Osimertinib and Bevacizumab as Treatment for EGFR-mutant Lung Cancers

Launched by MEMORIAL SLOAN KETTERING CANCER CENTER · Jun 14, 2016

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Eligibility criteria

• Inclusion Criteria:
• • Written informed consent
• • Advanced biopsy-proven metastatic non-small cell lung cancer
• • Somatic activating mutation in EGFR
• • No prior treatment with an EGFR TKI
• • No prior treatment with a VEGF inhibitor
• • Measurable (RECIST 1.1) indicator lesion not previously irradiated
• • Karnofsky performance status (KPS) ≥ 70%
• • Age \>18 years old
• • Adequate organ function
• • AST, ALT ≤ 3 x ULN
• • Total bilirubin ≤ 1.5x ULN
• • Creatinine ≤ 1.5x ULN OR calculated creatinine clearance \> 60ml/min
• • Absolute neutrophil count (ANC) ≥ 1000 cells/mm3
• • Hemoglobin≥8.0 g/dL
• • Platelets ≥100,000/mm3
• Exclusion Criteria:
• • Any contra-indications to bevacizumab which include but are not limited to recent
• • 1. Any previous venous thromboembolism \> NCI CTCAE Grade 3
• • 2. Severe uncontrolled hypertension (systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥ 100mmHg)
• • 3. Cardiovascular disease including stroke of myocardial infarction \<6 months prior to study enrollment, New York Heart Association Grade 2 or greater congestive heart failure, serious cardiac arrythmia uncontrolled by medication
• • 4. Hemorrhagic brain metastases. Asymptomatic (not requiring escalating doses of steroids) brain metastases are acceptable.
• • 5. History of severe proteinuria (urine dipstick ≥ 2+ or 24 hr urine \> 2gm/24hr)
• • 6. Prior history of hypertensive crisis or hypertensive encephalopathy
• • 7. History of a central nervous system disease (e.g. seizures) unrelated to cancer unless adequately treated with standard medical therapy
• • 8. Significant vascular disease (e.g. aortic aneurysm requiring surgical repair)≥ 6 months prior to study enrollment
• • 9. History of hemoptysis (≥1/2 teaspoon of bright red blood per episode) within the last 3 months
• • 10. Evidence of a bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
• • 11. Current or recent (within 10 days of study drug start) use of aspirin (\>325mg daily), clopidogrel (\>75mg daily).
• • 12. Recent initiation of full dose oral or parental anticoagulants that have not been in place for at least 2 weeks.
• • 13. Tumor invading or abutting major blood vessels
• • 14. Tumor histology classified by squamous cell histology.
• • 15. Any history of abdominal fistula or GI perforation within 6 months of study enrollment
• • Pregnant or lactating women
• • Any type of systemic anticancer therapy (chemotherapy or experimental drugs) within 2 weeks of starting treatment on protocol
• • Any radiotherapy within 1 week of starting treatment on protocol
• • Any major surgery within 4 weeks of starting treatment on protocol
• • Any evidence of clinically significant interstitial lung disease
• • Known hypersensitivity to any component of bevacizumab and osimertinib