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Lung CancerPhase 2BELIEFNCT01562028

BELIEF (Bevacizumab and ErLotinib In EGFR Mut+ NSCLC)

A Phase 2 study testing Erlotinib and Bevacizumab in people with Lung Cancer, run by ETOP IBCSG Partners Foundation at 48 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Rationale: Advanced non-small-cell lung cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) mutations (del19 or L858R) show an impressive progression-free survival between 9 and 14 months when treated with erlotinib. However, the presence of EGFR mutations can only imperfectly predict outcome. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Cancer
What is being tested?
Erlotinib and Bevacizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
109 participants
Where
48 sitesin 8 countries
Study dates
Jun 2012to 31 Oct 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years
  • ECOG performance status 0-2
  • Adequate haematological function, coagulation, liver function and renal function
  • Pathological diagnosis of predominantly non-squamous, non-small-cell lung cancer (NSCLC)
  • TNM version 7 stage IV disease including M1a (malignant effusion) or M1b (distant metastasis), or locally advanced disease not amenable to curative treatment (including patients progressing after radiochemotherapy for stage III disease)
  • Measurable or evaluable disease (according to RECIST 1.1 criteria).
  • Centrally confirmed EGFR exon 19 deletion (del19) or exon 21 mutation (L858R)

Who cannot join

  • Patients with increased risk of bleeding
  • Patients with clinically significant cardiovascular diseases
  • Patients with a history of thrombosis or thromboembolism in the 6 months prior to treatment
  • Patients with gastrointestinal problems
  • Patients with neurologic problems
  • Patients who have had in the past 5 years any previous or concomitant malignancy EXCEPT adequately treated basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix or bladder, in situ breast carcinoma.
Show all 10Show fewer
  • Patients with any known significant ophthalmologic anomaly of the ocular surface
  • Patients who received prior chemotherapy for metastatic disease
  • Patients who received previous treatment for lung cancer with drugs targeting EGFR or VEGF
  • Pregnancy

Trial locations and contacts

48 sites in 8 countries.

48 sites in 8 countries

Spain11 sites

  • Hospital General Universitario Alicante

    Alicante, 03010

  • ICO - Hospital Universitari Germans Trias i Pujol

    Badalona, 08916

  • Hospital De La Santa Creu I Sant Pau

    Barcelona, 08025

  • Vall d'Hebron University Hospital

    Barcelona, 08035

  • Hospital Clínic Barcelona

    Barcelona, 08036

  • ICO - Girona

    Girona, 17007

  • ICO - Hospital Duran i Reynals

    L'Hospitalet de Llobregat, 08907

  • Hospital Clinico Universitario San Carlos

    Madrid, 28040

  • Hospital 12 de Octubre

    Madrid, 28041

  • Hospital General de Valencia

    Valencia, 46014

  • Hospital La Fe

    Valencia, 46026

Other trials in Spain

Switzerland10 sites

  • University Hospital Basel

    Basel, 4031

  • Istituto Oncologica della Svizzera Italiana

    Bellinzona, 6650

  • Inselspital Bern

    Bern, 3010

  • Geneva University Hospital

    Geneva, 1211

  • Fondation du centre Pluridisciplinaire d'Oncologie (CePO)

    Lausanne, 1011

  • Kantonsspital Luzern

    Lucerne, 6016

  • Kantonsspital St. Gallen

    Sankt Gallen, 9007

  • Onkologiezentrum Berner Oberland

    Thun, 3600

  • Kantonsspital Winterthur

    Winterthur, 8401

  • University Hospital Zurich

    Zurich, 8091

Other trials in Switzerland

United Kingdom8 sites

  • Queen's Hospital

    Burton-on-Trent, DE13 0RB

  • Mid Essex Hospital Services NHS Trust

    Chelmsford, Essex, CM1 7ET

  • University Hospitals of Leicester

    Leicester, LE1 5WW

  • Royal Marsden Hospital

    London, SW3 6JJ

  • Kent Oncology Centre

    Maidstone, ME16 9QQ

  • Christie Hospital Manchester

    Manchester, M20 4BX

  • Wythenshawe Hospital Manchester

    Manchester, M23 9LT

  • Wrexham Maelor Hospital

    Wrexham, LL13 7TD

Other trials in United Kingdom

Italy6 sites

  • Ospedale San Gerardo

    Monza, 20900

  • Istituto Oncologico Veneto IRCCS

    Padova, 35128

  • Casa di Cura Maddalena

    Palermo, 90146

  • Policlinico Tor Vergata Roma

    Roma, 00133

  • San Camillo Hospital

    Roma, 00151

  • Policlinico Umberto

    Roma, 00161

Other trials in Italy

Ireland5 sites

  • St Vincent's University Hospital

    Dublin

  • St. James's Hospital

    Dublin

  • University Hospital Galway

    Galway

  • Mid-Western Regional Hospital

    Limerick

  • AMCCH

    Tallaght

Other trials in Ireland

Germany4 sites

  • Hospital Grosshansdorf

    Großhansdorf, 22927

  • Thoraxklinik Heidelberg GmbH

    Heidelberg, 69126

  • Lungenklinik Hemer

    Hemer, 58675

  • Universitätsklinikum Ulm

    Ulm, 89081

Other trials in Germany

France2 sites

  • Centre Francois Baclesse

    Caen, 14000

  • Hôpital de Marseille

    Marseille, 13915

Other trials in France

Greece2 sites

  • University General Hospital of Heraklion

    Heraklion

  • Papageorgias Hospital

    Thessaloniki

Other trials in Greece

About this study

Official title: An Open-label Phase II Trial of Erlotinib and Bevacizumab in Patients With Advanced Non-small Cell Lung Cancer and Activating EGFR Mutations

Rationale:

Advanced non-small-cell lung cancer (NSCLC) patients harbouring epidermal growth factor receptor (EGFR) mutations (del19 or L858R) show an impressive progression-free survival between 9 and 14 months when treated with erlotinib. However, the presence of EGFR mutations can only imperfectly predict outcome. The investigators hypothesize that progression-free survival could be influenced both by the pretreatment EGFR T790M mutation and by components of DNA repair pathways.

The investigators propose a model of treatment whereby patients with EGFR mutations (single or with T790M) can attain a benefit with longer overall PFS when treated with erlotinib plus bevacizumab. When the patients are grouped by BRCA1 mRNA levels and T790M the hypothesis is that the combination of erlotinib plus bevacizumab can improve the PFS in all subgroups.

Read the detailed description

Objectives:

  1. To determine long-term outcome of patients with advanced non-squamous NSCLC harbouring EGFR mutations with or without T790M mutation at diagnosis and treated with the combination of erlotinib and bevacizumab. Primary endpoint: progression-free survival
  2. To evaluate the efficacy and tolerability of the combination
  3. To evaluate the correlation of BRCA1 mRNA and AEG-1 mRNA expression and T790M with progression-free survival
  4. To monitor EGFR mutations (including T790M) in serum and plasma longitudinally
  5. To evaluate molecular biomarkers related to EGFR TKI and bevacizumab

Design:

This is a multinational, multi-center phase II trial of erlotinib plus bevacizumab in patients with advanced non-squamous NSCLC harbouring EGFR mutations confirmed by central re-assessment. Patients will be stratified into two subgroups, with and without EGFR T790M mutation. The stratification will be done after the inclusion of patients.

Sample size: 102 patients

Conditions
Lung Cancer
Being tested
Erlotinib, Bevacizumab
Keywords
non small cell lung cancer, advanced, non-squamous, EGFR, mutations
Medical subject headings
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • ErlotinibDrug

    Also called Tarceva (R) (Roche)

    Patients will be treated with erlotinib, 150 mg p.o., daily

  • BevacizumabDrug

    Also called Avastin (R) Roche)

    Patients will be treated with bevacizumab 15 mg/kg i.v. on day 1 of each 3-week cycle (+/- 3 days)

Study groups in NCT01562028
Study groupRoleWhat they receive
Erlotinib plus bevacizumabExperimentalPatients will be treated with erlotinib and bevacizumab. Bevacizumab: 15 mg/kg i.v. on day 1 of each 3-week cycle (+/- 3 days) Erlotinib: 150 mg p.o., daily
Receives: Drug: Erlotinib; Drug: Bevacizumab

What is being measured

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

  1. Progression Free Survival

    Time from the date of enrollment until an investigator-documented progression or death, whichever occurs first.

    Assessment of Progressive Disease (PD) is based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1): at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: From the date of enrollment until documented progression or death, whichever occurs first, assessed up to 48 months.

Secondary outcomes (6)

  1. Overall Survival

    Time from the date of enrollment until death from any cause.

    Measured: From the date of enrollment until death, assessed up to 48 months.

  2. Time to Treatment Failure

    Time from the date of enrollment to discontinuation of treatment for any reason including progression of disease (based on RECIST v1.1), treatment toxicity (adverse events classified according to NCI CTCAE version 4.), refusal and death.

    Measured: From the date of enrollment until discontinuation of treatment, assessed up to 48 months.

  3. Objective Response

    Objective response is defined as best overall response (CR or PR) across all assessment time-points during the period from enrollment to termination of trial treatment. Objective response, along with progressive and stable disease, will be determined using RECIST 1.1 criteria:

    Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters.

    Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on the trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters recorded on the trial.

    Measured: Assessed across all time-points from enrollment to termination of trial treatment (max 48 months).

  4. Disease Control

    Disease control is defined as achieving objective response (CR or PR, across all time-points from enrollment to termination of trial treatment) or stable disease for at least 6 weeks. Objective response, along with SD (disease control) and PD (no disease control), will be determined using RECIST 1.1 criteria:

    Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters.Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on the trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters recorded on the trial.

    Measured: Assessed across all time-points from enrollment to termination of trial treatment (max 48 months).

  5. Duration of Response

    Interval from the date of first documentation of objective response (CR or PR) to the date of first documented progression or relapse. Assessment of Objective response and Progressive Disease (PD) is based on the RECIST 1.1 criteria:

    Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters.

    Progression (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum recorded on the trial. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters recorded on the trial.

    Measured: Assessed across all time-points from enrollment to to the date of first documented progression or relapse (max 48 months).

  6. Adverse Events

    Adverse events graded according to NCI CTCAE V4.

    Measured: Assessed across all time-points until end of treatment (30 +/-5 days following the last dose of study drug) (max 48 months).

Timeline

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

  1. First posted23 Mar 2012 (estimated)
  2. Study startJun 2012
  3. Primary completion31 Oct 2018
  4. Study completion31 Oct 2018

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
109 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01562028
Sponsor's protocol ID
ETOP 2-11 / MO27911
Other IDs
2011-004481-15, MO27911
Acronym
BELIEF
Status last verified
Aug 2022
First submitted
22 Mar 2012
Last updated
26 Aug 2026
Data monitoring committee
Yes

Publications

  • Paez JG, Janne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, Naoki K, Sasaki H, Fujii Y, Eck MJ, Sellers WR, Johnson BE, Meyerson M. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science. 2004 Jun 4;304(5676):1497-500. doi: 10.1126/science.1099314. Epub 2004 Apr 29.

    PubMed 15118125

  • Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group in collaboration with Groupe Francais de Pneumo-Cancerologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. doi: 10.1016/S1470-2045(11)70393-X. Epub 2012 Jan 26.

    PubMed 22285168

  • Kobayashi S, Boggon TJ, Dayaram T, Janne PA, Kocher O, Meyerson M, Johnson BE, Eck MJ, Tenen DG, Halmos B. EGFR mutation and resistance of non-small-cell lung cancer to gefitinib. N Engl J Med. 2005 Feb 24;352(8):786-92. doi: 10.1056/NEJMoa044238.

    PubMed 15728811

  • Kabbinavar F, Miller VA, Johnson BE, O'Connor P, Soh C-H, ATLAS Investigators. Overall survival in ATLAS, a Phase IIIb trial comparing bevacizumab therapy +/- erlotinib after completion of chemotherapy with bevacizumab for first-line treatment of locally advanced, recurrent, or metastatic non-small cell lung cancer (NSCLC). J Clin Oncol 2010; 28 (May suppl; abstr 7526).

  • Rosell R, Dafni U, Felip E, Curioni-Fontecedro A, Gautschi O, Peters S, Massuti B, Palmero R, Aix SP, Carcereny E, Fruh M, Pless M, Popat S, Kotsakis A, Cuffe S, Bidoli P, Favaretto A, Froesch P, Reguart N, Puente J, Coate L, Barlesi F, Rauch D, Thomas M, Camps C, Gomez-Codina J, Majem M, Porta R, Shah R, Hanrahan E, Kammler R, Ruepp B, Rabaglio M, Kassapian M, Karachaliou N, Tam R, Shames DS, Molina-Vila MA, Stahel RA; BELIEF collaborative group. Erlotinib and bevacizumab in patients with advanced non-small-cell lung cancer and activating EGFR mutations (BELIEF): an international, multicentre, single-arm, phase 2 trial. Lancet Respir Med. 2017 May;5(5):435-444. doi: 10.1016/S2213-2600(17)30129-7. Epub 2017 Apr 10.

    PubMed 28408243

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Erlotinib and Bevacizumab in people with Lung Cancer, run by ETOP IBCSG Partners Foundation at 48 sites in 8 countries.

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 7 inclusion and 10 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: finished, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in Spain, Switzerland, United Kingdom, Italy, Ireland and 3 more countries. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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: From the date of enrollment until documented progression or death, whichever occurs first, assessed up to 48 months.). 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 NCT01562028, which also lists 5 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 26 Aug 2026.

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