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Non-squamous Non-small Cell Lung CancerPhase 3BEVERLYNCT02633189

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

A Phase 3 study testing Erlotinib and Bevacizumab in people with Non-squamous Non-small Cell Lung Cancer, run by National Cancer Institute, Naples at 55 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Non-squamous Non-small Cell Lung Cancer
What is being tested?
Erlotinib and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
55 sitesItaly
Study dates
Apr 2016to Jul 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • Life expectancy > 3 months
  • Use of an acceptable mean of contraception for men and women of childbearing potential
  • Written informed consent.

Who cannot join

  • 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
Show all 36Show fewer
  • 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.

Trial locations and contacts

55 sites in 1 country.

55 sites in 1 country

Italy55 sites

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

    Alessandria

  • A.O. S. Giuseppe Moscati

    Avellino

  • Centro Riferimento Oncologico

    Aviano

  • AO G. Rummo

    Benevento

  • Ospedale Senatore Antonio Perrino

    Brindisi

  • Ospedale A. cardarelli

    Campobasso

  • U.L.S.S. 15 Veneto

    Camposampiero

  • Ospedale Ramazzini, Day Hospital Oncologico

    Carpi, MO, 41012

  • A.O. Garibaldi Nesima

    Catania

  • Centro Clinico Diagnostico G.B. Morgagni

    Catania

  • Policlinico vittorio Emanuele

    Catania

  • Ospedale Civile per gli Infermi

    Faenza

  • Ospedale S. Croce

    Fano

  • A.O.U. Arcispedale Sant'Anna

    Ferrara

  • Ospedale Villa Scassi

    Genova

  • Ospedale di Guastalla

    Guastalla

  • A.O. Vito Fazzi

    Lecce

  • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori

    Meldola

  • Istituto Europeo di Oncologia

    Milan

  • Istituto Nazionale Tumori

    Milan

  • Ospedale San Paolo

    Milan

  • A.O. U.L.S.S. 13

    Mirano

  • A.O.U. Policlinico Modena

    Modena

  • Azienda Ospedaliera Cardarelli

    Naples, 80131

  • A.O.U. Seconda Università di Napoli

    Naples

  • AORN Ospedale dei Colli - Osp Monaldi

    Naples

  • Istituto Nazionale Tumori Fondazione G. Pascale

    Naples

  • Istituto Sacro Cuore Don Calabria

    Negrar

  • A.O.U. Maggiore della Carità

    Novara

  • Istituto Oncologico Veneto

    Padova

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

    Palermo, PA, 90146

  • Policlinico Giaccone

    Palermo

  • Fondazione Salvatore Maugeri

    Pavia

  • Osp. S. Maria della Misericordia

    Perugia

  • A.O. Ospedali Riuniti Marche Nord

    Pesaro

  • Ospedale Guglielmo da Saliceto

    Piacenza

  • A.O. San Carlo

    Potenza

  • Ospedale di Prato

    Prato, PO, 59100

  • Ospedale Santa Maria delle Croci - AUSL

    Ravenna

  • Ospedale Umberto I

    Ravenna

  • Ospedale degli Infermi Rimini - Ospedale Cervesi Cattolica

    Rimini

  • IRCCS Centro di Riferimento Oncologico Basilicata

    Rionero in Vulture

  • Istituto Regina Elena

    Roma

  • Ospedale Camillo Forlanini

    Roma

  • Ospedale S. Giovanni Calibita Fatebenefratelli

    Roma

  • Policlinico Universitario Campus Bio Medico

    Roma

  • Ospedale di Sondrio

    Sondrio

  • Ospedale Fabrizio Spaziani di Frosinone

    Sora

  • Ospedale S. Chiara

    Trento, TN, 38100

  • Ospedale Maggiore

    Trieste

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

    Udine

  • Ospedale S. Andrea

    Vercelli

  • A.O.U. Integrata

    Verona

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

    Vicenza, VI, 36100

  • ASL Viterbo - Ospedale Belcolle

    Viterbo

Other trials in Italy

About this study

Official title: 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.

Read the detailed description

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

Being tested
Erlotinib, Bevacizumab
Keywords
stage IV, stage IIIB, EGFR mutation, non-squamous, liquid biopsy, erlotinib, bevacizumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02633189
Study groupRoleWhat they receive
erlotinib and bevacizumabExperimentalNot described
Receives: Drug: Erlotinib; Drug: Bevacizumab
erlotinibActive comparatorNot described
Receives: Drug: Erlotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. progression free survival

    as determined by investigator

    Measured: up to 2 years

  2. progression free survival

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

    Measured: up to 2 years

Secondary outcomes (6)

  1. overall survival

    Measured: 1 year

  2. changes in quality of life scores from baseline

    Measured: up to 2 years

  3. number of patients with complete and partial responses , investigator assessed

    Measured: 6 months

  4. number of patients with complete and partial responses , centrally reviewed

    Measured: 6 months

  5. worst grade toxicity per patient

    Measured: up to one year

  6. progression free survival according to type of EGFR mutation (exon 19del, exon 21L858R, other)

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Dec 2015 (estimated)
  2. Study startApr 2016
  3. Primary completionDec 2023 (estimated)
  4. Study completionJul 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02633189
Sponsor's protocol ID
BEVERLY
Other IDs
2015-002235-17, 2015
Acronym
BEVERLY
Status last verified
Mar 2023
First submitted
15 Dec 2015
Last updated
24 Mar 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 35659580

  • 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.

    PubMed 33067126

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Erlotinib and Bevacizumab in people with Non-squamous Non-small Cell Lung Cancer, run by National Cancer Institute, Naples at 55 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 24 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 55 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

progression free survival (time frame: up to 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02633189, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2023.

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