Gefitinib in Treating Patients With Non-Small Cell Lung Cancer That Has Been Surgically Removed - Full Text View

Sponsor:	NCIC Clinical Trials Group
Collaborators:	National Cancer Institute (NCI) Eastern Cooperative Oncology Group Southwest Oncology Group
Information provided by (Responsible Party):	NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00049543

Purpose

RATIONALE: Biological therapies such as gefitinib may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether gefitinib is effective in delaying the recurrence of non-small cell lung cancer.

PURPOSE: This randomized phase III trial is studying gefitinib to see how well it works compared to placebo in treating patients who have undergone surgery for stage IB, stage II, or stage IIIA non-small cell lung cancer.

Condition	Intervention	Phase
Lung Cancer	Drug: IRESSA (ZD1839) Other: Placebo comparator	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: ZD1839

U.S. FDA Resources

Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:

Overall survival [ Time Frame: approximately 6 years ] [ Designated as safety issue: No ]
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)

Secondary Outcome Measures:

Disease free survival [ Time Frame: approxmately 3 years ] [ Designated as safety issue: No ]
Prognostic significance of EGFR expression [ Time Frame: approxmately 3 years ] [ Designated as safety issue: No ]
Toxicity of ZD1839 [ Time Frame: every 6 months ] [ Designated as safety issue: Yes ]
Adverse events will be monitored on an ongoing basis by the central office and presented every 6 months in an unblinded fashion to the Data Safety Monitoring Committee of the NCIC CTG.

Enrollment:	503
Study Start Date:	September 2002
Study Completion Date:	January 2012
Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: IRESSA (ZD1839)	Drug: IRESSA (ZD1839) 250mg daily oral dose for 2 years
Placebo Comparator: Placebo	Other: Placebo comparator daily oral dose of 250mg tablet for 2yrs (matching placebo comparator)

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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])

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049543

Locations

Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
BCCA - Vancouver Island Cancer Centre
Victoria, British Columbia, Canada, V8R 6V5
Canada, New Brunswick
Atlantic Health Sciences Corporation
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Newfoundland and Labrador
Dr. H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, Canada, AIB 3V6
Canada, Ontario
Cancer Centre of Southeastern Ontario at Kingston
Kingston, Ontario, Canada, K7L 5P9
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Lakeridge Health Oshawa
Oshawa, Ontario, Canada, L1G 2B9
Ottawa Health Research Institute - General Division
Ottawa, Ontario, Canada, K1H 8L6
Algoma District Cancer Program
Sault Ste. Marie, Ontario, Canada, P6B 0A8
Niagara Health System
St. Catharines, Ontario, Canada, L2R 7C6
Regional Cancer Program of the Hopital Regional
Sudbury, Ontario, Canada, P3E 5J1
Thunder Bay Regional Health Science Centre
Thunder Bay, Ontario, Canada, P7B 6V4
Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
St. Joseph's Health Centre
Toronto, Ontario, Canada, M6R 1B5
Trillium Health Centre - West Toronto
Toronto, Ontario, Canada, M9C 1A5
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Windsor Regional Cancer Centre
Windsor, Ontario, Canada, N8W 2X3
Canada, Prince Edward Island
PEI Cancer Treatment Centre,Queen Elizabeth Hospital
Charlottetown, Prince Edward Island, Canada, C1A 8T5
Canada, Quebec
Hopital Charles LeMoyne
Greenfield Park, Quebec, Canada, J4V 2H1
L'Hotel-Dieu de Levis
Levis, Quebec, Canada, G6V 3Z1
Hopital du Sacre-Coeur de Montreal
Montreal, Quebec, Canada, H4J 1C5
CHUM - Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada, S7N 4H4
Canada
University Institute of Cardiology and
Quebec, Canada, G1V 4G5

Sponsors and Collaborators

NCIC Clinical Trials Group

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Southwest Oncology Group

Investigators

Study Chair:	Glenwood D. Goss, MD, BCh, FCP, FRCPC	Ottawa Regional Cancer Centre
Study Chair:	Gregory A. Masters, MD	Robert H. Lurie Cancer Center
Study Chair:	Peter F. Roberts, MD	University of California, Davis

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:	NCT00049543 History of Changes
Obsolete Identifiers:	NCT00953069
Other Study ID Numbers:	BR19, CAN-NCIC-BR19, ECOG-CAN-NCIC-BR19, SWOG-CAN-NCIC-BR19, CDR0000258118
Study First Received:	November 12, 2002
Last Updated:	January 9, 2012
Health Authority:	United States: Food and Drug Administration; Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:

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

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
Gefitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012