A Randomized Phase II Study of ALIMTA® (Pemetrexed) and GEMZAR® (Gemcitabine) Every 14 Days Versus Pemetrexed and Gemcitabine Every 21 Days in Advanced Non-Small Cell Lung Cancer

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

- Stage IIIB (with controlled pleural effusion) OR stage IV disease

- At least 1 measurable lesion whose longest diameter is ≥ 20 mm by conventional
techniques OR ≥ 10 mm by spiral CT scan

- No medically significant third-space fluid collection (e.g., ascites or pleural
effusions) that cannot be controlled by drainage or other procedures

- No documented brain metastases unless all of the following criteria are met:

- Successful local therapy has been completed

- At least 2 weeks since prior corticosteroids

- Brain imaging required for symptomatic patients only (to rule out brain
metastases)

- Concurrent enrollment in clinical trial MCCRC-RC0527 required

PATIENT CHARACTERISTICS:

- Life expectancy ≥ 12 weeks

- ECOG performance status 0-1

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9.0 g/dL

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

- Alkaline phosphatase ≤ 3 times ULN

- AST and ALT ≤ 3 times ULN (5 times ULN for liver involvement)

- Creatinine clearance ≥ 45 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- Able to take folic acid, cyanocobalamin (vitamin B12) supplementation, or
dexamethasone and corticosteroids

- Able to interrupt intake of aspirin and nonsteroidal anti-inflammatory agents for a
total of 5 days

- No severe and/or uncontrolled medical conditions, including any of the following:

- Hypertension, labile hypertension, or history of poor compliance with
antihypertensive medication

- Angina pectoris

- Congestive heart failure within the past 3 months, unless ejection fraction >
40%

- Myocardial infarction within the past 6 months

- Cardiac arrhythmia

- Diabetes

- Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the
lung

- New York Heart Association class III or IV heart disease

- Clinically significant infection

- No other serious medical condition or illness that would preclude study participation

- No peripheral neuropathy ≥ grade 2

- No other malignancy within the past 5 years except nonmelanomatous skin cancer,
carcinoma in situ of the cervix, or low-grade (Gleason score ≤ 6) localized prostate
cancer

- No significant weight loss (≥ 10%) within the past 6 weeks

- No investigator site personnel directly affiliated with the study, or immediate
family (i.e., spouse, parent, child, or sibling, whether biological or legally
adopted)

- No employees of Eli Lilly (i.e., employees, temporary contract workers, or designees
responsible for conducting the study)

- Immediate family of Eli Lilly employees may participate in Eli Lilly-sponsored
clinical trials, but are not permitted to participate at an Eli Lilly facility

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- At least 2 weeks since prior corticosteroids

- At least 4 weeks since prior radiation therapy involving > 25% of the bone marrow and
recovered

- At least 30 days since prior investigational therapy

- No prior radiation therapy to the whole pelvis

- No prior systemic chemotherapy for advanced non-small cell lung cancer

- No prior pemetrexed disodium and/or gemcitabine hydrochloride

- No prior or concurrent sorafenib tosylate and/or temsirolimus

- No concurrent Hypericum perforatum (St. John's wort)

- No other concurrent antitumor therapy

- No concurrent agents that stimulate thrombopoiesis

- Concurrent palliative radiation therapy allowed

- Concurrent corticosteroids allowed for adrenal insufficiency or severe nausea and
vomiting