Phase II Study of AZD2171 in Patients With Recurrent Small Cell Lung Cancer

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed small cell lung cancer

- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded) as >=
20 mm with conventional techniques or as >= 10 mm with spiral CT scan

- Patients must have received prior platinum-based chemotherapy; no more than 1 prior
chemotherapy regimen is allowed

- Life expectancy of greater than 12 weeks

- Karnofsky performance status >= 50%

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Platelets >= 100,000/mcL

- Hemoglobin >= 8 g/dL

- Total bilirubin within normal institutional limits

- AST(SGOT)/ALT(SGPT) =< 2.5 × institutional upper limit of normal

- Creatinine within normal institutional limits OR creatinine clearance > >= 60
mL/min/1.73 m2 for patients with creatinine levels above institutional normal

- At present, the potential of AZD2171 for clinically significant drug interactions
involving the CYP isozymes is unknown; the only documented interaction is with CYP IA
agents/drugs; the other reported interactions were not seen in the dose ranges
studied and appears to occur at levels far beyond what can be and will be delivered
clinically; patients receiving CYP interactive concomitant medications should not be
excluded from study, but those agents/drugs should be documented along with any
associated AEs that occur; efforts should be made to switch patients with gliomas or
brain metastases who are taking enzyme-inducing anticonvulsant agents to other
medications

- AZD2171 has been shown to terminate fetal development in the rat, as expected for a
process dependent on VEGF signaling; for this reason, women of child-bearing
potential must have a negative pregnancy test prior to study entry; women of
child-bearing potential and men must agree to use adequate contraception (hormonal or
barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation; should a woman become pregnant or suspect she is
pregnant while participating in this study, she should inform her treating physician
immediately

- Ability to take oral medications on a regular basis

- Ability to understand and the willingness to sign a written informed consent document

- The following groups of patients will be considered to be at high risk for
compromised left ventricular ejection fraction (LVEF): prior treatment with
anthracyclines, prior treatment with trastuzumab, NYHA classification of, class II
heart failure controlled with appropriate therapy, prior central thoracic
radiotherapy including RT to the heart and history of myocardial infarction within 12
months; these patients are eligible for the study, but will require close monitoring

Exclusion Criteria:

- Patients who have had chemotherapy, radiotherapy, or major surgery within 4 weeks (6
weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have
not recovered from adverse events due to agents administered more than 4 weeks
earlier

- Patients may not be receiving any other investigational agents nor have participated
in an investigational trial within the past 30 days

- Patients may not be receiving any medication that may markedly affect renal function
(e.g., vancomycin, amphotericin, pentamidine)

- Patients with known brain metastases should be excluded from this clinical trial
because of their poor prognosis and because they often develop progressive neurologic
dysfunction that would confound the evaluation of neurologic and other adverse events

- Mean QTc > 500 msec (with Bazett's correction) in screening electrocardiogram or
history of familial long QT syndrome

- Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week
apart

- Uncontrolled intercurrent illness including, but not limited to hypertension, ongoing
or active infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements

- Pregnant women are excluded from this study because AZD2171 is a VEGF inhibitor with
known abortifacient effects; because there is an unknown but potential risk for
adverse events in nursing infants secondary to treatment of the mother with AZD2171,
breastfeeding should be discontinued if the mother is treated with AZD2171

- HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with AZD2171

- Patients with Class III or IV heart failure (NYHA) and those requiring concurrent use
of drugs with proarrhythmic potential