Phase II Trial of Bevacizumab in Combination With Gemcitabine and Carboplatin in Patients With Newly Diagnosed Non-Small Cell Lung Cancer (Excluding Squamous Cell Carcinoma)
- Advanced stage NSCLC (IIIB with malignant pleural effusion or stage IV) excluding
squamous cell histology, with measurable or evaluable disease.
- No prior systemic therapy for advanced NSCLC, prior therapy for early stage disease
with one regimen is acceptable if it was completed at least 6 months prior to study
- Palliative radiotherapy to painful bony metastases will be permitted prior to study
entry if completed prior to initiation of study treatment, and there are no residual
sequelae of therapy such as bone marrow suppression.
- Life expectancy of at least 3 months.
- ECOG Performance status 0-1.
- Age 18 or higher.
- Willingness to use appropriate contraception to avoid pregnancy during the study
(female patient or female partner of a male patient)
- Patients must have normal organ and marrow function as defined below:
- leukocytes >= 3,000/µl
- absolute neutrophil count >= 1,500/µl
- platelets >= 100,000/µl
- total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) <= 2.5 x institutional upper limit of normal
- creatinine within normal institutional limits OR creatinine clearance >= 60
mL/min/1.73 m2 for patients with creatinine levels above institutional normal
- Ability to sign informed consent.
- Prior systemic treatment for advanced NSCLC. One prior regimen (up to 4 cycles) of
neoadjuvant or adjuvant therapy for early stage disease will be allowed if completed
at least 6 months prior to study entry.
- Known brain metastases.
- Prior treatment with bevacizumab.
- History of allergic reactions or sensitivity attributed to compounds of similar
chemical or biologic composition to bevacizumab.
- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in any other experimental drug study.
- Concomitant chemotherapy, radiotherapy or investigational agents.
- Evidence of bleeding diathesis or coagulopathy.
- Use of anti-coagulant agents including warfarin, heparin, aspirin, NSAIDs.
- Pregnant (positive pregnancy test) or lactating women.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, anticipation of need for major surgical procedure during the course
of the study.
- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to day 0.
- Urine protein:creatinine ratio >= 1.0 at screening.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to Day 0.
- Serious, non-healing wound, ulcer, or bone fracture.
- Lung carcinoma of squamous cell histology or any histology in close proximity to a
major vessel, or with significant cavitation as assessed by treating investigator in
consultation with an attending radiologist.
- History of hemoptysis (bright red blood of 1/2 teaspoon or more).
- Significant co-morbidities including:
- Blood pressure of >150/100 mmHg
- Unstable angina
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- History of myocardial infarction within 6 months
- History of stroke within 6 months
- Clinically significant peripheral vascular disease
- Psychiatric illness/social situations that would limit compliance with study
- Another active malignancy except for non-melanoma skin cancers.
- Inability to comply with study and/or follow-up procedures.