AZD2171 and Pemetrexed Disodium in Treating Patients With Relapsed Non-Small Cell Lung Cancer

Inclusion Criteria

• Histologically or cytologically confirmed non-small cell lung cancer
• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan
• Lesions in a previously irradiated area are considered measurable provided there has been an increase of >= 10 mm since completion of radiotherapy
• Received 1-2 prior regimens, including 1 doublet chemotherapy regimen, AND meets 1 of the following criteria:
• No prior bevacizumab (cohort A)
• Patients with squamous cell carcinoma, treated and controlled brain metastases, or history of hemoptysis allowed
• Received 1-2 prior regimens*, including 1 doublet chemotherapy regimen, AND meets 1 of the following criteria:
• Previously treated with bevacizumab (cohort B)
• No discontinuation of bevacizumab for uncontrollable hypertension and/or life-threatening bleeding
• Must have disease progression after prior bevacizumab (NOTE: *Prior adjuvant therapy is considered 1 regimen if disease progression occurred within 1 year of completion of therapy; if a regimen was discontinued within 2 courses for allergic reaction or unacceptable drug-specific toxicity, that regimen dose not count)
• No large pleural effusion or ascites unless drained
• No active brain metastases by brain MRI or CT scan within the past 4 weeks
• Patients with treated, controlled brain metastasis allowed provided they are neurologically stable without seizures within the past 3 weeks
• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• WBC >= 3,000/mm^3
• Bilirubin = = 60 mL/min
• Urine protein = = 1 week apart
• No significant hemorrhage (i.e., > 30 mL in 1 episode) within the past 3 months
• No significant hemoptysis (i.e., > 5 mL fresh blood in 1 episode) within the past 4 weeks
• No active gastrointestinal disease that may affect the ability of the patient to absorb AZD2171
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171 or pemetrexed disodium
• No other malignancies within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ
• No uncontrolled intercurrent illness including, but not limited to, any of the following:
• Ongoing or active infection
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness or social situation that would preclude study compliance
• No New York Heart Association class III or IV heart disease
• Mean QTc 140/90 mm Hg; Patients whose BP is controlled after starting, adjusting, or increasing medication allowed
• LVEF normal by MUGA or echocardiogram for patients at increased risk for left ventricular dysfunction, as evidenced by any of the following:
• Prior treatment with anthracyclines
• New York Heart Association class III or IV heart disease or controlled class II disease
• Prior central thoracic radiotherapy, including radiotherapy to the heart
• Myocardial infarction within the past 12 months
• At least 4 weeks since prior definitive chest radiotherapy (> 60 Gy) and recovered
• At least 3 months since prior craniotomy for resection of brain metastasis
• At least 3 weeks since prior radiotherapy for brain metastases
• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• At least 2 weeks since prior palliative radiotherapy
• At least 2 weeks since prior surgery (excluding the placement of vascular access or drainage of pleural effusion or ascites) and recovered
• No inability or unwillingness to take folic acid, cyanocobalamin (vitamin B12), or dexamethasone
• No prior pemetrexed disodium
• At least 5 half-lives since prior and no concurrent drugs or biologics with proarrythmic potential including:
• Amiodarone hydrochloride
• Arsenic trioxide
• Bepridil
• Chloroquine
• Chlorpromazine
• Cisapride
• Clarithrom