A phase II single arm interventional trial evaluating the activity and safety of combination between CABOzantinib and TEMozolomide (TMZ) in lung and GEP-NENs progressive after SSAs, everolimus, sunitinib or PRRT-CABOTEM

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Introduction: Cabozantinib (Cbz), a tyrosine kinase inhibitor, and Temozolomide (TMZ), an alkylating agent, show relevant clinical implications in neuroendocrine neoplasms (NENS). In glioma patients, the combination of Cbz and TMZ was well tolerated even with the addition of radiotherapy. It is possible to hypothesize a synergistic combination of Cbz and TMZ. Cbz, through the inhibition of the c-MET pathway, could enhance the sensitivity of NENs to TMZ. In addition, the intermittent metronomic schedule of TMZ has a proven anti-angiogenic activity that could be additive and/or enhance the anti-angiogenic effect of Cbz.

Aim(s): The aim of the Cabotem trial is to evaluate the efficacy and safety of Cabozantinib in combination with TMZ as a treatment in lung and GEP-NENs progressive after SSAs, everolimus, sunitinib or PRRT.

Materials and methods: This is a phase II, open‐label, single‐arm, multicentre study. All patients are treated with Cbz 40 mg per os daily continuously, and TMZ 100 mg/m2/day seven days followed by seven days of stop. Enrollment started in June 2021, 35 patients will be enrolled over a planned recruitment period of 24 months. The primary endpoint is to assess the synergistic effects of Cbz plus TMZ evaluated on overall response rate, as assessed by RECIST v1.1. The secondary endpoints is progression-free survival (PFS) and overall survival, 1-year overall survival. Exploratory endpoints include the evaluation of biomarkers and biologic studies through IHC expression of HGF, RET, c-MET, VEGFR2, AXL. The MGMT in the tumor samples of treated patient will be evaluated to identify possible predictive factors.

Conference:

Presenting Author:

Authors: Clemente O, Starita N, Cives M, Bracigliano A, Badalamenti G,

Keywords: neuroendocrine, Cabozantinb, Temozolomide, treatment, clinical trial, NEN,