NCT00246103

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

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 82 (actual)
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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).

Conditions

• Neoplasms, Advanced

Interventions

Type	Name	Description
DRUG	Valproic acid	Beginning Dose, Level 1: 15 mg/kg/day.
DRUG	Epirubicin	Beginning Dose, Level 1: 75 mg/m\^2.
DRUG	5-fluorouracil	For breast cancer participants treated at MTD of Valproic acid and Epirubicin: 5-fluorouracil 500 mg/m\^2.
DRUG	Cyclophosphamide.	For breast cancer participants treated at MTD of Valproic acid and Epirubicin: cyclophosphamide 500 mg/m\^2.

Timeline

• Start date: 2004-03-01
• Primary completion: 2008-04-01
• Completion: 2008-04-01
• First posted: 2005-10-31
• Last updated: 2017-02-23

Locations

1 site across 1 country: United States