Gefitinib and Everolimus in Treating Patients With Stage IIIB or Stage IV or Recurrent Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

- Determine the maximum tolerated dose of everolimus when administered with gefitinib in
patients with stage IIIB or IV or recurrent non-small cell lung cancer. (Phase I)

- Determine the efficacy of this regimen in these patients. (Phase II)

Secondary

- Assess the pharmacokinetics of everolimus, alone and in combination with gefitinib, in
these patients. (Phase I)

OUTLINE: This is an open-label, phase I, dose-escalation study of everolimus followed by a
phase II study.

- Phase I: Patients receive oral everolimus once on day 1. Beginning on day 8, patients
receive oral gefitinib once daily. Beginning on day 22, patients receive oral
everolimus once daily. Both drugs are then given concurrently for the rest of the
treatment. Treatment continues in the absence of disease progression or unacceptable
toxicity.

Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6
patients experiences dose-limiting toxicity.

- Phase II: Patients receive oral everolimus at the MTD determined in phase I and oral
gefitinib once daily. Treatment continues in the absence of disease progression or
unacceptable toxicity.

DISEASE CHARACTERISTICS:

- Histologically confirmed non-small cell lung cancer (NSCLC) meeting 1 of the
following stage criteria:

- Stage IIIB (unresectable, with malignant pleural or pericardial effusion)

- Stage IV disease

- Recurrent disease

- Measurable or evaluable indicator lesions

- Progressive disease after receiving ≥ 1 prior chemotherapy regimen that included
cisplatin or carboplatin and docetaxel

- No uncontrolled brain or leptomeningeal metastases

- Must not require concurrent glucocorticoids for control of metastases

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- Karnofsky 70-100% OR

- ECOG 0-2

Life expectancy

- Not specified

Hematopoietic

- WBC ≥ 3,000/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 9.0 g/dL

Hepatic

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST ≤ 2.5 times ULN

Renal

- Creatinine ≤ 1.5 times ULN OR

- Creatinine clearance ≥ 60 mL/min

Cardiovascular

- No congestive heart failure

- No New York Heart Association class III or IV heart disease

- No unstable angina

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No severe infection

- No severe malnutrition

- No other serious medical illness

- No other malignancy within the past 3 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No concurrent biologic therapy

- No concurrent immunotherapy

Chemotherapy

- See Disease Characteristics

- No prior conventional chemotherapy for metastatic or recurrent NSCLC (phase II only)

- At least 4 weeks since prior chemotherapy

- No other concurrent chemotherapy

Endocrine therapy

- See Disease Characteristics

- No concurrent oral steroids for management of skin toxicity

Radiotherapy

- At least 4 weeks since prior radiotherapy

- No concurrent radiotherapy

Surgery

- At least 4 weeks since prior major surgery

- No concurrent surgery for an identifiable lesion

Other

- Recovered from all prior therapy

- No prior gefitinib, erlotinib, or other epidermal growth factor tyrosine kinase
inhibitor

- No concurrent cytotoxic therapy (e.g., methotrexate for rheumatoid arthritis)

- No other concurrent oncolytic agents