RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of non-small cell lung cancer cells. Hormone therapy using fulvestrant may fight non-small cell lung cancer by lowering the amount of estrogen the body makes. Giving gefitinib together with fulvestrant may kill more tumor cells. It is not yet known whether giving gefitinib together with fulvestrant is more effective than gefitinib alone in treating non-small cell lung cancer.

PURPOSE: This randomized phase II trial is studying gefitinib and fulvestrant to see how well they work when given together compared to gefitinib alone in treating patients with stage IIIB or stage IV non-small cell lung cancer.

Condition	Treatment or Intervention	Phase
stage IIIB non-small cell lung cancer stage IV non-small cell lung cancer recurrent non-small cell lung cancer	Drug: fulvestrant  Drug: gefitinib  Procedure: antiestrogen therapy  Procedure: endocrine therapy  Procedure: enzyme inhibitor therapy  Procedure: hormone therapy  Procedure: protein tyrosine kinase inhibitor therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Compare objective tumor response in patients with epidermal growth factor (EGF) receptor- and estrogen receptor (ER)-positive stage IIIB or IV non-small cell lung cancer treated with gefitinib with vs without fulvestrant.

Secondary

• Correlate response rate with ER and EGF receptor expression in patients treated with these regimens.
• Correlate measurement of ER-α, ER-β, EGF/HER-1 receptor and HER-2/neu receptor with clinical response in patients treated with these regimens.
• Correlate gefitinib resistance with ER and HER receptor expression in patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to performance status, gender, and participating center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral gefitinib once daily on days 1-28. Courses repeat every 28 days.
• Arm II: Patients receive gefitinib as in arm I and fulvestrant intramuscularly on days 1, 15, and 29, and then every 28 days thereafter. In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed for 30 days and then every 2 months until disease progression.

PROJECTED ACCRUAL: A total of 102 patients (34 in arm I and 68 in arm II) will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer
• Stage IIIB or IV disease
• Measurable disease
• Epidermal growth factor receptor-positive AND estrogen receptor-positive tumor
• Meets 1 of the following criteria:
• Progressive disease after ≥ 2 prior standard chemotherapy regimens
• Refused chemotherapy
• Unable to receive standard chemotherapy
• Tumor tissue block must be available
• No active CNS metastasis

PATIENT CHARACTERISTICS: Age

• Over 18

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 mg/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• PT and/or PTT ≤ 1.5 times ULN

Renal

• Creatinine ≤ 2 mg/dL

Cardiovascular

• No New York Heart Association class III or IV cardiac disease
• No myocardial infarction within the past 12 months
• No symptomatic ventricular arrhythmia
• No symptomatic conduction abnormality

Pulmonary

• No evidence of clinically active interstitial lung disease
• Patients with asymptomatic chronic stable radiographic changes are eligible

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No hypersensitivity to gefitinib or fulvestrant or to any of their excipients
• No other disease or medical condition that would preclude study treatment or compliance
• No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• More than 4 weeks since prior chemotherapy

Endocrine therapy

• No prior anticancer antiestrogen therapy
• Concurrent stable-dose steroids allowed

Radiotherapy

• More than 4 weeks since prior radiotherapy
• No concurrent radiotherapy to the lungs

Surgery

• At least 7 days since prior surgery and recovered

Other

• No prior anticancer epidermal growth factor receptor inhibitors
• More than 4 weeks since prior non-cytotoxic investigational agents
• No concurrent CYP3A4 inducers, including any of the following:
• Phenytoin
• Carbamazepine
• Rifampin
• Barbiturates
• Hypericum perforatum (St. John's wort)

California
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-5907,  United States
Pennsylvania
      Hillman Cancer Center at University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15232,  United States

Study chairs or principal investigators

Robert Alan Figlin, MD, FACP,  Principal Investigator,  Jonsson Comprehensive Cancer Center   
Richard J. Pietras, MD, PhD,  Principal Investigator,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000407580; UCLA-0407058-01; NCT00100854
Record last reviewed:  February 2005
Last Updated:  February 24, 2005
Record first received:  January 6, 2005
ClinicalTrials.gov Identifier:  NCT00100854
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08