Recurrent Non-small Cell Lung Cancer
Conditions
Brief 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.
Detailed 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.
Interventions
DRUGcediranib maleate
Given PO
OTHERlaboratory biomarker analysis
Correlative studies
OTHERpharmacogenomic studies
Optional correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to 4 weeks | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT, MRI or X-Ray: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A Patients receive oral AZD2171 45 mg once daily for 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cediranib maleate: Given PO | 12 |
| Arm B Patients receive oral AZD2171 30 mg once daily for 28 days. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
cediranib maleate: Given PO | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 5 |
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Arm B | Total | Arm A |
|---|---|---|---|
| Age, Continuous | 60 years | 61 years | 63 years |
| Region of Enrollment United States | 13 participants | 25 participants | 12 participants |
| Sex: Female, Male Female | 5 Participants | 12 Participants | 7 Participants |
| Sex: Female, Male Male | 8 Participants | 13 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 12 | 13 / 13 |
| serious Total, serious adverse events | 5 / 12 | 5 / 13 |
Outcome results
Primary
Objective Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT, MRI or X-Ray: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 4 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Objective Response Rate | 0 percentage of responding patients |
| Arm B | Objective Response Rate | 0 percentage of responding patients |