Background: GastroIntestinal Stromal Tumors (GIST) are paradigmatic models of cancers with a driver mutation of an oncogene, in which imatinib is recommended as adjuvant therapy or treatment of locally advanced and metastatic forms. After failure of imatinib (either progression or toxicity), sunitinib and regorafenib are indicated as 2^nd and 3^rd lines, respectively. Beyond approved drugs, tyrosine kinase inhibitors (TKI) can bring clinical benefit because some clones remain sensitive to TKI. Lenvatinib is a broad spectrum TKI targeting KIT, RET, PDGFRA, VEGFR 1-3 and FGFR 1-4, that is approved in the treatment of differentiated thyroid carcinoma and metastatic renal cell carcinoma and hepatocellular carcinoma. Methods: This prospective, randomized, placebo-controlled, double-blinded, multicenter trial evaluates the efficacy and safety of Lenvatinib in adult GIST patients (pts) who failed at least to previous imatinib and sunitinib. Seventy-four pts will be randomly allocated in a 1:1 ratio to receive either oral lenvatinib, at a daily dose of 24mg, or its matching placebo, continuously, until progression of disease (PD) or unacceptable toxicity. Randomization will be stratified according to the number of different previous anticancer drugs (2 or > 2). The primary objective is to compare the Progression-free survival (PFS) between arms. The expected median PFS are 1.5 month in the control arm and 3.0 months in the experimental arm (HR = 0.5). Seventy one events will provide 90% power to show significant improvement in PFS, using a 2-sided log-rank test at a 10% level. Secondary endpoints include the overall survival, the objective response rate, the best overall response, the quality of life and the safety profile. Patients allocated in the placebo arm who experience PD (RECIST 1.1) may switch to active lenvatinib. Radiological endpoints will be evaluated using the RECIST 1.1. Translational objectives will be to identify blood and tumor parameters as predictive markers of lenvatinib efficacy. Recruitment has been activated in January 2020. Ten participating sites of the French Sarcoma Group will participate in the trial. Clinical trial information: NCT04193553.