A Phase III Prospective Randomized, Double-Blind, Placebo-Controlled Trial of the Epidermal Growth Factor Receptor Antagonist, ZD1839 (IRESSA) in Completely Resected Primary Stage IB, II and IIIA Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 3
- Intervention
- gefitinib
- Conditions
- Adenocarcinoma of the Lung
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 503
- Locations
- 1
- Primary Endpoint
- Overall Survival
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
This randomized phase III trial studies how well gefitinib works in treating patients with stage IB, II, or IIIA non-small cell lung cancer that was completely removed by surgery. Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known if gefitinib may be an effective treatment in preventing tumors from returning after they have been removed by surgery.
Detailed Description
PRIMARY OBJECTIVES: I. To assess, in comparison with placebo, the impact of adjuvant therapy with two years of daily oral ZD1839 (IRESSA) (gefitinib) on the overall survival of patients with completely resected (T1N1-2, T2N0-2, T3N0-2) non-small cell lung cancer (NSCLC). SECONDARY OBJECTIVES: I. To compare the disease-free survival in the placebo arm to the ZD1839 (IRESSA) arm. II. To confirm the prognostic significance of epidermal growth factor receptor (EGFR) expression, phosphorylation and mutations when present in the primary tumor. III. To assess the ability of EGFR expression, phosphorylation and mutations in the primary tumor to predict the relative impact of ZD1839 (IRESSA) on survival. IV. To establish a comprehensive tumour bank linked to a clinical database for the further study of molecular markers in resected NSCLC. V. To further evaluate toxicity related to ZD1839 (IRESSA). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive gefitinib orally (PO) once daily (QD) for 2 years in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive placebo PO QD for 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 6 months, every 6 months for 3 years, and then annually thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients must have histological proof of a primary non-small cell lung cancer (bronchoalveolar carcinomas presenting as a discrete solitary radiological mass or nodule are eligible)
- •Patients must be classified post-operatively as stage IB, II or IIIA on the basis of pathologic criteria
- •At the time of resection a complete mediastinal lymph node resection or at least lymph node sampling should have been attempted; if a complete mediastinal lymph node resection or lymph node sampling was not undertaken, any mediastinal lymph node which measured 1.5 cm or more on the pre-surgical computed tomography (CT)/magnetic resonance imaging (MRI) scan or any area of increased uptake in the mediastinum on a pre-surgical positron emission tomography (PET) scan must have been biopsied; note: a pre-surgical PET scan is not mandatory
- •The nodal tissue must be labelled according to the recommendations of the American Thoracic Society; surgeons are encouraged to dissect or sample all accessible nodal levels; the desirable levels for biopsy are:
- •Right upper lobe: 4, 7, 10
- •Right middle lobe: 4, 7, 10
- •Right lower lobe: 4, 7, 9, 10
- •Left upper lobe: 5, 6, 7, 10
- •Left lower lobe: 7, 9, 10
- •Surgery may consist of lobectomy, sleeve resection, bilobectomy or pneumonectomy as determined by the attending surgeon based on the intraoperative findings; patients who have had only segmentectomies or wedge resections are not eligible for this study; all gross disease must have been removed at the end of surgery; all surgical margins of resection must be negative for tumor
Exclusion Criteria
- •Prior or concurrent malignancies; patients who have had a previous diagnosis of cancer, if they remain free of recurrence and metastases five years or more following the end of treatment and, in the opinion of the treating physician do not have a substantial risk of recurrence of the prior malignancy, are eligible for the study; patients who have been adequately treated for non-melanomatous skin cancer or carcinoma in situ of the cervix are eligible irrespective of when that treatment was given
- •A combination of small cell and non-small cell carcinomas or a pulmonary carcinoid tumor
- •More than one discrete area of apparent primary cancer (even if within the same lobe, T4, IIIB)
- •Clinically significant or untreated ophthalmologic (e.g. Sjogren's etc.) or gastrointestinal conditions (e.g. Crohn's disease, ulcerative colitis)
- •Any active pathological condition that would render the protocol treatment dangerous such as: uncontrolled congestive heart failure, angina, or arrhythmias, active uncontrolled infection, or others
- •A history of psychiatric or neurological disorder that would make the obtainment of informed consent problematic or that would limit compliance with study requirements
- •Patient, if female, is pregnant or breast-feeding
- •Neoadjuvant chemotherapy or immunotherapy for NSCLC; however, patients may have received pre-operative limited field, low dose (less than 1000 cGy) external beam radiation therapy or endobronchial brachytherapy or laser therapy for short term control of hemoptysis or lobar obstruction; full dose pre-operative radiotherapy of curative intent is a cause for exclusion; patients may have received post-operative adjuvant platinum-based chemotherapy however non-platinum-based chemotherapy is a cause for exclusion
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used on this trial; patients with ongoing use of phenytoin, carbamazepine, barbiturates, rifampicin, or St John's Wort are excluded
- •Incomplete healing from previous oncologic or other major surgery
Arms & Interventions
Arm I (gefitinib)
Patients receive gefitinib PO QD for 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: gefitinib
Arm I (gefitinib)
Patients receive gefitinib PO QD for 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Arm II (placebo)
Patients receive placebo PO QD for 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: placebo
Arm II (placebo)
Patients receive placebo PO QD for 2 years in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Overall Survival
Time Frame: From randomization to the time of death from any cause, assessed up to 5 years
The survival experience of patients in both treatment groups will be described by the Kaplan-Meier method. A stratified log-rank test will be used as the primary method to compare the overall survival between two arms adjusting for the stratification factors. An unadjusted analysis will also be performed. Five years survival rate will be reported.
Secondary Outcomes
- Disease Free Survival(From randomization to the time of documented recurrence of the primary cancer, assessed up to 5 years)
- Incidence of Toxicities Graded Using the NCI Common Terminology Criteria for Adverse Events Version 3.0(Up to 5 years)