Erlotinib + Bevacizumab for PS 2 Chemotherapy Naïve Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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The strategy for combining therapeutic agents in cancer treatments has been successful in multiple tumor types, including NSCLC. Erlotinib and bevacizumab target different pathways involved in tumor growth. Nonclinical studies have demonstrated that the combination of bevacizumab and erlotinib results in greater efficacy than either agent alone. Furthermore, because there is little to no overlap in toxicity profile between the two agents, the combination is expected to be well tolerated and may provide even greater benefit for patients who are unable to receive cytotoxic therapy.

Detailed Description
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OUTLINE: This is a multi-center study. Bevacizumab 15 mg/kg IV on day 1 Erlotinib 150 mg po qd days 1-21 Disease Assessment during even numbered cycles If no progressive disease observed, continue (combination or single agent- see below) until unacceptable toxicity or progressive disease. If progressive disease observed, treatment will be discontinued. Cycles will be repeated every 21 days up to a total of 6 cycles. Patients with non-progression after 6 cycles may stay on therapy (single agent erlotinib or the combination) until progressive disease or intolerable toxicity (at the physician discretion). Patients who require discontinuation of bevacizumab may receive at investigator's discretion erlotinib alone on study until progression. Patients who require discontinuation of erlotinib may receive at investigator's discretion bevacizumab alone until progression. ECOG Performance Status 2 Hematopoietic: Absolute neutrophil count (ANC) > 1,000 mm3 Platelet count > 100,000 mm3 Hemoglobin > 8 g/dl Hepatic: Bilirubin < 2 X upper limit of normal. Aspartate aminotransferase (AST, SGOT) < 2.5 X upper limit of normal or 5 X if liver involvement. Renal: Urine protein:creatinine ratio 1.0 at screening Cardiovascular: Blood pressure of < 150/100 mmHg. No history of unstable angina. No history of New York Heart Association (NYHA) Grade II or greater congestive heart failure. No history of myocardial infarction within 6 months prior to registration for protocol therapy. No history of stroke within 6 months prior to registration for protocol therapy. No clinically significant peripheral vascular disease.

Official Title
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A Phase II Study of Erlotinib With Bevacizumab in Chemotherapy Naïve Performance Status (PS) 2 Patients With Advanced Non-Small Cell Lung Cancer

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Erlotinib
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological proof of non-small cell lung cancer meeting one of the following criteria: stage III b with a pleural effusion stage IV Histology must not be squamous cell. No prior chemotherapy or hormonal therapy. Prior radiation therapy must be completed at least 21 days prior to being registered for protocol therapy. No prior use of an epidermal growth factor receptor (EGFR) inhibitor or antiangiogenic agent. No treatment with any investigational agent within 30 days prior to being registered for protocol therapy. Measurable disease according to RECIST and obtained by imaging within 28 days prior to being registered for protocol therapy. ECOG Performance Status of 2 in the opinion of the treating investigator. Age > 18 years at the time of consent. Females of childbearing potential and males must be willing to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) while on treatment and for a 6 week period thereafter. Females of childbearing potential must have a negative pregnancy test within 7 days prior to being registered for protocol therapy. Subjects are considered not of child bearing potential if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. Females must not be breastfeeding. Able to comply with study and/or follow-up procedures. Exclusion Criteria: Evidence of bleeding diathesis or coagulopathy. Evidence of central nervous system involvement or brain metastases confirmed by head CT or brain MRI within 28 days prior to being registered for protocol therapy. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration for protocol therapy. Anticipation of need for major surgical procedure during the course of the study. Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to registration for protocol therapy. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to registration for protocol therapy. Serious, non-healing wound, ulcer, or bone fracture. History of hemoptysis. Clinically significant infections as judged by the treating investigator. Other active malignancy

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: 1<br>Bevacizumab + erlotinib; if no progressive disease observed, combination or single-agent treatment will continue until unacceptable toxicity or progressive disease. | Drug: Erlotinib<br>* Erlotinib 150 mg qd days 1-21<br>Drug: Bevacizumab<br>* Bevacizumab 15 mg/kg IV, day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Establish Rate of Non-progressive Disease at 4 Months in Patients With Advanced NSCLC Who Have Been Designated PS2 by Their Treating Physician |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression |  | 12 months | 
| Overall Survival |  | 12 months |