Spots Global Cancer Trial Database for Phase I Trial of Valproic Acid and Epirubicin in Solid Tumor Malignancies

The following info and data is provided "as is" to help patients around the globe.
We do not endorse or review these studies in any way.

Trial Identification

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

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

Study ID: NCT00246103

Conditions

Neoplasms, Advanced

Interventions

Study Description

Brief Summary: 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.

Detailed 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. Recommended concentrations for seizure control is 15-60 mg/kg. Pharmacokinetic studies from healthy volunteers and patients suggested a linear increase in plasma concentrations. A daily dosing of 16 mg/kg divalproex (delayed-release VPA) resulted in a peak VPA plasma concentration of 127 μg/ml (\~0.9 mM) 27. The recommended Phase II dose of VPA was 60 mg/kg/d when given by a one-hour intravenous infusion twice daily for 5 days every three weeks. Synergistic activity between VPA and epirubicin has been observed at 0.5 mM of VPA in our preclinical laboratory studies. Patients will receive an intravenous loading dose of VPA followed by divalproex in two daily doses for 5 doses. The loading dose of VPA will avoid a delay in peak plasma concentrations and excessive nausea. Epirubicin will be given by infusion on day 3 after the last dose of divalproex. Once the MTD for this two drug regimen has been determined, the maximum tolerated dose will be determined as part of the FEC regimen (5-fluorouracil, epirubicin and cyclophosphamide).