Valproic acid for Metastatic pancreatic ductal adenocarcinoma

Inclusion criteria

• {"criterion_text":"- Written informed consent to study procedures and to correlative studies.\n- Histologically or cytologically proven metastatic PDAC\n- No prior treatments (chemotherapy, radiation or surgery) for mPDAC\n- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1 at study entry.\n- Imaging-documented measurable disease, according to RECIST 1.1 criteria.\n- Either sex aged ≥ 18\n- Known dihydropyrimidine dehydrogenase (DPD) activity is mandatory for patients enrolled in PAXG scheme\n- 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\n- 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)."}

Exclusion criteria

• {"criterion_text":"- 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.\n- 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.\n- Patients with long QT-syndrome or QTc interval duration > 480 msec or concomitant medication with drugs prolonging QTc\n- 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\n- Participation in any interventional drug study within 30 days prior to treatment start.\n- Patients who cannot take oral medication, who require intravenous alimentation, have had prior surgical procedures affecting absorption, or have active peptic ulcer disease\n- Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study and until 6 months after the last trial treatment.\n- Prior chemotherapy or any other medical treatment for metastatic PDAC (previous adjuvant chemotherapy is allowed if terminated > 6 months previously).\n- 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.\n- Current use of statins or fibrates or any medication for hypercholesterolemia for any time during the 3 months before the study.\n- Proven hypersensitivity to statins and to any component of the other medications used in the trial.\n- Major surgical intervention within 4 weeks prior to enrollment.\n- Pregnancy and breast-feeding.\n- Brain metastasis\n- Hepatitis or any severe liver disorder"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"PFS defined as time from randomization to first documentation of objective disease progression by RECIST 1.1, or death from any cause; censoring at last tumor assessment if alive without progression."}

Secondary endpoints

• {"endpoint_text":"- 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)","definition_or_measurement_approach":"Comparative measures between arms: ORR, DCR, DOR (per RECIST), CA19.9 level changes, OS, overall toxicity (safety reporting), and QoL (questionnaires such as EORTC QLQ-C30/PAN26 referenced in documents)."}
• {"endpoint_text":"- To evaluate mechanistically–based pharmacokinetic and pharmacodynamic biomarkers on blood samples.","definition_or_measurement_approach":"Measurement of PK/PD biomarkers on blood samples as per correlative study procedures (blood sampling and biomarker assays described as secondary endpoints)."}
• {"endpoint_text":"- To explore prognostic factors and predictive biomarkers for response and toxicity on blood samples as well as primary tumors and resected metastases when available","definition_or_measurement_approach":"Correlative/translational analyses on blood and tumor tissue to identify prognostic and predictive biomarkers for response and toxicity."}

Italy

Earliest CTIS Part Ii Submission Date

28-10-2024

Latest Decision Or Authorization Date

17-12-2025

Processing Time Days

415

Number Of Sites

9

Number Of Participants

150

Spain

Earliest CTIS Part Ii Submission Date

28-10-2024

Latest Decision Or Authorization Date

08-01-2026

Processing Time Days

437

Number Of Sites

5

Number Of Participants

20

Primary sponsor

Full Name

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy