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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
Est. completion date
Est. primary completion date
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
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