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)
- Conditions
- Metastatic pancreatic ductal adenocarcinoma (mPDAC)
- Registration Number
- 2024-518710-11-00
- Brief Summary
To test whether the combination of valproic acid and simvastatin plus gemcitabine/nabpaclitaxel- based regimens (AG or PAXG) may improve the efficacy of first-line gemcitabine and nab-paclitaxel-based regimens in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).
- Detailed Description
The study hypothesizes that valproic acid (VPA) in combination with simvastatin (SIM) may improve the efficacy of first-line gemcitabine and nab-paclitaxel-based regimens and extend progression free survival (PFS) as compared with chemotherapy alone, in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).
Correlative studies on tumor and blood samples could identify potential biomarkers of toxicity and efficacy helping to define personalized treatment strategy and adding new insight into the antitumor mechanism of the combination approach.
Recruitment & Eligibility
- Status
- Ongoing, recruiting
- Sex
- Not specified
- Target Recruitment
- 240
Written informed consent to study procedures and to correlative studies.
Histologically or cytologically proven metastatic PDAC
No prior treatments (chemotherapy, radiation or surgery) for mPDAC
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 at study entry.
Imaging-documented measurable disease, according to RECIST 1.1 criteria.
Either sex aged ≥ 18
Known dihydropyrimidine dehydrogenase (DPD) activity is mandatory for patients enrolled in PAXG scheme
Adequate bone marrow haematological function: absolute neutrophil count (!NC) ≥ 1/5 x 109/L AND platelet count ≥ 100 x 109/L !ND haemoglobin ≥ 9 g/dL
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 (!LT) ≤ 5 X ULN/ 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).
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.
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.
Patients with long QT-syndrome or QTc interval duration > 480 msec or concomitant medication with drugs prolonging QTc
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
Participation in any interventional drug study within 30 days prior to treatment start.
Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease
Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study and until 6 months after the last trial treatment.
Prior chemotherapy or any other medical treatment for metastatic PDAC (previous adjuvant chemotherapy is allowed if terminated > 6 months previously).
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.
Current use of statins or fibrates or any medication for hypercholesterolemia for any time during the 3 months before the study.
Proven hypersensitivity to statins and to any component of the other medications used in the trial.
Major surgical intervention within 4 weeks prior to enrollment.
Pregnancy and breast-feeding.
Brain metastasis
Hepatitis or any severe liver disorder
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) between two arms PFS is defined as the time from randomization to the first documentation of objective disease progression by RECIST 1.1 criteria, or death due to any cause, whichever occurs first. PFS will be censored at the time of the last available tumor assessment documenting absence of progressive disease for patients alive at the time of analysis. Progression Free Survival (PFS) between two arms PFS is defined as the time from randomization to the first documentation of objective disease progression by RECIST 1.1 criteria, or death due to any cause, whichever occurs first. PFS will be censored at the time of the last available tumor assessment documenting absence of progressive disease for patients alive at the time of analysis.
- Secondary Outcome Measures
Name Time Method To compare the two arms in terms of: • Objective Tumor Response Rate (ORR) • Disease Control Rate (DCR) • Duration of Objective response (DOR) • CA19.9 level reduction • Overall survival (OS) • Overall toxicity rate • Quality of life (QoL) To compare the two arms in terms of: • Objective Tumor Response Rate (ORR) • Disease Control Rate (DCR) • Duration of Objective response (DOR) • CA19.9 level reduction • Overall survival (OS) • Overall toxicity rate • Quality of life (QoL)
To evaluate mechanistically–based pharmacokinetic and pharmacodynamic biomarkers on blood samples. To evaluate mechanistically–based pharmacokinetic and pharmacodynamic biomarkers on blood samples.
To explore prognostic factors and predictive biomarkers for response and toxicity on blood samples as well as primary tumors and resected metastases when available To explore prognostic factors and predictive biomarkers for response and toxicity on blood samples as well as primary tumors and resected metastases when available
Trial Locations
- Locations (12)
IRCCS Istituto Nazionale Tumori Fondazione Pascale
🇮🇹Naples, Italy
Azienda Ospedaliera Universitaria Integrata Verona
🇮🇹Verona, Italy
Ospedale Vito Fazzi Lecce
🇮🇹Lecce, Italy
IRCCS - Ospedale San Raffaele
🇮🇹Milano, Italy
Pia Fondazione Di Culto E Religione Card G Panico
🇮🇹Tricase, Italy
Azienda Ospedaliero Universitaria Ospedali Riuniti
🇮🇹Foggia, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Rome, Italy
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
Hospital Universitario Ramón y Cajal
🇪🇸Madrid, Spain
Hospital Universitario De Toledo
🇪🇸Toledo, Spain
Scroll for more (2 remaining)IRCCS Istituto Nazionale Tumori Fondazione Pascale🇮🇹Naples, ItalyAntonio AvalloneSite contact+390815903629a.avallone@istitutotumori.na.it