Valproic Acid/Simvastatin Plus Gemcitabine/Nab-paclitaxel Based Regimens in Untreated Metastatic Pancreatic Adenocarcinoma Patients

RECRUITING

NCT05821556

PHASE2

Sponsor: National Cancer Institute, Naples

Summary

This is a proof-of-concept, Open label, randomized, multicentric, superiority phase-2 study.

Official title: 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).

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

240

Start Date

2023-06-12

Completion Date

2026-06

Last Updated

2025-07-29

Healthy Volunteers

No

Conditions

Adenocarcinoma of the Pancreas

Interventions

DRUG

Valproic acid

The treatment should be started within 3 days from randomization. One cycle consisted of 28 days of treatment for both arms. Patients will continue to receive study treatment up to 6 cycles until disease progression, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria. Continuation of treatment, over the six cycles, will be allowed only in case of clinical benefit, defined as continuous decrease of CA19-9 concentration or radiological response, without unacceptable toxicity. All subjects who finish treatment, whichever the reason, will enter in the follow-up. We expect that for the primary endpoint, PFS, follow-up will last up to 10 months after enrollment. Anyhow, all subjects will be followed until death and data on subsequent treatment will be collected.

DRUG

Simvastatin 20mg

The treatment should be started within 3 days from randomization. One cycle consisted of 28 days of treatment for both arms. Patients will continue to receive study treatment up to 6 cycles until disease progression, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria. Continuation of treatment, over the six cycles, will be allowed only in case of clinical benefit, defined as continuous decrease of CA19-9 concentration or radiological response, without unacceptable toxicity. All subjects who finish treatment, whichever the reason, will enter in the follow-up. We expect that for the primary endpoint, PFS, follow-up will last up to 10 months after enrollment. Anyhow, all subjects will be followed until death and data on subsequent treatment will be collected.

DRUG

Gemcitabine 1000 mg

The treatment should be started within 3 days from randomization. One cycle consisted of 28 days of treatment for both arms. Patients will continue to receive study treatment up to 6 cycles until disease progression, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria. Continuation of treatment, over the six cycles, will be allowed only in case of clinical benefit, defined as continuous decrease of CA19-9 concentration or radiological response, without unacceptable toxicity. All subjects who finish treatment, whichever the reason, will enter in the follow-up. We expect that for the primary endpoint, PFS, follow-up will last up to 10 months after enrollment. Anyhow, all subjects will be followed until death and data on subsequent treatment will be collected.

DRUG

Nab paclitaxel

The treatment should be started within 3 days from randomization. One cycle consisted of 28 days of treatment for both arms. Patients will continue to receive study treatment up to 6 cycles until disease progression, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria. Continuation of treatment, over the six cycles, will be allowed only in case of clinical benefit, defined as continuous decrease of CA19-9 concentration or radiological response, without unacceptable toxicity. All subjects who finish treatment, whichever the reason, will enter in the follow-up. We expect that for the primary endpoint, PFS, follow-up will last up to 10 months after enrollment. Anyhow, all subjects will be followed until death and data on subsequent treatment will be collected.

DRUG

Cisplatin

The treatment should be started within 3 days from randomization. One cycle consisted of 28 days of treatment for both arms. Patients will continue to receive study treatment up to 6 cycles until disease progression, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria. Continuation of treatment, over the six cycles, will be allowed only in case of clinical benefit, defined as continuous decrease of CA19-9 concentration or radiological response, without unacceptable toxicity. All subjects who finish treatment, whichever the reason, will enter in the follow-up. We expect that for the primary endpoint, PFS, follow-up will last up to 10 months after enrollment. Anyhow, all subjects will be followed until death and data on subsequent treatment will be collected.

DRUG

Capecitabine

The treatment should be started within 3 days from randomization. One cycle consisted of 28 days of treatment for both arms. Patients will continue to receive study treatment up to 6 cycles until disease progression, unacceptable toxicity, physician's decision, patient's refusal, or any other discontinuation criteria. Continuation of treatment, over the six cycles, will be allowed only in case of clinical benefit, defined as continuous decrease of CA19-9 concentration or radiological response, without unacceptable toxicity. All subjects who finish treatment, whichever the reason, will enter in the follow-up. We expect that for the primary endpoint, PFS, follow-up will last up to 10 months after enrollment. Anyhow, all subjects will be followed until death and data on subsequent treatment will be collected.

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.

Locations (5)

Istituto Nazionale Tumori di Napoli - IRCCS - Fondazione G. Pascale

Naples, Italy, Italy

Università vita e Salute, IRCCS San Raffaele

Milan, Milano, Italy

Università Cattolica Del Sacro Cuore, IRCCS Fondazione Policlinico Universitario Gemelli - Medical Oncology, Roma, Italia

Roma, Roma, Italy

University of Verona Hospital Trust

Verona, Verona, Italy

Ramon y Cajal Hospital and Health Research Institute (IRYCIS)

Madrid, Madrid, Spain

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