Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This randomized phase II trial is studying cisplatin and etoposide phosphate to see how well they work when given with or without GDC-0449 or cixutumumab in treating patients with extensive-stage small cell lung cancer. Drugs used in chemotherapy, such as cisplatin and etoposide phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. GDC-0449 may slow the growth of tumor cells. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving cisplatin and etoposide are more effective when given together with GDC-0449 or cixutumumab in treating small cell lung cancer

Further Study Information

PRIMARY OBJECTIVES:

I. To evaluate the progression-free survival of patients with extensive stage small cell lung cancer treated with cisplatin and etoposide with or without Hedgehog antagonist GDC-0449 or cixutumumab.

SECONDARY OBJECTIVES:

I. To evaluate the response rate in patients treated with these regimens. II. To evaluate the overall survival of patients treated with these regimens. III. To evaluate the toxicity of these regimens in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to gender. Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive cisplatin IV over 1-2 hours on day 1 and etoposide phosphate IV over 1-2 hours on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive cisplatin and etoposide phosphate as in arm I and oral Hedgehog antagonist GDC-0449 once daily on days 1-21. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive Hedgehog antagonist GDC-0449 alone once daily in the absence of disease progression or unacceptable toxicity.

ARM III: Patients receive cisplatin and etoposide phosphate as in arm I and cixutumumab IV over 1 hour on days 1, 8, and 15. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive cixutumumab alone once weekly in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.

Eligibility Criteria

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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Chandra Belani

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00887159
Information obtained from ClinicalTrials.gov on December 03, 2012

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