1534TiP - Valproic acid combinEd with Simvastatin and gemcitabine/nab-paclitaxel-based regimens in untreated metastatic Pancreatic Adenocarcinoma patients-VESPA trial

Background

Metastatic pancreatic ductal adenocarcinoma (mPDAC) patients have very poor prognosis suggesting the urgent need of novel treatments. Repurposing non-oncology already-approved drugs might be an attractive strategy to offer more effective treatment easily tested in clinical trials. Accumulating evidences suggest that epigenetic deregulation is a hallmark of cancer contributing to treatment resistance in several solid tumors, including PDAC. Histone deacetylase inhibitors (HDACi) are epigenetic drugs we have investigated preclinically and clinically as anticancer agents. Valproic acid (VPA) is a generic low-cost anticonvulsant and mood stabilizer, with HDAC inhibitory activity and anticancer properties also demonstrated in PDAC models. Statins use was reported to be associated with lower mortality risk in patients with PDAC and statins have been shown to have a direct antitumor effect when used alone or in combination therapy. We recently demonstrated the capability of VPA/SIM combination to potentiate the antitumor activity of gemcitabine/nab-paclitaxel in vitro and in vivo PDAC preclinical models.

Trial design

VESPA is a patient-centric open-label randomized multicenter phase-II investigator-initiated trial, evaluating the feasibility, safety and efficacy of VPA/SIM plus first-line gemcitabine/nab-paclitaxel-based regimens (AG or PAXG) (experimental arm) vs chemotherapy alone (standard arm) in mPDAC patients. The study involves Italian and Spanish centers and includes an initial 6-patients safety run-in-phase in the experimental arm. A sample size of 240 patients (120 each arm) was calculated under the hypothesis that the addition of VPA/SIM to gemcitabine and nab-paclitaxel-based regimens may extend progression free survival from 6 months in the standard arm to 9 months in the experimental arm. Secondary endpoints are overall survival, response rate, disease control rate, duration of response, CA19.9 reduction, toxicity, and quality of life. The study includes a patient engagement plan and complementary biomarkers studies on tumor and blood samples. Trial recruitment commenced in June 2023 with 50 patients enrolled up to now.

Clinical trial identification

EudraCT 2022-004154-63; NCT05821556.

Editorial acknowledgement

Legal entity responsible for the study

Istituto Nazionale Tumori IRCCS G. Pascale.

Funding

REMEDi4ALL consortium, which has received funding from the European Union's Horizon Europe research and innovation programme under grant agreement No 101057442; and by the Italian Ministry Health- grant RF-2021-12371995.

Disclosure

All authors have declared no conflicts of interest.