At this point in the treatment of extensive stage SCLC, we have reached a plateau in survival with conventional chemotherapy and newer regimens are greatly needed. It has been noted that patients with increased VEGF levels have a poorer prognosis. Anti-angiogenic agents hold significant promise in the treatment of patients with extensive stage SCLC. ZD6474, a new inhibitor of the VEGFR-2, has shown favorable action in NSCLC.
OUTLINE: This is a multi-center study. Arm A: Cisplatin 60mg/m2 Day 1 + Etoposide 120mg/m2 Day 1,2,3 + Placebo oral daily given continuously for the duration of the study Arm B: Cisplatin 60mg/m2 Day 1 + Etoposide 120mg/m2 Day 1,2,3 + ZD6474 100mg oral daily given continuously for the duration of the study For both arms, PE and toxicity evaluation prior to each cycle and disease assessment by imaging every 2 cycles. Patients with non-PD and acceptable toxicity will continue protocol therapy; patients with progressive disease or excessive toxicity will be taken off treatment. Cycles will be repeated every 21 days up to a total of 4 cycles. ECOG Performance Status of 0 or 1 Life Expectancy: Not specified Hematopoietic: * Platelets \> 100K/mm3 * Absolute neutrophil count (ANC) \> 1.5K/mm3 Hepatic: * Bilirubin \< 1.5 x ULN * Aspartate aminotransferase (AST) \< 2.5 x ULN or \< 5 x ULN if judged by the investigator to be related to liver metastases * Alkaline phosphatase \< 2.5 x ULN or \< 5 x ULN if judged by the investigator to be related to liver metastases Renal: * Serum creatinine \< 1.5 x ULN or Calculated creatinine clearance of \> 45 cc/min using the Cockcroft-Gault formula Cardiovascular: * No clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease \>2 (see SPM) within 3 months prior to registration for protocol therapy * No presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia. * No history of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is permitted.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
74
Helen F. Graham Cancer Center
Newark, Delaware, United States
Northwestern University Feinberg School of Medicine
Time to Disease Progression - Median Time to Progression and Log-Rank Test
Kaplan-Meier analysis comparing arm A to arm B. Median time to progression and log-rank test. Safety lead-in participants are not included in this analysis per protocol.
Time frame: 24 months
Percentage of Participants With Grade 3/4 Hematologic and Non-Hematologic Toxicities
Percentage of participants who experienced grade 3/4 hematologic and non-hematologic toxicities. Participants from Arm A were compared to subjects from Arm B + Safety Lead-In.
Time frame: 6 weeks (2 Cycles)
Measure the Response Rate (CR + PR) in Each Arm
Response assessments completed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST Therasse et al., 2000). Complete Response (CR) is defined as: Disappearance of all target lesions. Partial Response (PR) is defined as: \>=30% decrease in the sum of the longest diameter of target lesions.
Time frame: 24 months
Measure Disease Control Rate (CR + PR+ SD) in Each Arm
Response assessments completed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST Therasse et al., 2000). Complete Response (CR) is defined as: Disappearance of all target lesions. Partial Response (PR) is defined as: \>=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD) is defined as: neither a partial response or progressive disease ( \>=20% increase in the sum of the longest diameter of the target lesions).
Time frame: 24 months
Measure Overall Survival for Each Arm
Time frame: 24 months
Assess VEGF Polymorphisms and Correlate Subject Response
Time frame: 24 months
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ZD6474 100mg oral daily to be continued for the duration of the study.
Chicago, Illinois, United States
Medical & Surgical Specialists, LLC
Galesburg, Illinois, United States
Cancer Care Center of Southern Indiana
Bloomington, Indiana, United States
Oncology Hematology Associates of SW Indiana
Evansville, Indiana, United States
Fort Wayne Oncology & Hematology, Inc
Fort Wayne, Indiana, United States
IN Onc/Hem Associates
Indianapolis, Indiana, United States
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States
St. Vincent Hospital & Health Centers
Indianapolis, Indiana, United States
IU Health Arnett Cancer Center
Lafayette, Indiana, United States
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