Pemetrexed Disodium and Bevacizumab in Treating Patients With Stage III or Stage IV Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving pemetrexed disodium together with bevacizumab may be an effective treatment for non-small cell lung cancer. PURPOSE: This phase II trial is studying how well giving pemetrexed disodium together with bevacizumab works in treating patients with stage III or stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Assess the 3 month progression-free survival rate of the combination of pemetrexed disodium with bevacizumab in a patient population with stage IIIB (due to pleural effusion) or IV non-small cell lung cancer. Secondary Determine the tumor response rate in these patients. Determine the effect of pemetrexed disodium in combination with bevacizumab on overall survival and duration of response in these patients. Determine the toxicity profile of this drug regimen in these patients. OUTLINE: This is an open-label, multicenter study. Patients receive pemetrexed disodium IV over 10 minutes and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 5 years.

Official Title
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A Phase II Study of Pemetrexed Disodium (ALIMTA®) Plus Bevacizumab in Patients With Stage IIIB Pleural Effusion or Stage IV Non-Small Cell Lung Cancer (Second-Line Treatment)

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: pemetrexed disodium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically diagnosed stage IIIB or IV non-small cell lung cancer Stage IIIB patients must have pleural effusion No symptomatic serosal effusion (grade 2 dyspnea) that is not amenable to drainage Mixed histology allowed if all components consistent with non-small cell lung cancer Tumors with squamous cell histology feature are allowed Must have measurable disease with at least one lesion with a longest diameter accurately measured as ≥ 2.0 cm with conventional techniques or as ≥ 1.0 cm with spiral CT Large ( > 4 cm) centrally located lesions or large lesions in close proximity to major blood vessels should receive palliative radiation The irradiated lesion should not be a target lesion Previously treated with one chemotherapy regimen in the neoadjuvant, adjuvant, or advanced disease setting No symptomatic, untreated, or uncontrolled CNS metastases CNS metastases treated with prior whole brain radiotherapy allowed PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy ≥ 12 weeks Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/ mm^3 Hemoglobin ≥ 9 g/dL Bilirubin ≤ 1.5 times upper limit of normal (ULN) or direct bilirubin normal AST and ALT ≤ 3 times ULN (5 times ULN if liver has tumor involvement) Creatinine clearance ≥ 45 mL/min Urine protein:creatinine ratio < 1.0 Pregnant or nursing women are ineligible Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study participation No seizure disorder No clinically significant infection No other second primary malignancy within the past 5 years except carcinoma in situ of the cervix, non-melanomatous skin cancer, or low-grade (Gleason score ≤ 6) localized prostate cancer No hypertension or labile hypertension No history of poor compliance with antihypertensive medications No angina pectoris No congestive heart failure within the past 3 months unless ejection fraction > 40% No myocardial infarction within the past 6 months No cardiac arrhythmia No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung No active or recent history of hemoptysis Hemoptysis resolved > 2 weeks ago with measures such as palliative radiation therapy (i.e., 3,000 cGy over 10 fractions), arteriographic embolization, or endobronchial interventions (e.g., photodynamic therapy or brachytherapy) is acceptable No diabetes No prior serious, non-healing wounds, ulcers, or bone fractures No history of stroke within the past 6 months No history of abdominal fistula or gastrointestinal perforation No intra-abdominal abscess within the past 6 months Not at greater than average risk of bleeding No significant traumatic injury within the past 4 weeks PRIOR CONCURRENT THERAPY: No aspirin at doses ≥ 1.3 grams per day within 10 days prior to or 10 days after pemetrexed disodium treatment No chemotherapy within the past 3 weeks (6 weeks for mitomycin C or nitrosoureas) No immunotherapy or biologic therapy within the past 2 weeks No full field radiation therapy within the past 4 weeks or limited field radiation therapy within the past 2 weeks The site of previous radiotherapy should have evidence of progressive disease if it is the only site of disease No prior post pelvic radiation No prior use of pemetrexed disodium No prior radiation to > 25% of the marrow cavity No major surgery (i.e., laparotomy) or open biopsy within the past 4 weeks No minor surgery within the past 2 weeks except insertion of a vascular access device No concurrent major surgery No other chemotherapy, immunotherapy, hormonal therapy, radiotherapy, or any ancillary therapy considered investigational within the past 4 weeks No concurrent use of Hypericum perforatum (St. John's wort) No concurrent anticoagulant use Low-dose warfarin or heparin for deep venous thrombosis prophylaxis allowed

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: pemetrexed + bevacizumab<br>Patients receive pemetrexed disodium IV over 10 minutes and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 5 years. | Biological: bevacizumab<br> <br> Drug: pemetrexed disodium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of progression-free patients at 3 months |  | at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response (complete and partial) as assessed by RECIST criteria |  | Up to 5 years | 
| Overall survival |  | Up to 5 years | 
| Progression-free survival |  | Up to 5 years | 
| Duration of response |  | Up to 5 years | 
| Time to treatment failure |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent non-small cell lung cancer, squamous cell lung cancer, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer