Nelfinavir, Radiation Therapy, Cisplatin, and Etoposide in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery - Full Text View

Sponsors and Collaborators:	University of Pennsylvania National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00589056

Purpose

RATIONALE: Nelfinavir may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells. Nelfinavir may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving nelfinavir together with radiation therapy, cisplatin, and etoposide may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of nelfinavir when given together with radiation therapy, cisplatin, and etoposide and to see how well they work in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery.

Condition	Intervention	Phase
Lung Cancer	Drug: cisplatin Drug: etoposide Drug: nelfinavir mesylate Procedure: biopsy Procedure: immunohistochemistry staining method Procedure: laboratory biomarker analysis Procedure: protein expression analysis Procedure: radiation therapy	Phase I Phase II

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Etoposide Cisplatin Nelfinavir Nelfinavir Mesylate Etoposide phosphate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase I/II Trial of Protease Inhibitor, Nelfinavir, Given With Concurrent Thoracic Chemoradiotherapy in Patients With Locally-Advanced Non-Small Cell Lung Cancer

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

Primary Outcome Measures:

Dose-limiting toxicity as measured by NCI Common Toxicity Criteria
Maximum tolerated dose and recommended phase II dose of nelfinavir mesylate

Secondary Outcome Measures:

Response at 3 months after completion of treatment as measured by RECIST criteria
Overall survival
Expression of molecular markers (total Akt and p-Akt) in primary tumor or pathologic lymph nodes and in peripheral blood lymphocytes

Estimated Enrollment:	42
Study Start Date:	June 2007
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To determine the dose-limiting toxicities, maximum tolerated dose, and recommended phase II dose of nelfinavir mesylate when administered in combination with concurrent thoracic radiotherapy, cisplatin, and etoposide in patients with unresectable locally advanced non-small cell lung cancer.

Secondary

To determine the tumor response at 3 months after completion of treatment as measured by RECIST criteria.
To assess the inhibition of p-Akt in primary tumor or pathologic lymph nodes and in peripheral blood lymphocytes after 5-10 days of treatment with nelfinavir mesylate.
To determine the median overall survival (OS) of patients treated with this regimen.
To compare the observed median OS of these patients with the historical median OS of 17 months.

OUTLINE: This is a phase I, dose-escalation study of nelfinavir mesylate followed by a phase II study.

Phase I: Patients receive oral nelfinavir mesylate twice daily beginning 1-2 weeks before the initiation of chemoradiotherapy and continuing until the completion of radiotherapy. Patients undergo thoracic radiotherapy once daily 5 days a week for 7-8 weeks. Patients also receive cisplatin IV on days 1, 8, 29, and 36 and etoposide IV on days 1-5 and 29-33. After completion of chemoradiotherapy, patients receive two additional courses of cisplatin and etoposide.
Phase II: Patients receive nelfinavir mesylate at the maximum tolerated dose determined in phase I and concurrent chemoradiotherapy as in phase I.

Patients undergo blood sample collection periodically for correlative laboratory studies. Patients treated in the phase II portion of the study and those with primary tumors or pathologic lymph nodes easily accessible by core biopsy or mediastinoscopy also undergo tumor tissue biopsies. Blood and tumor tissue samples are analyzed for expression of molecular markers (total Akt and p-Akt ) by immunohistochemistry. The molecular markers are correlated with treatment response.

After completion of study treatment, patients are followed at 3, 6, and 12 months.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed non-small cell lung cancer
- Locally advanced (stage III) disease
- Unresectable disease
Candidate for concurrent definitive chemotherapy and thoracic radiotherapy, as determined by the treating physician
No malignant pleural effusion

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Absolute neutrophil count > 1,500/mm³
Platelet count > 100,000/mm³
Bilirubin ≤ 1.5 mg/dL
AST or ALT ≤ 2 times upper limit of normal (ULN)
Creatinine ≤ 1.5 times ULN
FEV_1 > 600 cc
Not pregnant or nursing
Negative pregnancy test
No weight loss > 10% within the past 6 months
No known HIV disease

PRIOR CONCURRENT THERAPY:

No prior thoracic radiotherapy
No prior HIV protease inhibitors
More than 5 years since prior chemotherapy
At least 3 weeks since prior exploratory thoracotomy
No concurrent medications that would preclude nelfinavir administration, including any of the following:
- Amiodarone
- Quinidine
- Rifampin
- Dihydroergotamine
- Ergonovine
- Ergotamine
- Methylergonovine
- Hypericum perforatum (St. John's wort)
- Lovastatin
- Simvastatin
- Pimozide
- Midazolam
- Triazolam

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589056

Locations

United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania	Recruiting
Philadelphia, Pennsylvania, United States, 19104-4283
Contact: Clinical Trials Office - Abramson Cancer Center of the Univers 800-474-9892

Sponsors and Collaborators

University of Pennsylvania

National Cancer Institute (NCI)

Investigators

Study Chair:

Ramesh Rengan, MD, PhD

University of Pennsylvania

More Information

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

Study ID Numbers:	CDR0000582319, UPCC-806285, UPCC-04507
Study First Received:	December 25, 2007
Last Updated:	September 22, 2008
ClinicalTrials.gov Identifier:	NCT00589056
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
recurrent non-small cell lung cancer

Study placed in the following topic categories:

Thoracic Neoplasms
Non-small cell lung cancer
Etoposide phosphate
Recurrence
Carcinoma
Respiratory Tract Diseases
Cisplatin

Lung Neoplasms
Lung Diseases
Nelfinavir
Carcinoma, Non-Small-Cell Lung
Etoposide
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Anti-Infective Agents
Respiratory Tract Neoplasms
HIV Protease Inhibitors
Anti-HIV Agents
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Enzyme Inhibitors

Antiviral Agents
Pharmacologic Actions
Protease Inhibitors
Neoplasms
Neoplasms by Site
Anti-Retroviral Agents
Radiation-Sensitizing Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on January 16, 2009