Bevacizumab, Cisplatin, Etoposide, and Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and help kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving bevacizumab together with cisplatin, etoposide, and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with cisplatin, etoposide, and radiation therapy works in treating patients with limited-stage small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the 1-year progression-free survival of patients with limited-stage small cell lung cancer treated with bevacizumab, cisplatin, etoposide, and radiotherapy. Secondary Determine the toxicity of this regimen in these patients. Determine the response rate in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive cisplatin IV over 30-60 minutes and bevacizumab IV over 30-90 minutes on day 1 and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. During course 1, patients also undergo thoracic radiotherapy twice daily on days 1-5, 8-12, and 15-19. Patients achieving a complete or partial response or stable disease after the first 4 courses of chemotherapy continue to receive bevacizumab IV over 30-90 minutes on day 1. Treatment with bevacizumab repeats every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Within 4-6 weeks after blood counts recover from the first 4 courses of chemotherapy, patients achieving a complete or partial response also undergo prophylactic cranial irradiation (PCI) in 10 fractions over 3 weeks.* NOTE: *Bevacizumab should not be given for 3 weeks prior to or during PCI, but resumed 1 week after completion of PCI. After completion of study treatment, patients are followed periodically for 10 years. PROJECTED ACCRUAL: A total of 79 patients will be accrued for this study.

Official Title
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Phase II Trial of Bevacizumab in Combination With Cisplatin/Etoposide and Twice Daily Radiation for Patients With Limited-Stage Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: cisplatin
* Drug: etoposide
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed small cell lung cancer (SCLC) Limited-stage disease, defined as SCLC confined to ≥ 1 of the following: One hemithorax Ipsilateral supraclavicular fossa Measurable disease No malignant pleural effusion, contralateral hilar disease, or contralateral supraclavicular disease Minimal pleural effusion visible on CT scan of the chest, but not evident on chest x-ray, allowed No completely surgically resected disease No CNS disease, including primary brain tumor or brain metastasis PATIENT CHARACTERISTICS: ECOG performance status 0-2 Absolute granulocyte count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Bilirubin ≤ 1.5 mg/dL Creatinine ≤ 1.5 mg/dL Urine protein:creatinine ratio ≤ 0.5 OR 24-hour urine protein < 1,000 mg Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment INR ≤ 1.5 (unless on full-dose anticoagulants) No active serious infection No serious or nonhealing wound No ulcer or bone fracture No evidence of bleeding diatheses or coagulopathy No hemoptysis No known hypersensitivity to Chinese hamster ovary cell products and/or other recombinant human antibodies No clinically significant cardiovascular disease, including any of the following: Uncontrolled hypertension New York Heart Association class II-IV congestive heart failure Serious cardiac arrhythmia requiring medication Unstable angina pectoris Symptomatic peripheral vascular disease Cerebrovascular accident within the past 6 months Symptomatic heart disease within the past 6 months Myocardial infarction within the past 6 months Unstable angina within the past 6 months No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 4 weeks No significant traumatic injury within the past 4 weeks PRIOR CONCURRENT THERAPY: At least 4 weeks since prior major surgery or open biopsy At least 1 week since prior core biopsy No prior chemotherapy or radiotherapy for small cell lung cancer No concurrent major surgery No concurrent palliative local radiotherapy No concurrent intensity-modulated radiotherapy Concurrent full-dose anticoagulants (e.g., warfarin) allowed provided all of the following criteria are met: INR ≤ 3 In-range INR (2-3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bevacizumab|nan|
|Drug: cisplatin|nan|
|Drug: etoposide|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival at 1 year |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate |  |  | 
| Toxicity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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limited stage small cell lung cancer