Pemetrexed Disodium and Gemcitabine in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

• Compare response rates in patients with stage IIIB or IV non-small cell lung cancer treated with two different treatment schedules of pemetrexed disodium and gemcitabine hydrochloride.

Secondary

• Compare time-to-event efficacy variables in patients treated with these regimens.
• Compare progression-free and overall survival of patients treated with these regimens.
• Determine the overall toxicity of these regimens in these patients.

OUTLINE: This is a multicenter, open-label, randomized study. Patients are stratified according to disease stage (IIIB vs IV) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
• Arm II: Patients receive pemetrexed disodium IV over 10 minutes and gemcitabine hydrochloride IV over 30 minutes on day 1. Treatment repeats every 14 days for up to 9 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for up to 2 years.

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

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