Nelfinavir in Treating Patients With Metastatic, Refractory, or Recurrent Solid Tumors

Colorectal Cancer Clinical Trial

Official title: A Phase I Trial of Nelfinavir (Viracept®) in Adults With Solid Tumors

Status Active, not recruiting

Clinical Trial Summary

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.

Clinical Trial Description

OBJECTIVES:

Primary

• 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.

Secondary

• 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. ;

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoid Tumor
• Carcinoma, Merkel Cell
• Carcinoma, Neuroendocrine
• Colorectal Cancer
• Gastrointestinal Carcinoid Tumor
• Gastrointestinal Neoplasms
• Head and Neck Cancer
• Head and Neck Neoplasms
• Islet Cell Tumor
• Lung Cancer
• Malignant Carcinoid Syndrome
• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms
• Neuroendocrine Carcinoma of the Skin
• Neuroendocrine Tumors
• Ovarian Cancer
• Pheochromocytoma
• Sarcoma
• Skin Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific

• NCT number: NCT00436735
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: September 2006