A Randomized Phase II Study of Cisplatin and Etoposide in Combination With Either Hedgehog Inhibitor GDC-0449 or IGF-1R MOAB IMCA12 for Patients With Extensive Stage Small Cell Lung Cancer

Inclusion Criteria:

- Histologically or cytologically confirmed small cell lung cancer (SCLC)

- Extensive stage disease, as defined by any of the following criteria:

- Extrathoracic metastatic disease

- Malignant pleural effusion

- Bilateral or contralateral supraclavicular adenopathy

- Measurable disease based on RECIST criteria

- CNS metastases allowed provided the patient has completed a course of CNS
radiotherapy and has stable neurologic function for ≥ 28 days prior to randomization

- Prophylactic cranial irradiation allowed in those who have a response (in the
absence of progressive disease)

- ECOG performance status 0-1

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Leukocyte count ≥ 3,000/mm^3

- Hemoglobin ≥ 9 g/dL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

- AST/ALT ≤ 3 times ULN (≤ 5 times ULN if elevations are due to liver metastases)

- Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min

- Fasting serum glucose < 120 mg/dL

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective double-method contraception for ≥ 28 days before,
during, and for ≥ 12 months after completion of study treatment

- No concurrent uncontrolled illness including, but not limited to, any of the
following:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Uncontrolled cardiac arrhythmia

- Psychiatric illness or social situation that would limit compliance with study
requirements

- No poorly controlled diabetes mellitus

- History of diabetes mellitus allowed provided blood glucose is normal and the
patient is on a stable dietary or therapeutic regimen

- No history of allergic reactions attributed to compounds of similar chemical or
biological composition to Hedgehog antagonist GDC-0449, cixutumumab, or other study
agents

- No concurrent combination antiretroviral therapy for HIV-positive patients

- No prior chemotherapy or biologic therapy for SCLC

- No prior therapy with other agents targeting the IGFR or the Hedgehog signaling
pathway

- No prior irradiation to the only site of measurable or evaluable disease unless that
site had subsequent evidence of progression

- Prior palliative radiotherapy to other sites of disease allowed

- More than 14 days since prior radiotherapy (28 days for radiotherapy to the CNS) and
recovered

- More than 4 weeks since prior major surgery or hormonal therapy (other than
replacement therapy) and recovered

- No other concurrent investigational or anticancer agents