Study Comparing Bevacizumab + Erlotinib vs Erlotinib Alone as First Line Treatment of Patients With EGFR Mutated Advanced Non Squamous Non Small Cell Lung Cancer (BEVERLY)

National Cancer Institute, Naples

Status and phase

Active, not recruiting

Phase 3

Conditions

Non-squamous Non-small Cell Lung Cancer

Treatments

Drug: Bevacizumab

Drug: Erlotinib

Study type

Interventional

Funder types

Other

Identifiers

NCT02633189

2015-002235-17 (EudraCT Number)

BEVERLY

Details and patient eligibility

About

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.

Full description

The co-primary objectives are to assess investigator-assess, and blinded independent centrally-reviewed progression-free survival .

Enrollment

200 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age ≥18 years
Histological documentation of primary non squamous lung carcinoma
Stage IV or IIIB disease with supraclavicular metastatic nodes (according to TNM 7th edition)
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)
Clinical or radiologic evidence of disease (at least one target or non target lesion according to RECIST 1.1)
ECOG performance status 0 to 2
Life expectancy > 3 months
Use of an acceptable mean of contraception for men and women of childbearing potential
Written informed consent.

Exclusion criteria

EGFR T790M mutation alone or exon 20 insertions as unique mutation
Tumors with a squamous component
Prior chemotherapy or any other medical treatment for advanced NSCLC (previous neoadjuvant or adjuvant chemotherapy is allowed if > 6 months before randomisation)
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)
Full-dose anticoagulation with warfarin
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
Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4) are prohibited =< 7 days prior to registration
Receiving any medications or substances that are inducers of CYP3A4 use of inducers are prohibited =< 7 days prior to registration
Inadequate coagulation parameters:
- activated partial thromboplastin time (APTT) >1.5 x the upper limit of normal (ULN) or
- INR >1.5
Inadequate liver function, defined as:
- serum (total) bilirubin >1.5 x ULN
- AST/SGOT or ALT/SGPT >2.5 x ULN
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.
Pregnancy or breast-feeding
Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure >100 mmHg on antihypertensive medications)
History of gross hemoptysis within 3 months prior to randomization unless definitively treated with surgery or radiation
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
Serious, non-healing wound, ulcer, or bone fracture
Evidence of bleeding diathesis or coagulopathy or other serious or acute internal bleeding within 6 months prior to randomization
Central Nervous System (CNS) bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months
In-patient surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization
Minor surgical procedure, fine needle aspirations or core biopsy within 7 days prior to randomization
Anticipation of need for a major surgical procedure during the course of the study
Inability to take oral medication or requirement for intravenous (IV) alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption
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
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)
Brain metastasis
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
Known HIV positive patients (patients with both acute or chronic infection are excluded)
Active HBV or HCV infection (patients with chronic non-active infection are eligible)
Any already known inflammatory changes of the surface of the eye at baseline
Any other concomitant pathologies or laboratory alterations that prevent or contraindicate the use of erlotinib or bevacizumab.