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 =\< 1.5 times upper limit of normal (ULN)
• •AST and ALT =\< 2.5 times ULN (\< 5 times ULN if liver metastases present)
• •Creatinine normal OR creatinine clearance \>= 60 mL/min
• •Urine protein =\< 1+ on 2 consecutive dipsticks taken \>= 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 \< 470 msec by ECG
• •No history of familial long QT syndrome
• •Fertile patients must use effective contraception
• •No resting blood pressure (BP) consistently \> 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
• •* Clarithromycin
• •* Disopyramide
• •* Dofetilide
• •* Domperidone
• •* Droperidol
• •* Erythromycin
• •* Halofantrine
• •* Haloperidol
• •* Ibutilide
• •* Mesoridazine
• •* Methadone
• •* Pentamidine
• •* Pimozide
• •* Procainamide
• •* Sotalol
• •* Sparfloxacin
• •* Thioridazine
• •Not pregnant or nursing
• •More than 30 days since prior investigational agents and recovered
• •No aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) for 2 days before, during, and for 2 days after pemetrexed disodium administration: Low-dose aspirin (≤ 325 mg/day) for vascular disorders allowed
• •No long-acting NSAIDs (e.g., naproxen, piroxicam, diflunisal, nabumetone, or celecoxib) for 5 days before, during, and for 2 days after pemetrexed disodium
• •No concurrent combination antiretroviral therapy for HIV-positive patients
• •No other concurrent anticancer agents or therapies
• •No other concurrent investigational agents
• •Life expectancy \> 12 weeks
• •No concurrent medications that can markedly affect renal function (e.g., vancomycin or amphotericin)
• •Negative pregnancy test
• •Relapsed disease