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

NCT02633189 | Unknown Phase 3 DMC

• 2 other identifiers: BEVERLY2015-002235-17
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 55

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.

Conditions

Non-squamous Non-small Cell Lung Cancer

Keywords

stage IV; stage IIIB; EGFR mutation; non-squamous; liquid biopsy; erlotinib; bevacizumab

Outcome Measures

Primary Outcomes (2)

• progression free survival

  as determined by investigator

  up to 2 years

• progression free survival

  as determined by an independent central review board blinded to study treatment

  up to 2 years

Secondary Outcomes (6)

• 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

• number of patients with complete and partial responses , centrally reviewed

  6 months

• worst grade toxicity per patient

  up to one year

Other Outcomes (1)

• number and type of EGFR mutations in plasma samples

  up to 2 years

Study Arms (2)

erlotinib and bevacizumab

EXPERIMENTAL

Drug: Erlotinib; Drug: Bevacizumab

erlotinib

ACTIVE COMPARATOR

Drug: Erlotinib

Interventions

Erlotinib DRUG

given orally 150 mg daily

erlotinib; erlotinib and bevacizumab

Bevacizumab DRUG

15 mg/kg intravenously every 21 days.

erlotinib and bevacizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Cancer Institute, Naples: lead

Study Sites (55)

Ospedale Ramazzini, Day Hospital Oncologico

Carpi, MO, 41012, Italy

Location

Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico

Palermo, PA, 90146, Italy

Location

Ospedale di Prato

Prato, PO, 59100, Italy

Location

Ospedale S. Chiara

Trento, TN, 38100, Italy

Location

Ospedale S. Bortolo ULSS 6, U.O. di Oncologia Medica

Vicenza, VI, 36100, Italy

Location

A.S.O. SS Antonio e Biagio e Cesare Arrigo

Alessandria, Italy

Location

A.O. S. Giuseppe Moscati

Avellino, Italy

Location

Centro Riferimento Oncologico

Aviano, Italy

Location

AO G. Rummo

Benevento, Italy

Location

Ospedale Senatore Antonio Perrino

Brindisi, Italy

Location

Ospedale A. cardarelli

Campobasso, Italy

Location

U.L.S.S. 15 Veneto

Camposampiero, Italy

Location

A.O. Garibaldi Nesima

Catania, Italy

Location

Centro Clinico Diagnostico G.B. Morgagni

Catania, Italy

Location

Policlinico vittorio Emanuele

Catania, Italy

Location

Ospedale Civile per gli Infermi

Faenza, Italy

Location

Ospedale S. Croce

Fano, Italy

Location

A.O.U. Arcispedale Sant'Anna

Ferrara, Italy

Location

Ospedale Villa Scassi

Genova, Italy

Location

Ospedale di Guastalla

Guastalla, Italy

Location

A.O. Vito Fazzi

Lecce, Italy

Location

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

Meldola, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Istituto Nazionale Tumori

Milan, Italy

Location

Ospedale San Paolo

Milan, Italy

Location

A.O. U.L.S.S. 13

Mirano, Italy

Location

A.O.U. Policlinico Modena

Modena, Italy

Location

Azienda Ospedaliera Cardarelli

Napoli, 80131, Italy

Location

A.O.U. Seconda Università di Napoli

Napoli, Italy

Location

AORN Ospedale dei Colli - Osp Monaldi

Napoli, Italy

Location

Istituto Nazionale Tumori Fondazione G. Pascale

Napoli, Italy

Location

Istituto Sacro Cuore Don Calabria

Negrar, Italy

Location

A.O.U. Maggiore della Carità

Novara, Italy

Location

Istituto Oncologico Veneto

Padua, Italy

Location

Policlinico Giaccone

Palermo, Italy

Location

Fondazione Salvatore Maugeri

Pavia, Italy

Location

Osp. S. Maria della Misericordia

Perugia, Italy

Location

A.O. Ospedali Riuniti Marche Nord

Pesaro, Italy

Location

Ospedale Guglielmo da Saliceto

Piacenza, Italy

Location

A.O. San Carlo

Potenza, Italy

Location

Ospedale Santa Maria delle Croci - AUSL

Ravenna, Italy

Location

Ospedale Umberto I

Ravenna, Italy

Location

Ospedale degli Infermi Rimini - Ospedale Cervesi Cattolica

Rimini, Italy

Location

IRCCS Centro di Riferimento Oncologico Basilicata

Rionero in Vulture, Italy

Location

Istituto Regina Elena

Roma, Italy

Location

Ospedale Camillo Forlanini

Roma, Italy

Location

Ospedale S. Giovanni Calibita Fatebenefratelli

Roma, Italy

Location

Policlinico Universitario Campus Bio Medico

Roma, Italy

Location

Ospedale di Sondrio

Sondrio, Italy

Location

Ospedale Fabrizio Spaziani di Frosinone

Sora, Italy

Location

Ospedale Maggiore

Trieste, Italy

Location

Azienda Ospedaliero-Universitaria S.M. della Misericordia di Udine

Udine, Italy

Location

Ospedale S. Andrea

Vercelli, Italy

Location

A.O.U. Integrata

Verona, Italy

Location

ASL Viterbo - Ospedale Belcolle

Viterbo, Italy

Location

Related Publications (2)

• Piccirillo MC, Bonanno L, Garassino MC, Esposito G, Dazzi C, Cavanna L, Burgio MA, Rosetti F, Rizzato S, Morgillo F, Cinieri S, Veccia A, Papi M, Tonini G, Gebbia V, Ricciardi S, Pozzessere D, Ferro A, Proto C, Costanzo R, D'Arcangelo M, Proietto M, Gargiulo P, Di Liello R, Arenare L, De Marinis F, Crino L, Ciardiello F, Normanno N, Gallo C, Perrone F, Gridelli C, Morabito A. Addition of Bevacizumab to Erlotinib as First-Line Treatment of Patients With EGFR-Mutated Advanced Nonsquamous NSCLC: The BEVERLY Multicenter Randomized Phase 3 Trial. J Thorac Oncol. 2022 Sep;17(9):1086-1097. doi: 10.1016/j.jtho.2022.05.008. Epub 2022 Jun 1.

  PMID: 35659580 DERIVED

• Deng Z, Qin Y, Liu Y, Zhang Y, Lu Y. Role of Antiangiogenic Agents Combined With EGFR Tyrosine Kinase Inhibitors in Treatment-naive Lung Cancer: A Meta-Analysis. Clin Lung Cancer. 2021 Jan;22(1):e70-e83. doi: 10.1016/j.cllc.2020.08.005. Epub 2020 Sep 18.

  PMID: 33067126 DERIVED

MeSH Terms

Interventions

Erlotinib Hydrochloride; Bevacizumab

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Cesare Gridelli, M.D.

  S.G.Moscati Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 17, 2015
• Study Start: April 1, 2016
• Primary Completion: December 1, 2023
• Study Completion: July 1, 2024
• Last Updated: March 24, 2023

Record last verified: 2023-03

Locations

IT (55)