.
Time Frame: at 8 months after the 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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival (OS)
Time Frame: up to 2 years after inclusion.
Overall survival was defined as the time from the date of inclusion to the patient's death (all causes). For alive patients, the date of the latest news was taken into account.
up to 2 years after inclusion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federation Francophone de Cancerologie Digestive

Collaborators

Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Arbeitsgemeinschaft fur Internistische Onkologie
Northwest Oncology Cooperative Group(GONO)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 31, 2025

Primary Completion (Estimated)

June 30, 2030

Study Completion (Estimated)

December 30, 2030

Study Registration Dates

First Submitted

August 8, 2025

First Submitted That Met QC Criteria

August 14, 2025

First Posted (Estimated)

August 15, 2025

Study Record Updates

Last Update Posted (Estimated)

August 15, 2025

Last Update Submitted That Met QC Criteria

August 14, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRODIGE 107-ENGIC01-COLOSOTO
  • 2024-514030-20-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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