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

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00589056
• Other study ID #: UPCC 04507
• Secondary ID: IRB-806285CDR000
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 2007
• Est. completion date: March 2012

Study information

• Verified date: April 2020
• Source: Abramson Cancer Center of the University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: March 2012
• Est. primary completion date: March 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• cisplatin

• etoposide

• nelfinavir mesylate

Genetic:
• protein expression analysis

Other:
• immunohistochemistry staining method

• laboratory biomarker analysis

Procedure:
• biopsy

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Abramson Cancer Center of the University of Pennsylvania	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting Toxicity	Any grade III or higher toxicity during chemoradiation, per CTCAE	90 days
Primary	Maximum Tolerated Dose of Nelfinavir	As determined by dose escalation rules	90 days
Secondary	Clinical Response of Tumor	Tumor size as determined by imaging	90 days

External Links

•   Clinical trial summary from the National Cancer Institute's PDQ® database