NCT00246103

Phase I Trial of Valproic Acid and Epirubicin in Solid Tumor Malignancies

Completed Phase 1 Last updated 20 February 2017

What this trial tests

Phase 1 trial testing Valproic acid in Neoplasms, Advanced in 82 participants. Completed in 1 April 2008.

Timeline

1 March 2004

Primary endpoint
1 April 2008

1 April 2008

Quick facts

Lead sponsor	H. Lee Moffitt Cancer Center and Research Institute
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	82
Start date	1 March 2004
Primary completion	1 April 2008
Estimated completion	1 April 2008
Sites	1 location across United States

Drugs / interventions tested

• Valproic acid (valproic acid) — full drug profile →
• Epirubicin (EPIRUBICIN) — full drug profile →
• 5-fluorouracil
• Cyclophosphamide.

Conditions studied

• Neoplasms, Advanced — all drugs for Neoplasms, Advanced →

Sponsor

H. Lee Moffitt Cancer Center and Research Institute

Who can join

18 and older, any sex, with Neoplasms, Advanced. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Maximum Tolerated Dose (MTD)
  Time frame: Up to 2 months
  MTD of Valproic acid in combination with Epirubicin. The maximum tolerated dose (MTD) will be defined as the highest dose level at which less than 2 out of 6 patients (\<33%) experience DLT in Cycle 1. A dose limiting toxicity (DLT) will be defined as any one of the specific adverse events (AEs) outlined in the protocol, occurring during Cycle 1 when considered related to therapy that is part of t

Sponsor's own description

This is a Phase I dose escalation trial with escalating doses of Valproic acid and one dose escalation step of epirubicin. VPA will be escalated starting at a dose that is recommended for use as an anti-convulsant or to treat migraine headaches. Epirubicin will be given by infusion on day 3 after the last dose of divalproex. The study will determine the highest dose that these two drugs can be given together and as part of a multidrug regimen with 5-fluorouracil and cyclophosphamide.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Combination Therapy With Histone Deacetylase Inhibitors (HDACi) for the Treatment of Cancer: Achieving the Full Therapeutic Potential of HDACi.
   Suraweera A, O'Byrne KJ, Richard DJ. · · 2018 · cited 496× · PMID 29651407 · DOI 10.3389/fonc.2018.00092
2. Inhibition of BET Proteins and Histone Deacetylase (HDACs): Crossing Roads in Cancer Therapy.
   Manzotti G, Ciarrocchi A, Sancisi V. · · 2019 · cited 60× · PMID 30841549 · DOI 10.3390/cancers11030304
3. HDAC Inhibitors: Dissecting Mechanisms of Action to Counter Tumor Heterogeneity.
   Karagiannis D, Rampias T. · · 2021 · cited 58× · PMID 34298787 · DOI 10.3390/cancers13143575
4. HDAC2 as a target for developing anti-cancer drugs.
   Jo H, Shim K, Kim HU, Jung HS, et al · · 2023 · cited 45× · PMID 36968022 · DOI 10.1016/j.csbj.2023.03.016
5. Revisiting Histone Deacetylases in Human Tumorigenesis: The Paradigm of Urothelial Bladder Cancer.
   Giannopoulou AF, Velentzas AD, Konstantakou EG, Avgeris M, et al · · 2019 · cited 40× · PMID 30875794 · DOI 10.3390/ijms20061291
6. The Role of HDACs in the Response of Cancer Cells to Cellular Stress and the Potential for Therapeutic Intervention.
   Alseksek RK, Ramadan WS, Saleh E, El-Awady R. · · 2022 · cited 32× · PMID 35897717 · DOI 10.3390/ijms23158141
7. Histone modification and histone modification-targeted anti-cancer drugs in breast cancer: Fundamentals and beyond.
   Feng J, Meng X. · · 2022 · cited 21× · PMID 36188615 · DOI 10.3389/fphar.2022.946811
8. Epigenetic Approaches to Overcome Fluoropyrimidines Resistance in Solid Tumors.
   Grumetti L, Lombardi R, Iannelli F, Pucci B, et al · · 2022 · cited 10× · PMID 35158962 · DOI 10.3390/cancers14030695