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

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• 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
• Email: a.avallone@istitutotumori.na.it
• Phone: 08117770357

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.