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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00436735
• Other study ID #: 070047, CDR0000529905
• Secondary ID: NCI-07-C-0047NCI
• Status: Active, not recruiting
• Phase: Phase 1
• First received: February 15, 2007
• Last updated: September 29, 2011
• Start date: September 2006

Study information

• Verified date: September 2011
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 45
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 < 1.5 times upper limit of normal (ULN)

• AST and ALT = 2.5 times ULN

• Creatinine < 1.5 times ULN

• Not nursing

• Negative pregnancy test

• Fertile patients must use effective barrier contraception

• No myocardial infarction within the past 6 months

• No uncontrolled intercurrent illness, including, but not limited to, any of the following:

• Ongoing or active infection

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situation that would preclude study compliance

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• More than 28 days since prior chemotherapy or biologic therapy

• No concurrent chemotherapy, biologic therapy, or radiotherapy

• No concurrent hormonal methods of birth control

• No concurrent CYP3A4 inhibitors, including any of the following:

• Antiarrhythmics (e.g., amiodarone, quinidine)

• Neuroleptics (e.g., pimozide)

• Sedative or hypnotic agents (e.g., midazolam hydrochloride, triazolam)

• Ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, methylergonovine)

• Hydroxymethyl glutaryl co-enzyme A (HMG-CoA) reductase inhibitors (e.g., lovastatin, simvastatin, atorvastatin)

• Concurrent pravastatin and rovustatin allowed

• Rifampin

• Rifabutin

• Felodipine

• Nifedipine

• Sildenafil

• Hypericum perforatum (St. John's wort)

• No other concurrent anticancer agents or therapies

• No concurrent escalating doses of corticosteroids for other noncancerous medical conditions

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

Intervention

Drug:
• midazolam hydrochloride

• nelfinavir mesylate

Genetic:
• gene expression analysis

• polymerase chain reaction

• protein expression analysis

Other:
• immunoenzyme technique

• immunologic technique

• laboratory biomarker analysis

• mass spectrometry

Locations

Country	Name	City	State
United States	Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and toxicity			Yes
Primary	Maximum tolerated dose			Yes
Secondary	Pharmacokinetics			No
Secondary	Correlation of CYP3A4 activity with nelfinavir mesylate levels			No
Secondary	Clinical efficacy			No
Secondary	Biological and clinical effects of nelfinavir mesylate at the cellular and molecular level			No