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
Information provided by:
National Institutes of Health Clinical Center (CC) Identifier:
First received: February 15, 2007
Last updated: September 29, 2011
Last verified: September 2011

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.

Condition Intervention Phase
Colorectal Cancer
Gastrointestinal Carcinoid Tumor
Head and Neck Cancer
Islet Cell Tumor
Lung Cancer
Metastatic Cancer
Neuroendocrine Carcinoma of the Skin
Ovarian Cancer
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
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase I Trial of Nelfinavir (Viracept®) in Adults With Solid Tumors

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Safety and toxicity [ Designated as safety issue: Yes ]
  • Maximum tolerated dose [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 45
Study Start Date: September 2006
Detailed Description:



  • 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.


  • 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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00436735

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Phillip Dennis, MD, PhD National Cancer Institute (NCI)
  More Information

No publications provided Identifier: NCT00436735     History of Changes
Other Study ID Numbers: 070047, CDR0000529905  NCI-07-C-0047  NCI-P6880 
Study First Received: February 15, 2007
Last Updated: September 29, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
unspecified adult solid tumor, protocol specific
recurrent non-small cell lung cancer
recurrent small cell lung cancer
recurrent colon cancer
recurrent rectal cancer
recurrent adult soft tissue sarcoma
recurrent uterine sarcoma
ovarian sarcoma
recurrent gastrointestinal carcinoid tumor
pancreatic G-cell adenoma
pancreatic G-cell carcinoma
pancreatic alpha cell adenoma
pancreatic alpha cell carcinoma
pancreatic beta islet cell adenoma
pancreatic beta islet cell carcinoma
pancreatic delta cell adenoma
pancreatic delta cell carcinoma
recurrent islet cell carcinoma
recurrent neuroendocrine carcinoma of the skin
thyroid gland medullary carcinoma
recurrent pheochromocytoma
metastatic gastrointestinal carcinoid tumor
regional gastrointestinal carcinoid tumor
liver metastases
lung metastases
stage IV follicular thyroid cancer
stage IV papillary thyroid cancer
recurrent thyroid cancer
stage IV neuroendocrine carcinoma of the skin

Additional relevant MeSH terms:
Carcinoid Tumor
Carcinoma, Merkel Cell
Carcinoma, Neuroendocrine
Gastrointestinal Neoplasms
Head and Neck Neoplasms
Malignant Carcinoid Syndrome
Neoplasm Metastasis
Neuroendocrine Tumors
Skin Neoplasms
DNA Virus Infections
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplastic Processes
Neuroectodermal Tumors
Pathologic Processes
Polyomavirus Infections
Skin Diseases processed this record on February 11, 2016