AZD2171 in Treating Patients With Recurrent Small Cell Lung Cancer
Condition: Recurrent Non-small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Recurrence
Intervention: cediranib maleate; laboratory biomarker analysis; pharmacogenomic studies
Intervention description: Given PO; Correlative studies; Optional correlative studies
Intervention MeSH terms: Cediranib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well AZD2171 works in treating patients with recurrent
      small cell lung cancer. AZD2171 may stop the growth of tumor cells by blocking some of the
      enzymes needed for cell growth and by blocking blood flow to the tumor.
    

Eligibility criteria:

        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