Gefitinib in Treating Patients With Previously Untreated Stage IIIB or Stage IV Non-Small Cell Lung Cancer

A Phase II, Open Label Study of Gefitinib (IRESSA) in Treatment-Naïve Subjects With Stage IIIB or IV Non-Small Cell Lung Cancer and Somatic Activating Mutations in the Epidermal Growth Factor Receptor

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well gefitinib works in treating patients with previously untreated stage IIIB or stage IV non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: gefitinib

Detailed Description

OBJECTIVES:

Primary

• Determine the objective tumor response rate in patients with previously untreated stage IIIB or IV non-small cell lung cancer with somatic activating mutations in the TK region of the epidermal growth factor receptor (EGFR) gene treated with gefitinib.

Secondary

• Determine response duration, progression-free survival, and overall survival of patients treated with this drug.
• Determine the safety of this drug in these patients.
• Compare the ability of various somatic activating mutations in the TK region of the EGFR gene to predict response in patients treated with this drug.
• Compare the ability of various somatic activating mutations in the TK region of the EGFR gene to predict toxicity of this drug in these patients.
• Define a molecular profile in patients who initially respond to treatment with this drug but subsequently progress on therapy.
• Determine the significance of germline polymorphisms of the EGFR gene, somatic amplification of the EGFR gene, and other molecular factors for their association with clinical outcome parameters in these patients.

OUTLINE: This is an open-label study.

Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Pathologically confirmed non-small cell lung cancer (NSCLC)

  • No squamous cell histology
• Stage IIIB (with pleural effusion) or stage IV disease

• Must meet ≥ 1 of the following criteria:

  • Female
  • Adenocarcinoma tumor histology
  • No history of smoking, defined as smoking < 100 cigarettes (5 standard packs of cigarettes) in a lifetime, < 20 oz of pipe tobacco in a lifetime, OR < 100 cigars in a lifetime
  • Asian/Pacific Rim ethnicity, defined as Japanese, Chinese, Korean, or other Asian/Pacific Rim ethnicity
• Must have activating mutations in the TK region of the epidermal growth factor receptor (EGFR) gene
• Measurable disease

• No symptomatic or newly diagnosed CNS metastases that have not been definitively treated with radiotherapy and/or surgery

  • History of CNS metastases or cord compression allowed if definitively treated and clinically stable

PATIENT CHARACTERISTICS:

• See Disease Characteristics
• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Absolute neutrophil count ≥ 2,000/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.25 times upper limit of normal (ULN)
• ALT and AST ≤ 2.5 times ULN (5 times ULN if liver has tumor involvement)
• Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No known severe hypersensitivity to gefitinib or any other component of gefitinib tablets

• No evidence of clinically active interstitial lung disease

  • Patients with chronic, stable radiographic changes who are asymptomatic are eligible
• No other concurrent malignancy or malignancy diagnosed within the past 5 years except for basal cell carcinoma of the skin or cervical cancer in situ
• No concurrent severe or uncontrolled systemic disorder
• No evidence of any other significant clinical disorder or laboratory finding that, in the opinion of the investigator, would preclude study participation
• Able to tolerate protocol treatment, in the opinion of the investigator

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior systemic chemotherapy, biological therapy, immunotherapy, or hormonal therapy for NSCLC, including adjuvant and neoadjuvant treatment

• No prior radiotherapy to the target lesion

  • Prior radiotherapy to bony disease or CNS disease allowed
• At least 2 weeks since prior radiotherapy and recovered
• More than 30 days since prior non-FDA approved or investigational agents
• No prior EGFR antagonists
• At least 2 weeks since prior and no concurrent phenytoin, carbamazepine, rifampin, barbiturates, or Hypericum perforatum (St. John's wort)
• No concurrent chemotherapy, immunotherapy, hormonal therapy, nonpalliative radiotherapy, surgery for cancer, or other experimental medications
• No other concurrent specific antitumor therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Objective tumor response rate

Secondary Outcome Measures

Outcome Measure
Safety
Response duration, progression-free survival, and overall survival
Ability of various somatic activating mutations in the TK region of the epidermal growth factor receptor (EGFR) gene to predict response and toxicity
Molecular profile
Significance of germline polymorphisms of the EGFR gene, somatic amplification of the EGFR gene, and other molecular factors for their association with clinical outcome parameters

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Lecia V Sequist, MD, MPH, Massachusetts General Hospital

Publications and helpful links

Helpful Links

• Clinical trial summary from the National Cancer Institute's PDQ® database

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: December 11, 2006
• First Submitted That Met QC Criteria: December 11, 2006
• First Posted (Estimate): December 13, 2006

Study Record Updates

• Last Update Posted (Estimate): May 14, 2013
• Last Update Submitted That Met QC Criteria: May 12, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: stage IIIB non-small cell lung cancer; stage IV non-small cell lung cancer; large cell lung cancer; adenocarcinoma of the lung; bronchoalveolar cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Gefitinib
• Other Study ID Numbers: 04-291; IRUSIRES0483 (Other Identifier: AstraZeneca)