Nelfinavir in Treating Patients With Metastatic, Refractory, or Recurrent Solid Tumors - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00436735

Purpose

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 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 Other: pharmacological study	Phase I

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Carcinoid Tumors Colorectal Cancer Head and Neck Cancer Lung Cancer Ovarian Cancer Pheochromocytoma Soft Tissue Sarcoma

Drug Information available for: Midazolam Midazolam maleate Midazolam hydrochloride Nelfinavir Nelfinavir Mesylate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

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
Estimated Primary Completion Date:	January 2009 (Final data collection date for primary outcome measure)

Detailed 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.

Eligibility

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

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00436735

Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office	Recruiting
Bethesda, Maryland, United States, 20892-1182
Contact: Clinical Trials Office - Warren Grant Magnusen Clinical Center 888-NCI-1937

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Phillip Dennis, MD, PhD

National Cancer Institute (NCI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Web site for additional information This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000529905, NCI-07-C-0047, NCI-P6880
Study First Received:	February 15, 2007
Last Updated:	May 13, 2009
ClinicalTrials.gov Identifier:	NCT00436735 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Thoracic Neoplasms
Anti-Infective Agents
Neurotransmitter Agents
Carcinoma, Basosquamous
Rectal Neoplasms
Thyroid Cancer, Papillary
Pancreatic Neoplasms
Thyroid Cancer, Medullary
Colonic Diseases
Anesthetics
Urogenital Neoplasms
Rectal Diseases
Neoplasms, Connective and Soft Tissue
Thyroid Cancer, Follicular
Lung Neoplasms

Neoplasm Metastasis
Neuroepithelioma
Ovarian Cancer
Neoplasms, Basal Cell
Nelfinavir
Endocrine Gland Neoplasms
Carcinoid Syndrome
HIV Protease Inhibitors
Anti-HIV Agents
Tranquilizing Agents
Digestive System Neoplasms
Carcinoma, Islet Cell
Adjuvants, Immunologic
Genital Neoplasms, Female
Endocrine System Diseases

Additional relevant MeSH terms:

Thoracic Neoplasms
Anti-Infective Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Carcinoma, Basosquamous
Pancreatic Neoplasms
Physiological Effects of Drugs
Colonic Diseases
Anesthetics
Urogenital Neoplasms
Rectal Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Site
Pathologic Processes
Lung Neoplasms

Therapeutic Uses
Neoplasm Metastasis
Neoplasms, Basal Cell
Nelfinavir
Endocrine Gland Neoplasms
HIV Protease Inhibitors
Anti-HIV Agents
Tranquilizing Agents
Digestive System Neoplasms
Genital Neoplasms, Female
Endocrine System Diseases
Carcinoma, Basal Cell
Adenoma, Islet Cell
Malignant Carcinoid Syndrome
Protease Inhibitors

ClinicalTrials.gov processed this record on September 03, 2009