Tests sotorasib with panitumumab and 5-fluorouracil in colorectal cancer

Trial details

Who runs it

Federation Francophone de Cancerologie Digestive

Trial code

NCT07124884EU 2024-514030-20-00

Record updated

15 August 2025

Original description

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 CRCRead full original descriptionShow less

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

Inclusion: 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: 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); Immunotherapy within 3 months before the beginning of the treatment study; Patients treated by brivudine within 4 weeks before the first dose of study treatment, or concomitant treatment with brivudine; Administration of live or live attenuated vaccine within 30 days prior to the first dose of study treatment start; 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; Uncontrolled intercurrent illness including liver (liver cirrhosis Child Pugh B or C) and lung (one second forced expiratory volume <50%) severe insufficiency; Patient with potentially serious infection; 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; 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; 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; Patients with high microsatellite instability (MSI-H) or a tumour with mismatched repair (dMMR); Patients with Dihydropyrimidine Dehydrogenase (DPD) enzyme deficiencies (uracilemia ≥ 16 ng/mL); Patient under treatment by strong CYP3A4 inducers; 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.

ClinicalTrials.gov NCT07124884 · EU CTIS 2024-514030-20-00