Phase I Study of Nelfinavir Mesylate in Patients With Metastatic, Refractory, or Recurrent Solid Tumors

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Alternate Title

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

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IBiomarker/Laboratory analysis, TreatmentClosed18 and overNCINCI-07-C-0047
NCI-P6880, NCT00436735

Special Category: NIH Clinical Center trial



  1. Determine the safety and toxicity of nelfinavir mesylate in patients with metastatic, refractory, or recurrent solid tumors.
  2. Determine the maximum tolerated dose of this drug in these patients.


  1. Determine the pharmacokinetics of this drug in these patients.
  2. Correlate cytochrome p450 3A4 (CYP3A4) activity with nelfinavir mesylate levels in these patients.
  3. Determine, preliminarily, the clinical efficacy of this drug in these patients.
  4. Assess the biological and clinical effects of this drug at the cellular and molecular level in these patients.

Entry 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

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

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

Expected Enrollment


A total of 45 patients will be accrued for this study.


Primary Outcome(s)

Safety and toxicity
Maximum tolerated dose

Secondary Outcome(s)

Correlation of CYP3A4 activity with nelfinavir mesylate levels
Clinical efficacy
Biological and clinical effects of nelfinavir mesylate at the cellular and molecular level


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.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

Phillip Dennis, MD, PhD, Principal investigator
Ph: 301-496-0929

Related Information

Web site for additional information

Registry Information

Official TitleA Phase I Trial of Nelfinavir (Viracept®) in Adults with Solid Tumors
Trial Start Date2006-09-01
Trial Completion Date2009-01-31 (estimated)
Registered in ClinicalTrials.govNCT00436735
Date Submitted to PDQ2007-01-04
Information Last Verified2008-12-07

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.