Bevacizumab, Docetaxel, and Gemcitabine Patients With Stage IIIB, Stage IV, or Recurrent Non-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 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. Drugs used in chemotherapy, such as docetaxel and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with docetaxel and gemcitabine hydrochloride may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving bevacizumab together with docetaxel and gemcitabine hydrochloride works in treating patients with stage IIIB, stage IV, or recurrent non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Estimate the 1-year progression-free survival rate in patients with stage IIIB, stage IV, or recurrent non-squamous cell non-small cell lung cancer treated with bevacizumab, docetaxel, and gemcitabine hydrochloride. Secondary Evaluate the median time to progression in patients treated with this regimen. Estimate the response rate in patients treated with this regimen. Determine the median overall survival of patients treated with this regimen. Determine the incidence of adverse events associated with this regimen in these patients. OUTLINE: Patients receive bevacizumab IV over 30-90 minutes and docetaxel IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with responsive or stable disease may then continue to receive bevacizumab alone for up to 12 months in the absence of disease progression. After completion of study treatment, patients are followed up every 3 months.

Official Title
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A Phase II Study of Bevacizumab Plus Docetaxel and Gemcitabine in Subjects With Advanced, Previously Untreated, Non-Squamous Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: docetaxel
* Drug: gemcitabine hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed non-squamous cell non-small cell lung cancer Stage IIIB (with pleural effusion), stage IV, or recurrent disease Bidimensionally measurable disease No known CNS disease, except for previously treated brain metastasis defined as no evidence of progression or hemorrhage after treatment AND no ongoing requirement for dexamethasone as documented by clinical examination, MRI, or CT scan Treatment for brain metastases may have included whole brain radiotherapy, radiosurgery (gamma knife, LINAC, or equivalent), or a combination of therapy as deemed appropriate by the treating physician Stable dose of anticonvulsants allowed No known metastatic disease to the gastrointestinal tract (e.g., stomach, small bowel, or large bowel) PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy > 3 months ANC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL Bilirubin ≤ 2.0 mg/dL AST or ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times ULN if hepatic metastases are present) Serum creatinine ≤ 1.8 mg/dL Urine protein:creatinine ratio < 1.0 OR proteinuria < 2+ by urine dipstick OR ≤ 1 g of protein by 24-hour urine collection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Available for regular follow-ups No inadequately controlled hypertension, defined as systolic BP > 150 mm Hg and/or diastolic BP > 100 mm Hg despite antihypertensive medications No history of hypertensive crisis or hypertensive encephalopathy No NYHA class II-IV congestive heart failure No myocardial infarction or unstable angina within the past 6 months No stroke or transient ischemic attack within the past 6 months No significant vascular disease (e.g., aortic aneurysm, aortic dissection requiring surgical repair, or recent peripheral arterial thrombosis) within the past 6 months No symptomatic peripheral vascular disease No evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation) No history of colonic diverticular disease (i.e., diverticulosis or diverticulitis) No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months No serious, nonhealing wound, ulcer, or bone fracture No known hypersensitivity to any component of bevacizumab No hemoptysis (bright red blood of ≥ ½ teaspoon per episode) within the past 3 months No significant traumatic injury within the past 28 days PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemotherapy or biological therapy No prior radiotherapy to an area of measurable disease unless there is documented progressive disease after completion of therapy More than 2 weeks since prior radiotherapy More than 4 weeks since prior and no concurrent participation in another experimental drug study, except for a Genentech-sponsored bevacizumab cancer study More than 28 days since prior major surgical procedure or open biopsy More than 3 months since prior abdominal surgery More than 3 months since prior neurosurgical resection or brain biopsy More than 7 days since prior core biopsy or other minor surgical procedure, except placement of a vascular access device No concurrent major surgical procedure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Bevacizumab, Docetaxel, and Gemcitabine<br>Treatment repeats every 21 days for up to 6 courses. | Biological: bevacizumab<br>* 15 mg/kg on day 1 of a 21-day cycle<br>Drug: docetaxel<br>* 75 mg/m2 on day 1<br>Drug: gemcitabine hydrochloride<br>* 900 mg/m2 on days 1, and 8,<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival(PFS) | PFS is defined as time to death or first occurrence of documented disease progression assessed by the investigator as per the RECIST guidelines (at lease a 20% increase in the diameter of a lesion, in addition to an absolute increase of 5mm). If no deaths occur prior to progression, this measure will be the same as the median time to progression. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time to Progression | Time to progression (TTP) is defined as the time from start of treatment to first evidence of disease progression, defined per the RECIST 1.1 criteria as at least a 20% increase in the diameter of a lesion and an absolute increase of at least 5mm. | 1 year | 
| Best Response | The number of patients with a response will be assessed using the RECIST criteria of complete response (the disappearance of all target lesions); partial response (at least a 30% decrease in the diameter of lesions); progressive disease at least a 20% increase in the diameter of lesions); or stable disease(neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease) | 1 year | 

 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, stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer, large cell lung cancer