Non-squamous Non-small Cell Lung Cancer
Conditions
Keywords
stage IV, stage IIIB, EGFR mutation, non-squamous, liquid biopsy, erlotinib, bevacizumab
Brief summary
The purpose of this study is to test whether the combination of bevacizumab and erlotinib can prolong progression free survival as compared with erlotinib alone as first-line treatment in patients with non small cell lung cancer (NSCLC) with activating mutation of EGFR.
Detailed description
The co-primary objectives are to assess investigator-assess, and blinded independent centrally-reviewed progression-free survival .
Interventions
DRUGErlotinib
given orally 150 mg daily
DRUGBevacizumab
15 mg/kg intravenously every 21 days.
Sponsors
National Cancer Institute, Naples
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years 2. Histological documentation of primary non squamous lung carcinoma 3. Stage IV or IIIB disease with supraclavicular metastatic nodes (according to TNM 7th edition) 4. Activating epidermal growth factor receptor mutation (exon19 deletion or exon 21 L858R mutation or other activating/sensitizing mutations, such as exon 21 L861Q, exon 18 G719S, G719A and G719C, exon 20 S768I and V769L). EGFR mutation testing must be performed at participating centres in a certified lab (AIOM-SIAPEC program or other European Quality Assurance \[EQA\] schemes) 5. Clinical or radiologic evidence of disease (at least one target or non target lesion according to RECIST 1.1) 6. ECOG performance status 0 to 2 7. Life expectancy \> 3 months 8. Use of an acceptable mean of contraception for men and women of childbearing potential 9. Written informed consent.
Exclusion criteria
1. EGFR T790M mutation alone or exon 20 insertions as unique mutation 2. Tumors with a squamous component 3. Prior chemotherapy or any other medical treatment for advanced NSCLC (previous neoadjuvant or adjuvant chemotherapy is allowed if \> 6 months before randomisation) 4. Radiotherapy to any site for any reason within 28 days prior to randomization (palliative radiotherapy to bone lesions is allowed if ≥ 14 days before randomization) 5. Full-dose anticoagulation with warfarin 6. Current or recent (within 10 days of enrolment) use of aspirin (\>325 mg/day) or chronic use of other full-dose nonsteroidal anti-inflammatory drugs (NSAIDs) with anti-platelet activity 7. Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4) are prohibited =\< 7 days prior to registration 8. Receiving any medications or substances that are inducers of CYP3A4 use of inducers are prohibited =\< 7 days prior to registration 9. Inadequate coagulation parameters: * activated partial thromboplastin time (APTT) \>1.5 x the upper limit of normal (ULN) or * INR \>1.5 10. Inadequate liver function, defined as: * serum (total) bilirubin \>1.5 x ULN * AST/SGOT or ALT/SGPT \>2.5 x ULN 11. Inadequate renal function, defined as: * serum creatinine \>2.0 mg/dl or \>177 micromol/l * urine dipstick for proteinuria \>2+. Patients with \> o = 1+ proteinuria at baseline dipstick analysis must undergo a 24-hour urine collection and must demonstrate ≤1g of protein in their 24-hour urine collection. 12. Pregnancy or breast-feeding 13. Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \>100 mmHg on antihypertensive medications) 14. History of gross hemoptysis within 3 months prior to randomization unless definitively treated with surgery or radiation 15. History of any of the following within 6 months prior to randomisation: serious systemic disease, unstable angina, New York Heart Association (NYHA) Grade 2 or greater Congestive Heart Failure (CHF), unstable symptomatic arrhythmia requiring medication, clinically significant peripheral vascular disease, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess 16. Serious, non-healing wound, ulcer, or bone fracture 17. Evidence of bleeding diathesis or coagulopathy or other serious or acute internal bleeding within 6 months prior to randomization 18. Central Nervous System (CNS) bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months 19. In-patient surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization 20. Minor surgical procedure, fine needle aspirations or core biopsy within 7 days prior to randomization 21. Anticipation of need for a major surgical procedure during the course of the study 22. Inability to take oral medication or requirement for intravenous (IV) alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption 23. Evidence of confusion or disorientation, or history of major psychiatric illness that may impair the patient's understanding of the Informed Consent Form or his/her ability to comply with study requirements 24. Any other invasive malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA) 25. Brain metastasis 26. Patients who have had radiotherapy ≥ 4 weeks prior to the first dose of study treatment, but who are still experiencing acute toxic effects of radiotherapy 27. Known HIV positive patients (patients with both acute or chronic infection are excluded) 28. Active HBV or HCV infection (patients with chronic non-active infection are eligible) 29. Any already known inflammatory changes of the surface of the eye at baseline 30. Any other concomitant pathologies or laboratory alterations that prevent or contraindicate the use of erlotinib or bevacizumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| progression free survival | up to 2 years | as determined by investigator |
Secondary
| Measure | Time frame |
|---|---|
| overall survival | 1 year |
| changes in quality of life scores from baseline | up to 2 years |
| number of patients with complete and partial responses , investigator assessed | 6 months |
| worst grade toxicity per patient | up to one year |
| progression free survival according to type of EGFR mutation (exon 19del, exon 21L858R, other) | 2 years |
| number of patients with complete and partial responses , centrally reviewed | 6 months |
Other
| Measure | Time frame | Description |
|---|---|---|
| number and type of EGFR mutations in plasma samples | up to 2 years | samples taken at baseline, 6 weeks, 6 months, and at progression |
Countries
Italy
Outcome results
None listed