Lung Cancer Clinical Trial
Neoadjuvant Chemoradiotherapy With or Without Gefitinib in Treating Patients With Stage IIIA or Stage IIIB Non-Small Cell Lung Cancer
Summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Biological therapies such as gefitinib may interfere with the growth of the tumor cells and slow the growth of the tumor. Combining chemotherapy and radiation therapy with gefitinib before surgery may shrink the tumor so that it can be removed during surgery.
PURPOSE: Phase I/II trial to compare the effectiveness of neoadjuvant chemoradiotherapy with or without gefitinib in treating patients who are undergoing surgery for stage III non-small cell lung cancer.
Full Description
OBJECTIVES: Phase I:
Determine the tolerability and toxicity of gefitinib in combination with chest radiotherapy in patients with stage IIIA or stage IIIB non-small cell lung cancer.
Phase II:
Compare the pathologic response (complete response and rate of downstaging) in patients treated with neoadjuvant chemoradiotherapy with vs without gefitinib.
Compare the feasibility and toxicity profile of these regimens in these patients.
Compare the resection rates, time to progression, and overall survival of patients treated with these regimens.
Correlate the percent decline in the fludeoxyglucose F 18 standardized uptake value as measured by position emission tomography with pathologic response at resection, time to progression, and overall survival in patients treated with these regimens.
OUTLINE:
Phase I: This is an open-label, nonrandomized study.
Induction: Patients receive cisplatin IV over 60 minutes on day 1 and gemcitabine IV over 30 minutes on days 1 and 8. Treatment repeats every 3 weeks for a total of 2 courses in the absence of disease progression or unacceptable toxicity.
Consolidation: Within 3-4 weeks after the completion of induction therapy, patients undergo radiotherapy once daily 5 days a week for 5 weeks and receive oral gefitinib once daily concurrently.
A cohort of 3-6 patients receives consolidation chemoradiotherapy. If 2 of 6 patients experience dose-limiting toxicity, gefitinib is deleted from consolidation therapy in phase II arm II.
Surgery: Patients without disease progression after consolidation therapy undergo thoracotomy within 3-5 weeks after consolidation.
Maintenance: Beginning 2-4 weeks after surgery, patients receive oral gefitinib once daily for 6 months in the absence of disease progression.
Phase II: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive induction and consolidation therapy (with the exception of gefitinib) as in phase I. Patients also receive docetaxel IV over 60 minutes concurrently with radiotherapy during consolidation. Patients undergo surgery as in phase I.
Arm II: Patients receive therapy (including gefitinib) as in phase I. Patients also receive docetaxel IV over 60 minutes concurrently with radiotherapy during consolidation.
Patients are followed every 6-8 weeks for the first 12 months and then every 4-6 months thereafter.
PROJECTED ACCRUAL: A total of 43-80 patients (3-6 patients for phase I and 40-74 patients [20-37 per treatment arm] for phase II) will be accrued for this study.
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed non-small cell lung cancer
Stage IIIA (T1-3, N2)
Positive (pathological) ipsilateral mediastinal node
Selective stage IIIB meeting all of the following criteria:
No pleural/pericardial effusion or superior vena cava syndrome
T4 due to invasion of carina, trachea, or mediastinal structures
Mediastinal N3 nodes (without supraclavicular or cervical adenopathy)
Proof of N2 or N3 status requires surgical staging of the mediastinum (mediastinoscopy, mediastinotomy, or exploration)
Expression of epidermal growth factor receptor (at least 1+) by immunohistochemistry
Measurable disease by contrast CT scan allowed
No bronchoalveolar cell carcinoma
No prior diagnosis of lung cancer
PATIENT CHARACTERISTICS:
Age
19 and over
Performance status
ECOG 0-1 (0-2 if albumin is at least 0.85 times lower limit of normal and weight loss within 3 months before diagnosis is no greater than 10%)
Life expectancy
Not specified
Hematopoietic
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 150,000/mm^3
Hemoglobin at least 10 g/dL
Hepatic
Bilirubin normal
AST and ALT no greater than 2.5 times upper limit of normal (ULN)
Alkaline phosphatase no greater than 2 times ULN
Alkaline phosphatase between 1.5-2 times ULN requires a negative bone scan for metastatic bone disease
Renal
Creatinine no greater than 1.4 mg/dL OR
Creatinine clearance at least 60 mL/min
Cardiac
No myocardial infarction within the past 3 months
No active angina
No unstable heart rhythms
No congestive heart failure
Pulmonary
Post-resection predicted FEV_1% greater than 35%
Predicted FEV_1% is defined as FEV_1% times percent perfusion to uninvolved lung from quantitative lung V/Q scan report
Other
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for at least 6 weeks after study treatment
No other uncontrolled medical illness
No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix
No grade 2 or greater peripheral neuropathy
No concurrent ocular inflammation or infection
No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
No known severe hypersensitivity reaction to gefitinib or any of its excipients
No prior severe allergic reaction to platinum-containing compounds or mannitol
PRIOR CONCURRENT THERAPY:
Biologic therapy
No concurrent growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF]) during chemotherapy
Chemotherapy
No prior chemotherapy for lung cancer
Endocrine therapy
Not specified
Radiotherapy
No prior radiotherapy for lung cancer
Surgery
Recovered from prior major surgery
No concurrent ophthalmic surgery
Other
More than 30 days since prior unapproved or investigational drugs
No concurrent use of the following drugs:
Phenytoin
Carbamazepine
Barbiturates
Rifampin
Phenobarbital
Hypericum perforatum (St. John's Wort)
Warfarin
No concurrent retinoids
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There is 1 Location for this study
Birmingham Alabama, 35294, United States
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