Study Background and Disease Burden
Endometrial cancer represents one of the most common gynecologic malignancies, with a rising global incidence and significant mortality in advanced or recurrent stages. Patients with recurrent advanced/metastatic disease face limited effective therapeutic options beyond first-line treatments, and prognosis remains poor. Molecular profiling has revealed that endometrial cancers frequently harbor alterations in critical pathways including PI3K-AKT-mTOR, insulin-like growth factor 1 (IGF1), and DNA repair mechanisms. These molecular derangements drive tumor progression and confer resistance to conventional treatments. Consequently, a therapeutic strategy simultaneously targeting multiple dysregulated pathways holds promise to enhance treatment efficacy. The ENDOLA phase I/II clinical trial was thus designed to explore the combination of three agents — the PARP inhibitor olaparib, metronomic low-dose cyclophosphamide, and metformin, which acts as an inhibitor of PI3K-AKT-mTOR signaling — in women with recurrent advanced or metastatic endometrial carcinomas, aiming to improve disease control in a heavily pretreated population.
