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A Phase I Trial of Nelfinavir (Viracept®) in Adults With Solid Tumors

Phase 1
18 Years
Open (Enrolling)
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

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Trial Information

A Phase I Trial of Nelfinavir (Viracept®) in Adults With Solid Tumors



- 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.

Inclusion Criteria


- Histologically confirmed* solid malignancy for which there is no known curative

- 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

- 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,

- 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

Type of Study:


Study Design:

Primary Purpose: Treatment

Outcome Measure:

Safety and toxicity

Safety Issue:


Principal Investigator

Phillip Dennis, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)


United States: Federal Government

Study ID:

070047, CDR0000529905



Start Date:

September 2006

Completion Date:

Related Keywords:

  • 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
  • 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
  • Carcinoid Tumor
  • Carcinoma
  • Carcinoma, Merkel Cell
  • Colorectal Neoplasms
  • Head and Neck Neoplasms
  • Lung Neoplasms
  • Neoplasm Metastasis
  • Neoplasms
  • Neoplasms, Second Primary
  • Ovarian Neoplasms
  • Pheochromocytoma
  • Carcinoma, Neuroendocrine
  • Malignant Carcinoid Syndrome
  • Gastrointestinal Neoplasms
  • Adenoma, Islet Cell
  • Skin Neoplasms
  • Carcinoma, Basal Cell
  • Carcinoma, Basosquamous
  • Carcinoma, Squamous Cell
  • Sarcoma



Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office Bethesda, Maryland  20892-1182