Nelfinavir, Radiation Therapy, Cisplatin, and Etoposide in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
| Status: | Recruiting |
|---|---|
| Conditions: | Lung Cancer, Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 4/2/2016 |
| Start Date: | June 2007 |
A Phase I/II Trial of Protease Inhibitor, Nelfinavir, Given With Concurrent Thoracic Chemoradiotherapy in Patients With Locally-Advanced Non-Small Cell Lung Cancer
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.
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.
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.
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.
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
We found this trial at
1
site
3400 Civic Center Blvd
Philadelphia, Pennsylvania 19104
Philadelphia, Pennsylvania 19104
(215) 662-6065
Abramson Cancer Center of the University of Pennsylvania The Abramson Cancer Center of the University...
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