Clinical trial NCT00613626
Conditions: Small Cell Lung Cancer
Keywords: Extensive Stage Untreated
Sponsor: Hoosier Cancer Research Network
Start date: 2008-01-01; Completion date: 2015-08-01
Enrollment: 74 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 matched placebo oral daily to be continued for the duration of the study. Prophylactic antiemetics will be given at the discretion of the treating investigator. arm 2: Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 100mg oral daily to be continued for the duration of the study. Prophylactic antiemetics will be given at the discretion of the treating investigator. arm 3: Subjects will receive cisplatin 60 mg/m2 IV day 1 plus etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles plus ZD6474 100mg oral daily to be continued for the duration of the study. Prophylactic antiemetics will be given at the discretion of the treating investigator. The safety lead-in will be conducted to determine the safety of the combination of ZD6474 and cisplation + etopiside. If this combination is found to be unsafe, no patients will be randomized in the Phase II portion of the trial. If the combination is deemed safe according to the protocol, participants from the safety lead-in cohort will not be included in the efficacy analysis.
Interventions: intervention 1: Cisplatin intervention 2: Etoposide intervention 3: Placebo intervention 4: ZD6474
Intervention descriptions: intervention 1: Cisplatin 60 mg/m2 IV day 1 every 21 days for a total of 4 cycles intervention 2: Etoposide 120 mg/m2 IV days 1, 2, and 3 every 21 days for a total of 4 cycles intervention 3: Matched placebo oral daily intervention 4: ZD6474 100mg oral daily to be continued for the duration of the study.

Protocol documents: