Combination of the Hedgehog Inhibitor, LDE225, With Etoposide and Cisplatin in the First-Line Treatment of Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC)

In a standard, 3 + 3 dose escalation phase, two successive cohorts of ES-SCLC patients will receive LDE225 with etoposide and cisplatin with a dose of 200 mg to be reserved for de-escalation until the MTD is determined. Cohorts of at least 3 evaluable patients will be treated at each dose level of LDE225 (400 mg daily and 800 mg daily). One additional dose (200 mg daily) will be reserved for de-escalation. A minimum of 6 evaluable patients must be treated at the dose declared to be the MTD. Each cohort will consist of newly enrolled patients. An estimated total of 6 to 12 patients may be necessary to establish the MTD. Actual accrual will depend on the dose levels tested and the DLT observed. Upon completion of a minimum of four and a maximum of six cycles of LDE225 with etoposide and cisplatin, patients in each cohort with at least stable disease will receive maintenance LDE225 until disease progression or unacceptable toxicity.