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
18 Years
N/A
Both
Lung Cancer
Trial Information
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
OBJECTIVES:
Primary
- Compare the overall survival of patients with completely resected primary stage IB, II,
or IIIA non-small cell lung cancer treated with gefitinib vs placebo.
Secondary
- Compare the disease-free survival of patients treated with these regimens.
- Determine the prognostic significance of epidermal growth factor receptor expression,
phosphorylation, and mutations in the primary tumor in predicting relative impact of
gefitinib on survival of these patients.
- Establish a comprehensive tumor bank linked to a clinical database for further study of
molecular markers in patients treated with these regimens.
- Determine the toxicity of gefitinib in these patients.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to disease stage (IB vs II vs IIIA), histological subtype (squamous
cell vs others), postoperative radiotherapy (yes vs no), prior adjuvant platinum-based
chemotherapy (yes vs no), and gender. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral gefitinib daily, unless otherwise directed by the
investigator.
- Arm II: Patients receive oral placebo daily, unless otherwise directed by the
investigator.
Treatment in both arms continues for up to 2 years in the absence of disease progression or
unacceptable toxicity.
Patients are followed at 1 month, 3 months, and every 3 months for 30 months after
randomization, then every 6 months for 3 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 1,242 patients (621 per treatment arm) will be accrued for
this study within 3.5 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed primary non-small cell lung cancer (NSCLC)
- Bronchoalveolar carcinoma presenting as discrete solitary radiological mass or
nodule allowed
- Stage IB, II, or IIIA disease
- Completely resected by lobectomy, sleeve resection, bilobectomy, or
pneumonectomy within the past 16 weeks (26 weeks for patients who received
adjuvant platinum-based chemotherapy)
- Mediastinal lymph node resection or lymph node sampling attempted with no
evidence of metastatic involvement
- Patients without a complete mediastinal lymph node resection or lymph node
sampling must have undergone biopsy of any mediastinal lymph node measuring
1.5 cm or more on pre-surgical CT/MRI scan or any area of increased uptake
in the mediastinum on pre-surgical PET scan
- No combination of small cell and non-small cell carcinoma or pulmonary carcinoid
tumor
- No more than 1 discrete area of apparent primary cancer (even within the same lobe)
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- WBC at least 3,000/mm^3
- Absolute granulocyte count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
Hepatic
- Bilirubin normal
- AST/ALT no greater than 2.5 times upper limit of normal (ULN)
- Alkaline phosphatase no greater than 2.5 times ULN
Renal
- Creatinine no greater than 1.5 times ULN
Cardiovascular
- No uncontrolled congestive heart failure
- No angina
- No arrhythmias
Other
- No active uncontrolled infection
- No clinically significant or untreated ophthalmologic conditions (e.g., Sjögren's
syndrome)
- No clinically significant or untreated gastrointestinal conditions (e.g., Crohn's
disease or ulcerative colitis)
- No other malignancy within the past 5 years except adequately treated nonmelanoma
skin cancer or carcinoma in situ of the cervix
- No other concurrent malignancy
- No prior allergic reaction to compounds of similar chemical or biological composition
to gefitinib
- No history of psychiatric or neurologic disorder that would preclude study compliance
- No active pathological condition that would preclude study participation
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study
participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior neoadjuvant immunotherapy for NSCLC
Chemotherapy
- See Disease Characteristics
- Prior adjuvant platinum-based chemotherapy allowed
- At least 3 weeks since prior adjuvant platinum-based chemotherapy for NSCLC and
recovered
- No prior non-platinum-based chemotherapy
- No prior neoadjuvant chemotherapy for NSCLC
Endocrine therapy
- Not specified
Radiotherapy
- Prior preoperative limited-field, low-dose external beam radiotherapy (less than
1,000 cGy) or endobronchial brachytherapy allowed
- At least 3 weeks since prior radiotherapy and recovered
- No prior full-dose preoperative radiotherapy with curative intent
Surgery
- See Disease Characteristics
- Recovered from prior oncologic or other major surgery
Other
- Prior laser therapy for short-term control of hemoptysis or lobar obstruction allowed
- No other concurrent anticancer therapy
- No concurrent drugs that induce CYP3A4 enzymes (e.g., phenytoin, carbamazepine,
barbiturates, rifampin, or Hypericum perforatum [St. John's wort])
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Outcome Measure:
Overall survival
Outcome Description:
The 3-year survival for the 60% of patients with stage IB and II together is about 63% for those who did not receive post-operative chemotherapy, and is 67% for those who had received post-operative chemotherapy. Assuming 75% of patients may receive post-operative chemotherapy, the corresponding median survival for this subgroup of patients is about 64 months (5.3 years)
Outcome Time Frame:
approximately 6 years
Safety Issue:
No
Principal Investigator
Glenwood D. Goss, MD, BCh, FCP, FRCPC
Investigator Role:
Study Chair
Investigator Affiliation:
Ottawa Regional Cancer Centre
Authority:
United States: Food and Drug Administration
Study ID:
BR19
NCT ID:
NCT00049543
Start Date:
September 2002
Completion Date:
January 2012
Related Keywords:
- Lung Cancer
- adenocarcinoma of the lung
- adenosquamous cell lung cancer
- bronchoalveolar cell lung cancer
- large cell lung cancer
- squamous cell lung cancer
- stage I non-small cell lung cancer
- stage II non-small cell lung cancer
- stage IIIA non-small cell lung cancer
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
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