A majority of patients with mCRC are not suitable for potentially curative resection and their management consists in palliative-intended chemotherapy (CT). Nevertheless, it is described that in patients who achieve complete response (CR) with CT alone or after multimodality treatment, median overall survival is significantly longer than in other patients. In combination with CT, anti-EGFR antibodies appear to be the biological agents of choice in order to reach the best response rate as long as tumors are RAS wild-type.To determine RAS and BRAF mutational status, we have already demonstrated the clinical validity and utility of circulating DNA (ctDNA) analysis using IntPlex® method. Selecting patients with this technology, we aim to investigate response rate and outcomes reached with panitumumab in combination with a standard (mFOLFOX6) or an intensified CT regimen (FOLFIRINOX) in RAS and BRAF wild-type (WT) metastatic patients.
This is a national multicentric open-label randomized phase II trial. Key inclusion criteria are age between 18 and 75 years, ECOG PS 0 and 1, untreated synchronous or metachronous metastatic disease deemed unresectable with curative intent, RAS and BRAF WT tumor according to analysis of ctDNA by Intplex® technology. 209 patients will be randomized 2:1 to either FOLFIRINOX-panitumumab (N = 139) or mFOLFOX6-panitumumab (N = 70)(12 planned cycles in each arm). For each arm, two strata are planned according to disease-extent (non/liver limited disease). Primary endpoint is the CR rate defined as complete disappearance of metastatic lesions and CEA level normalization. It can be reached with CT alone or with a multimodal approach. Secondary endpoints are progression-free and overall survival, secondary resection rate, early tumor shrinkage, depth of response, safety, diagnostic performance of ctDNA analysis. On-treatment, an ancillary study assesses appearance of RAS mutations in ctDNA detected by Intplex® technology. The first patient was enrolled in October 2017 and > 20 sites are planned to recruit patients.
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T. Mazard: Research funding: Roche and Amgen; Honoraria: Amgen, Sanofi, BMS; Travel accommodations, expenses: Amgen. All other authors have declared no conflicts of interest.