Nelfinavir in Treating Patients With Metastatic, Refractory, or Recurrent Solid Tumors
RATIONALE: Nelfinavir may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of nelfinavir in treating patients with metastatic, refractory, or recurrent solid tumors.
Gastrointestinal Carcinoid Tumor
Head and Neck Cancer
Islet Cell Tumor
Neuroendocrine Carcinoma of the Skin
Unspecified Adult Solid Tumor, Protocol Specific
Drug: midazolam hydrochloride
Drug: nelfinavir mesylate
Genetic: gene expression analysis
Genetic: polymerase chain reaction
Genetic: protein expression analysis
Other: immunoenzyme technique
Other: immunologic technique
Other: laboratory biomarker analysis
Other: mass spectrometry
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Phase I Trial of Nelfinavir (Viracept®) in Adults With Solid Tumors|
- Safety and toxicity [ Designated as safety issue: Yes ]
- Maximum tolerated dose [ Designated as safety issue: Yes ]
- Pharmacokinetics [ Designated as safety issue: No ]
- Correlation of CYP3A4 activity with nelfinavir mesylate levels [ Designated as safety issue: No ]
- Clinical efficacy [ Designated as safety issue: No ]
- Biological and clinical effects of nelfinavir mesylate at the cellular and molecular level [ Designated as safety issue: No ]
|Study Start Date:||September 2006|
- 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 these patients.
- 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.
|United States, Maryland|
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office|
|Bethesda, Maryland, United States, 20892-1182|
|Principal Investigator:||Phillip Dennis, MD, PhD||National Cancer Institute (NCI)|