Combining Valproic Acid and Simvastatin with Gemcitabine and Nab-paclitaxel for Metastatic Pancreatic Cancer

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).

This study is testing if adding valproic acid and simvastatin to standard chemotherapy can help people with untreated metastatic pancreatic cancer live longer without their disease getting worse.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 240 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: National Cancer Institute, Naples (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 5 sites (Naples, Italy and 4 other locations)
• Trial ID: NCT05821556 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial investigates the effectiveness of valproic acid and simvastatin in enhancing the efficacy of standard chemotherapy regimens using gemcitabine and nab-paclitaxel in patients with untreated metastatic pancreatic ductal adenocarcinoma. The study is open-label and randomized, aiming to extend progression-free survival compared to chemotherapy alone. Additionally, correlative studies will analyze tumor and blood samples to identify potential biomarkers that could personalize treatment strategies and provide insights into the antitumor mechanisms of the combination therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with histologically confirmed metastatic pancreatic ductal adenocarcinoma who have not received prior treatments.

Not a fit: Patients with prior treatments for pancreatic cancer or those with severe comorbidities affecting their performance status may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve treatment outcomes for patients with metastatic pancreatic cancer.

How similar studies have performed: While this approach is innovative, similar studies combining targeted therapies with chemotherapy have shown promise, suggesting potential for success.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent to study procedures and to correlative studies.
2. Histologically or cytologically proven metastatic PDAC.
3. No prior treatments (chemotherapy, radiation or surgery) for PDAC
4. Either sex aged ≥ 18 years.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 at study entry.
6. Imaging-documented measurable disease, according to RECIST 1.1 criteria.
7. Known dihydropyrimidine dehydrogenase (DPD) activity is mandatory for patients enrolled in PAXG scheme.
8. Adequate bone marrow haematological function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L AND platelet count ≥ 100 x 109/L AND haemoglobin ≥ 9 g/dL.
9. Adequate liver function: total bilirubin ≤ 1.5 x upper limit of normal (ULN) or ≤ 2 in case of biliary stent) and aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 5 X ULN.
10. Adequate renal function: serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min in males and ≥50 mL/min in females (calculated according to Cockroft-Gault formula).

Exclusion Criteria:

1. Prior malignancy within one year. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
2. Prior chemotherapy or any other medical treatment for metastatic PDAC (previous adjuvant chemotherapy is allowed if terminated \> 6 months previously).
3. Patients who have had prior treatment with an HDAC inhibitor and patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid.
4. Current use of statins or fibrates or any medication for hypercholesterolemia for any time during the 3 months before the study.
5. Proven hypersensitivity to statins and to any component of the other medications used in the trial.
6. Major surgical intervention within 4 weeks prior to enrollment;
7. Pregnancy and breast-feeding.
8. Brain metastasis.
9. Hepatitis or any severe liver disorder.
10. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol, or would interfere with the results of the study.
11. Patients with long QT-syndrome or QTc interval duration \> 480 msec or concomitant medication with drugs prolonging QTc (see list in the appendix).
12. History of poor co-operation, non-compliance with medical treatment, unreliability or any condition that may impair the patient's understanding of the Informed consent form.
13. Participation in any interventional drug or medical device study within 30 days prior to treatment start.
14. Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease.
15. Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study and until 6 months after the last trial treatment.

Where this trial is running

Naples, Italy and 4 other locations

• Istituto Nazionale Tumori di Napoli - IRCCS - Fondazione G. Pascale — Naples, Italy, Italy (Recruiting)
• Università vita e Salute, IRCCS San Raffaele — Milan, Milano, Italy (Recruiting)
• Università Cattolica Del Sacro Cuore, IRCCS Fondazione Policlinico Universitario Gemelli - Medical Oncology, Roma, Italia — Roma, Roma, Italy (Recruiting)
• University of Verona Hospital Trust — Verona, Verona, Italy (Recruiting)
• Ramon y Cajal Hospital and Health Research Institute (IRYCIS) — Madrid, Madrid, Spain (Recruiting)

Study contacts

• Principal investigator: Alfredo Budillon — IRCCS I.N.T. "G. Pascale
• Study coordinator: Antonio Avallone

Conditions Adenocarcinoma of the Pancreas; Metastatic