Clinical trial · Observational
RAS Mutations in ctDNA and Anti-EGFR reINTROduction in mCRC (RASINTRO)
Predictive Impact of RAS Mutations in Circulating Tumor DNA for Efficacy of Anti-EGFR Reintroduction Treatment in Patients With Metastatic Colorectal Cancer
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
Some data have suggested a clinical survival benefit related to the reintroduction of anti-EGFRs therapy in patients with metastatic colorectal cancer (mCRC). Based on resistance mechanisms related to the development of resistant clones, the investigators could assume that patients who benefited most from the reintroduction of anti-EGFRs were those who, through interval chemotherapy, had no longer mutated RAS clone in plasma that appeared during the progression with the first anti-EGFR treatment. Conversely, those who did not benefit from this therapy were probably patients who had mutated RAS clones circulating at the time of reintroduction of anti-EGFRs. To support this hypothesis, investigators propose to evaluate the correlation between the eventual presence of RAS mutations in circulating blood and the efficacy of an anti-EGFR therapy reintroduction in patients with mCRC.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Metastatic Colorectal Cancer | Malignant Colorectal Neoplasm | CURATED_BROADER | 0.80 |
Interventions
Interventions (0)
Data not yet available
Design
Arms and outcomes
Arms (1)
- label
- Patients with metastatic colorectal cancer
- description
- Rechallenge with an anti-EGFR monoclonal antibody in patients with metastatic colorectal cancer
Primary outcomes (1)
- measure
- Progression-free survival (PFS)
- timeFrame
- Time from the date of beginning the reintroduction of anti-EGFR therapy to date of tumor progression or death from any cause, whichever occurred first, assessed up to 6 months.
- description
- PFS will be evaluated according to the RAS mutations on circulating tumor DNA status
Secondary outcomes (2)
- measure
- Tumor response
- timeFrame
- The tumor response will be assessed in patients with measurable lesions according to RECIST criteria version 1.1, assessed up to 6 months
- description
- Tumor response will be evaluated according to the RAS mutations on circulating tumor DNA
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Age ≥18 years * Metastatic colorectal cancer histological confirmed without somatic mutations of KRAS (exons 2, 3 et 4) and NRAS (exons 2, 3 et 4) * Apart from contraindication, patients should have already received fluoropyrimidine, irinotecan, oxaliplatin, anti-EGFR (panitumumab or cetuximab) and anti-angiogenic (bevacizumab or aflibercept) therapies * Previous treatment with anti-EGFR-based chemotherapy (panitumumab or cetuximab) should have provided an objective tumor response (according to RECIST 1.1 criteria) and/or PFS ≥ 4 months. * At least one line of interval chemotherapy between the last cycle of anti-EGFR based treatment and reintroduction of anti-EGFR therapy * Signed written informed consent obtained prior to any study specific screening procedures Exclusion Criteria: * Discontinuation of first anti-EGFR therapy for other reasons than tumor progression * Previous malignancy other than colorectal cancer in the last 5 years * Medical, sociological, psychological or legal conditions that would not permit the patient to sign the informed consent
References
Publications (12)
- RESULTVan Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pinter T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. doi: 10.1056/NEJMoa0805019. PMID 19339720
- RESULTDouillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. doi: 10.1200/JCO.2009.27.4860. Epub 2010 Oct 4. PMID 20921465
- RESULTAmado RG, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman DJ, Juan T, Sikorski R, Suggs S, Radinsky R, Patterson SD, Chang DD. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008 Apr 1;26(10):1626-34. doi: 10.1200/JCO.2007.14.7116. Epub 2008 Mar 3. PMID 18316791
- RESULTKarapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008 Oct 23;359(17):1757-65. doi: 10.1056/NEJMoa0804385. PMID 18946061
- RESULTDouillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocakova I, Ruff P, Blasinska-Morawiec M, Smakal M, Canon JL, Rother M, Williams R, Rong A, Wiezorek J, Sidhu R, Patterson SD. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med. 2013 Sep 12;369(11):1023-34. doi: 10.1056/NEJMoa1305275. PMID 24024839