AZD2171 in Treating Patients With Recurrent Small Cell Lung Cancer

National Cancer Institute (NCI)

Status and phase

Completed

Phase 2

Conditions

Recurrent Non-small Cell Lung Cancer

Treatments

Other: pharmacogenomic studies

Other: laboratory biomarker analysis

Drug: cediranib maleate

Study type

Interventional

Funder types

NIH

Identifiers

NCT00245063

PHII-64

N01CM62209 (U.S. NIH Grant/Contract)

N01CM62201 (U.S. NIH Grant/Contract)

NCI-2012-02837

Details and patient eligibility

About

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.

Full description

PRIMARY OBJECTIVES:

I. To determine the objective response rate of AZD 2171 in patients with recurrent small cell lung cancer (SCLC).

SECONDARY OBJECTIVES:

I. To determine the overall survival and time to progression. II. To assess the toxicities associated with the administration of AZD 2171 for patients with recurrent SCLC.

III. To perform molecular correlative studies on archival tumor and peripheral blood.

OUTLINE: This is a multicenter study.

Patients receive oral AZD2171 once daily for 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks.

Enrollment

25 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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