Brief Title
Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
Official Title
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
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.
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Overall Survival
Secondary Outcome
Disease Free Survival
Condition
Adenocarcinoma of the Lung
Intervention
gefitinib
Study Arms / Comparison Groups
Arm I (gefitinib)
Description: Patients receive gefitinib PO QD for 2 years in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
503
Start Date
September 2002
Completion Date
April 2011
Primary Completion Date
April 2011
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
- No more than 16 weeks may have elapsed between surgery and randomization; for patients
who received post-operative adjuvant platinum-based chemotherapy, no more than 26
weeks may have elapsed between surgery and randomization
- Patient must consent to provision of and investigator(s) must agree to submit a
representative formalin fixed paraffin block of tumor tissue at the request of the
Central Tumor Bank in order that the specific EGFR correlative marker assays may be
conducted
- The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
of 0, 1 or 2
- Leukocytes >= 3.0 x 10^9/L or >= 3000/ul
- Absolute granulocyte count >= 1.5 x 10^9/L or >= 1,500/ul
- Platelets >= 100 x 10^9/L or >= 100,000/ul
- Total bilirubin within normal institutional limits
- Alkaline phosphatase =< 2.5 x institutional upper limit of normal; if alkaline
phosphatase is greater than the institutional upper limit of normal (UNL) but less
than the maximum allowed, an abdominal (including liver) ultrasound, CT or MRI scan
and a radionuclide bone scan must be performed prior to randomization to rule out
metastatic disease; if the values are greater than the maximum allowed, patients will
not be considered eligible regardless of findings on any supplementary imaging
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
and/or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 x institutional upper limit of normal; if AST (SGOT) or ALT (SGPT) are greater
than the institutional upper limit of normal (UNL) but less than the maximum allowed,
an abdominal (including liver) ultrasound, CT or MRI scan must be performed prior to
randomization to rule out metastatic disease; if the values are greater than the
maximum allowed, patients will not be considered eligible regardless of findings on
any supplementary imaging
- Patient must have a chest x-ray done within 14 days prior to randomization; patient
must have a CT or MRI scan of the chest done within 90 days prior to surgical
resection if at least one of the following was undertaken:
- A complete mediastinal lymph node resection; or
- Biopsy of all desired levels of lymph nodes - as specified above; or
- A pre-surgical PET scan within 60 days prior to surgical resection If none of the
above was undertaken then the CT or MRI scan of the chest must have been
performed within 60 days prior to surgical resection Note: a pre-surgical PET
scan is not mandatory
- Patient must have an electrocardiogram (EKG) done within 14 days prior to
randomization
- Women of childbearing age and men must agree to use adequate contraception (hormonal
or barrier method of birth control) prior to study entry and while taking study
medication and for a period of three months after final dose; should a woman become
pregnant or suspect she is pregnant while she or her male partner are participating in
this study, she should inform her treating physician immediately
- Patients may receive post-operative radiation therapy; patients must have completed
radiation at least 3 weeks prior to randomization and have recovered from all
radiation-induced toxicity; patients who have received radiation therapy should also
be randomized within 16 weeks of surgery
- Patient consent must be obtained according to local institutional and/or University
Human Experimentation Committee requirements; it will be the responsibility of the
local participating investigators to obtain the necessary local clearance, and to
indicate in writing to either the National Cancer Institute of Canada (NCIC) Clinical
Trials Group (CTG) study coordinator (for NCIC CTG centers) or the Cancer Trials
Support Unit (CTSU) (for all other investigators), that such clearance has been
obtained, before the trial can commence in that center; a standard consent form for
the trial will not be provided, but a sample form is given; this sample consent form
has been approved by the National Cancer Institute (NCI) Central Institutional Review
Board (IRB) and must be used unaltered by those CTSI centers which operate under CIRB
authority; for NCIC CTG centers, a copy of the initial full board Research Ethics
Board (REB) approval and approved consent form must be sent to the NCIC CTG central
office; please note that the consent form for this study must contain a statement
which gives permission for the government agencies, NCI, NCIC CTG and monitoring
agencies to review patient records
- NCIC-CTG Centers: the patient must have the ability to understand and the
willingness to sign a written informed consent document; the patient must sign
the consent form prior to randomization
- CTSU Centers: the patient, or in the case of a mentally incompetent patient his
or her legally authorized and qualified representative, must have the ability to
understand and the willingness to sign a written informed consent document; the
consent form must be signed prior to randomization
- Patients must be accessible for treatment and follow-up; investigators must assure
themselves that patients registered on this trial will be available for complete
documentation of the treatment administered, toxicity and follow-up
- Initiation of protocol treatment must begin within 10 working days of patient
randomization
- Patients may have received post-operative adjuvant platinum-based chemotherapy;
patients must have completed chemotherapy at least 3 weeks prior to randomization and
have recovered from all chemotherapy-induced toxicity; patients who have received
adjuvant chemotherapy should also be randomized within 26 weeks of surgery
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Glennwood Goss, ,
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT00049543
Organization ID
NCI-2014-00650
Secondary IDs
NCI-2014-00650
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Glennwood Goss, Principal Investigator, Canadian Cancer Trials Group
Verification Date
March 2014