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)

March 23, 2023 updated by: National Cancer Institute, Naples

A Randomized Open-label Phase 3 Trial Comparing Bevacizumab + Erlotinib vs Erlotinib Alone as First Line Treatment of Patients With EGFR Mutated Advanced Non Squamous Non Small Cell Lung Cancer

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.

Study Overview

Status

Active, not recruiting

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Alessandria, Italy
        • A.S.O. SS Antonio e Biagio e Cesare Arrigo
      • Avellino, Italy
        • A.O. S. Giuseppe Moscati
      • Aviano, Italy
        • Centro Riferimento Oncologico
      • Benevento, Italy
        • AO G. Rummo
      • Brindisi, Italy
        • Ospedale Senatore Antonio Perrino
      • Campobasso, Italy
        • Ospedale A. cardarelli
      • Camposampiero, Italy
        • U.L.S.S. 15 Veneto
      • Catania, Italy
        • Policlinico Vittorio Emanuele
      • Catania, Italy
        • A.O. Garibaldi Nesima
      • Catania, Italy
        • Centro Clinico Diagnostico G.B. Morgagni
      • Faenza, Italy
        • Ospedale Civile per gli Infermi
      • Fano, Italy
        • Ospedale S. Croce
      • Ferrara, Italy
        • A.O.U. Arcispedale Sant'Anna
      • Genova, Italy
        • Ospedale Villa Scassi
      • Guastalla, Italy
        • Ospedale di Guastalla
      • Lecce, Italy
        • A.O. Vito Fazzi
      • Meldola, Italy
        • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      • Milano, Italy
        • Istituto Europeo di Oncologia
      • Milano, Italy
        • Istituto Nazionale Tumori
      • Milano, Italy
        • Ospedale San Paolo
      • Mirano, Italy
        • A.O. U.L.S.S. 13
      • Modena, Italy
        • A.O.U. Policlinico Modena
      • Napoli, Italy
        • A.O.U. Seconda Universita di Napoli
      • Napoli, Italy
        • Istituto Nazionale Tumori Fondazione G. Pascale
      • Napoli, Italy, 80131
        • Azienda Ospedaliera Cardarelli
      • Napoli, Italy
        • AORN Ospedale dei Colli - Osp Monaldi
      • Negrar, Italy
        • Istituto Sacro Cuore Don Calabria
      • Novara, Italy
        • A.O.U. Maggiore della Carità
      • Padova, Italy
        • Istituto Oncologico Veneto
      • Palermo, Italy
        • Policlinico Giaccone
      • Pavia, Italy
        • Fondazione Salvatore Maugeri
      • Perugia, Italy
        • Osp. S. Maria Della Misericordia
      • Pesaro, Italy
        • A.O. Ospedali Riuniti Marche Nord
      • Piacenza, Italy
        • Ospedale Guglielmo da Saliceto
      • Potenza, Italy
        • A.O. San Carlo
      • Ravenna, Italy
        • Ospedale Umberto I
      • Ravenna, Italy
        • Ospedale Santa Maria delle Croci - AUSL
      • Rimini, Italy
        • Ospedale degli Infermi Rimini - Ospedale Cervesi Cattolica
      • Rionero in Vulture, Italy
        • IRCCS Centro di Riferimento Oncologico Basilicata
      • Roma, Italy
        • Istituto Regina Elena
      • Roma, Italy
        • Ospedale S. Giovanni Calibita Fatebenefratelli
      • Roma, Italy
        • Ospedale Camillo Forlanini
      • Roma, Italy
        • Policlinico Universitario Campus Bio Medico
      • Sondrio, Italy
        • Ospedale di Sondrio
      • Sora, Italy
        • Ospedale Fabrizio Spaziani di Frosinone
      • Trieste, Italy
        • Ospedale Maggiore
      • Udine, Italy
        • Azienda Ospedaliero-Universitaria S.M. della Misericordia di Udine
      • Vercelli, Italy
        • Ospedale S. Andrea
      • Verona, Italy
        • A.O.U. Integrata
      • Viterbo, Italy
        • ASL Viterbo - Ospedale Belcolle
    • MO
      • Carpi, MO, Italy, 41012
        • Ospedale Ramazzini, Day Hospital Oncologico
    • PA
      • Palermo, PA, Italy, 90146
        • Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico
    • PO
      • Prato, PO, Italy, 59100
        • Ospedale di Prato
    • TN
      • Trento, TN, Italy, 38100
        • Ospedale S. Chiara
    • VI
      • Vicenza, VI, Italy, 36100
        • Ospedale S. Bortolo ULSS 6, U.O. di Oncologia Medica

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: erlotinib
given orally 150 mg daily
Experimental: erlotinib and bevacizumab
given orally 150 mg daily
15 mg/kg intravenously every 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
progression free survival
Time Frame: up to 2 years
as determined by investigator
up to 2 years
progression free survival
Time Frame: up to 2 years
as determined by an independent central review board blinded to study treatment
up to 2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
overall survival
Time Frame: 1 year
1 year
changes in quality of life scores from baseline
Time Frame: up to 2 years
up to 2 years
number of patients with complete and partial responses , investigator assessed
Time Frame: 6 months
6 months
number of patients with complete and partial responses , centrally reviewed
Time Frame: 6 months
6 months
worst grade toxicity per patient
Time Frame: up to one year
up to one year
progression free survival according to type of EGFR mutation (exon 19del, exon 21L858R, other)
Time Frame: 2 years
2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
number and type of EGFR mutations in plasma samples
Time Frame: up to 2 years
samples taken at baseline, 6 weeks, 6 months, and at progression
up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Cesare Gridelli, M.D., S.G.Moscati Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2016

Primary Completion (Anticipated)

December 1, 2023

Study Completion (Anticipated)

July 1, 2024

Study Registration Dates

First Submitted

December 15, 2015

First Submitted That Met QC Criteria

December 15, 2015

First Posted (Estimate)

December 17, 2015

Study Record Updates

Last Update Posted (Actual)

March 24, 2023

Last Update Submitted That Met QC Criteria

March 23, 2023

Last Verified

March 1, 2023

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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