ArticleBMC cancer2024
Randomized phase 2 study of valproic acid combined with simvastatin and gemcitabine/nab-paclitaxel-based regimens in untreated metastatic pancreatic adenocarcinoma patients: the VESPA trial study protocol.
Article in BMC cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05821556 (Randomized Phase 2 Study of Valproic Acid combinEd With Simvastatin and Gemcitabine/Nab-paclitaxel-based Regimens in Untreated Metastatic Pancreatic Adenocarcinoma Patients), which is not on this map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized Phase 2 Study of Valproic Acid combinEd With Simvastatin and Gemcitabine/Nab-paclitaxel-based Regimens in Untreated Metastatic Pancreatic Adenocarcinoma Patients (The VESPA Trial).
Who cites it
8 citing papers in PubMed.
- Biomarker-Driven Strategies for Stromal Reprogramming in Pancreatic Ductal Adenocarcinoma.Cells · 2026Review
- The histone acylation network: emerging therapeutic targets for remodeling the epigenetic landscape in pancreatic ductal adenocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Targeting cholesterol-driven immunometabolism in cancer: from molecular circuits to clinical translation.Molecular cancer · 2026Review
- Mevalonate pathway in pancreatic ductal adenocarcinoma: Mechanisms driving metabolic and cellular plasticity.Cancer pathogenesis and therapy · 2026Review
- Identification of EFNA3 as candidate prognosis marker and potential therapeutic target for adrenocortical carcinoma.Oncology letters · 2025Article
- A Critical Appraisal of Off-Label Use and Repurposing of Statins for Non-Cardiovascular Indications: A Systematic Mini-Update and Regulatory Analysis.Journal of clinical medicine · 2025Article
- Valproic acid improves the efficacy of oxaliplatin/fluoropyrimidine-based chemotherapy by targeting cancer stem cell via β-Catenin modulation in colorectal cancer.Cell death & disease · 2025Article
- Mechanism of valproic acid-induced hepatic steatosis via enhancing NRF2-FATP2-mediated fatty acid uptake.Theranostics · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
Abstract
backgroundMetastatic pancreatic ductal adenocarcinoma (mPDAC) patients have very poor prognosis highlighting the urgent need of novel treatments. In this regard, repurposing non-oncology already-approved drugs might be an attractive strategy to offer more-effective treatment easily tested in clinical trials. Accumulating evidence suggests 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 pancreatic cancer and statins have been shown to have a direct antitumor effect when used alone or in combination therapy. We recently showed capability of VPA/Simvastatin (SIM) combination to potentiate the antitumor activity of gemcitabine/nab-paclitaxel in vitro and in vivo PDAC preclinical models. METHODS/
designVESPA 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) versus chemotherapy alone (standard arm) in mPDAC patients. The study involves Italian and Spanish oncology centers and includes an initial 6-patients safety run-in-phase. A sample size of 240 patients (120 for 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 to 9 months in the experimental arm. Secondary endpoints are overall survival, response rate, disease control rate, duration of response, CA 19.9 reduction, toxicity, and quality of life. The study includes a patient engagement plan and complementary biomarkers studies on tumor and blood samples.
conclusionsVESPA is the first trial evaluating efficacy and safety of two repurposed drugs in oncology such as VPA and SIM, in combination with standard chemotherapy, with the aim of improving mPDAC survival. The study is ongoing. Enrollment started in June 2023 and a total of 63 patients have been enrolled as of June 2024.
trial registrationEudraCT number: 2022-004154-63; ClinicalTrials.gov identifier NCT05821556, posted 2023/04/20.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.