A Phase I Trial of Nelfinavir (Viracept®) in Adults With Solid Tumors
- Determine the safety and toxicity of nelfinavir mesylate in patients with metastatic,
refractory, or recurrent solid tumors.
- Determine the maximum tolerated dose of this drug in these patients.
- Determine the pharmacokinetics of this drug in these patients.
- Correlate cytochrome p450 3A4 (CYP3A4) activity with nelfinavir mesylate levels in
- Determine, preliminarily, the clinical efficacy of this drug in these patients.
- Assess the biological and clinical effects of this drug at the cellular and molecular
level in these patients.
OUTLINE: This is a dose-escalation study.
Patients receive oral nelfinavir mesylate twice daily on days 1-21. Treatment repeats every
21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Patients with responding disease may continue to receive nelfinavir mesylate.
Cohorts of 3-6 patients receive escalating doses of nelfinavir mesylate until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients receive oral midazolam hydrochloride on days -2 and 20 and then undergo blood
collection on days -2 and 20 for midazolam pharmacokinetics to determine CYP3A4 activity.
Nelfinavir mesylate pharmacokinetics are performed on day 1 of courses 1 and 2. Patients
also undergo blood collection on days 1, 8, and 42 for biological marker laboratory studies,
including vascular endothelial growth factor and basic fibroblast growth factor levels as
measured by enzyme-linked immunosorbent assay and phospho-Akt, total Akt, cleaved Parp,
Beclin 1, p-eIF2α, LC-3, and other signal transduction markers as measured by Western blot.
After completion of study treatment, patients are followed for 4 weeks.
PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.
Primary Purpose: Treatment
Safety and toxicity
Phillip Dennis, MD, PhD
National Cancer Institute (NCI)
United States: Federal Government
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|