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

Descriptive Information
Brief Title † Nelfinavir in Treating Patients With Metastatic, Refractory, or Recurrent Solid Tumors
Official Title † A Phase I Trial of Nelfinavir (Viracept®) in Adults With Solid Tumors
Brief 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.
Detailed 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 Phase Phase 1
Study Type † Interventional
Study Design † Primary Purpose: Treatment
Primary Outcome Measure † Safety and toxicity
Secondary Outcome Measure † Pharmacokinetics
Condition † Colorectal Cancer Gastrointestinal Carcinoid Tumor Head and Neck Cancer Islet Cell Tumor Lung Cancer Metastatic Cancer Neuroendocrine Carcinoma of the Skin Ovarian Cancer Pheochromocytoma Sarcoma Unspecified Adult Solid Tumor, Protocol Specific
Intervention † Drugmidazolam hydrochloride
Study Arms / Comparison Groups
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 45
Start Date † September 2006
Completion Date
Primary Completion Date
Eligibility Criteria † DISEASE CHARACTERISTICS: - Histologically confirmed* solid malignancy for which there is no known curative therapy - Relapsed disease OR failed to respond to standard therapy OR refused standard therapy in cases where no curative option exists NOTE: *An exception to histological confirmation will be allowed if no tissue is available for review, the presence of malignancy is documented in a pathology report from an outside institution, or a new biopsy is contraindicated because of safety. - Brain metastases allowed provided all of the following criteria are met: - Prior evaluation and appropriate counseling - Prior treatment by radiation oncology PATIENT CHARACTERISTICS: - ECOG performance status 0-2 - Life expectancy ≥ 3 months - Absolute neutrophil count ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - Bilirubin
Gender Both
Ages 18 Years - N/A
Accepts Healthy Volunteers No
Contacts ††
Location Countries † United States
Administrative Information
NCT ID † NCT00436735
Organization ID 070047, CDR0000529905
Secondary IDs †† NCI-07-C-0047, NCI-P6880
Responsible Party
Study Sponsor † National Cancer Institute (NCI)
Collaborators ††
Investigators † Principal Investigator: Phillip Dennis, MD, PhD, National Cancer Institute (NCI)
Information Provided By
Verification Date September 2011
First Received Date † February 15, 2007
Last Updated Date September 29, 2011
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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