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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by National Institutes of Health Clinical Center (CC).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00436735
First received: February 15, 2007
Last updated: September 29, 2011
Last verified: September 2011

February 15, 2007
September 29, 2011
September 2006
Not Provided
  • Safety and toxicity [ Designated as safety issue: Yes ]
  • Maximum tolerated dose [ Designated as safety issue: Yes ]
  • Safety and toxicity
  • Maximum tolerated dose
Complete list of historical versions of study NCT00436735 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Pharmacokinetics
  • Correlation of CYP3A4 activity with nelfinavir mesylate levels
  • Evidence of clinical efficacy
  • Biological and clinical effects at the cellular and molecular level
Not Provided
Not Provided
 
Nelfinavir in Treating Patients With Metastatic, Refractory, or Recurrent Solid Tumors
A Phase I Trial of Nelfinavir (Viracept®) in Adults With 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.

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.

Interventional
Phase 1
Primary Purpose: Treatment
  • 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
  • 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
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
45
Not Provided
Not Provided

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00436735
070047, CDR0000529905, NCI-07-C-0047, NCI-P6880
Not Provided
Not Provided
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Phillip Dennis, MD, PhD National Cancer Institute (NCI)
National Institutes of Health Clinical Center (CC)
September 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP