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

This phase II trial is studying how well giving AZD2171 together with pemetrexed disodium works in treating patients with relapsed non-small cell lung cancer. AZD2171 and pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. AZD2171 may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving AZD2171 together with pemetrexed disodium may kill more tumor cells.

PRIMARY OBJECTIVES:

I. Evaluate the response rate in patients with relapsed non-small cell lung cancer treated with AZD2171 and pemetrexed disodium.

SECONDARY OBJECTIVES:

I. Assess the progression-free and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study. Patients are stratified according to prior bevacizumab treatment (yes vs no).

Patients receive oral AZD2171 once daily on days 1-28 in course 1 and on days 1-21 in course 2 and all subsequent courses. Patients also receive pemetrexed disodium IV over 10 minutes on day 8 in course 1 and on day 1 in course 2 and all subsequent courses. Treatment repeats every 3 weeks\* in the absence of disease progression or unacceptable toxicity.

\[Note: \* The first course is 4 weeks in duration; all subsequent courses are 3 weeks in duration.\]

After completion of study treatment, patients are followed at 4 weeks and then periodically thereafter.

Eligibility Criteria:
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