Nelfinavir, Radiation Therapy, Cisplatin, and Etoposide in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
Recruitment status was Recruiting
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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 Genetic: protein expression analysis Other: immunohistochemistry staining method Other: laboratory biomarker analysis Procedure: biopsy Radiation: radiation therapy |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Masking: Open Label Primary Purpose: Treatment |
| 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 |
- Dose-limiting toxicity as measured by NCI Common Toxicity Criteria [ Designated as safety issue: Yes ]
- Maximum tolerated dose and recommended phase II dose of nelfinavir mesylate [ Designated as safety issue: Yes ]
- Response at 3 months after completion of treatment as measured by RECIST criteria [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Expression of molecular markers (total Akt and p-Akt) in primary tumor or pathologic lymph nodes and in peripheral blood lymphocytes [ Designated as safety issue: No ]
| Estimated Enrollment: | 42 |
| Study Start Date: | June 2007 |
| Estimated Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
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 |
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| 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 | |
| Study Chair: | Ramesh Rengan, MD, PhD | Abramson Cancer Center of the University of Pennsylvania |
More Information
Additional Information:
No publications provided
| Responsible Party: | Ramesh Rengan, Abramson Cancer Center of the University of Pennsylvania |
| ClinicalTrials.gov Identifier: | NCT00589056 History of Changes |
| Other Study ID Numbers: | CDR0000582319, UPCC-806285, UPCC-04507 |
| Study First Received: | December 25, 2007 |
| Last Updated: | June 3, 2009 |
| 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 |
Additional relevant MeSH terms:
|
Carcinoma, Non-Small-Cell Lung Lung Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Etoposide phosphate Cisplatin Etoposide Protease Inhibitors |
Nelfinavir Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Antineoplastic Agents, Phytogenic Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action HIV Protease Inhibitors Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents |
ClinicalTrials.gov processed this record on May 21, 2013