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BELIEF (Bevacizumab and ErLotinib In EGFR Mut+ NSCLC) (BELIEF)

This study is ongoing, but not recruiting participants.
Spanish Lung Cancer Group
Information provided by (Responsible Party):
European Thoracic Oncology Platform Identifier:
First received: March 22, 2012
Last updated: November 11, 2016
Last verified: November 2016


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.

Condition Intervention Phase
Lung Cancer
Drug: Erlotinib
Drug: Bevacizumab
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by European Thoracic Oncology Platform:

Primary Outcome Measures:
  • Progression free survival [ Time Frame: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient ]
    Time from the date of enrolment until documented progression or death, whichever occurs first.

Secondary Outcome Measures:
  • Time to treatment failure [ Time Frame: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient ]
    Time from the date of enrolment to discontinuation of treatment for any reason (including progression of disease, treatment toxicity, refusal and death).

  • Objective response [ Time Frame: termination of trial treatment ]
    Best overall response (complete remission or partial remission) across all assessment time-points according to RECIST Criteria 1.1, during the period from enrolment to termination of trial treatment.

  • Toxicity [ Time Frame: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient ]
    Adverse events graded according to NCI CTCAE V4.

  • Disease control [ Time Frame: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient ]
    Achievement of objective response or stable disease for at least 6 weeks.

  • Duration of response [ Time Frame: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient ]
    Interval from the date of first documentation of objective response by RECIST to the date of first documented progression or relapse.

  • Overall survival (OS) [ Time Frame: Within 6 months of the last visit of last patient, approximately 54 months after inclusion of first patient ]
    Time from the date of enrolment until death from any cause.

Enrollment: 110
Study Start Date: June 2012
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erlotinib plus bevacizumab
Patients 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
Drug: Erlotinib
Patients will be treated with erlotinib, 150 mg p.o., daily
Other Name: Tarceva (R) (Roche)
Drug: Bevacizumab
Patients will be treated with bevacizumab 15 mg/kg i.v. on day 1 of each 3-week cycle (+/- 3 days)
Other Name: Avastin (R) Roche)

Detailed Description:


  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


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


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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.
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01562028

  Show 48 Study Locations
Sponsors and Collaborators
European Thoracic Oncology Platform
Spanish Lung Cancer Group
Study Chair: Rafael Rosell, MD Catalan Institute of Oncology, Hospital Germans Trias i Pujol
Study Chair: Stahel Rolf, MD Laboratory of Molecular Oncology, Clinic of Oncology, University Hospital Zuerich
Study Chair: Miquel Taron Medical Oncology Service-ICO, Hospital Germans Trias i Pujol
  More Information

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, Muñoz-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 Français de Pneumo-Cancérologie 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.
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).

Responsible Party: European Thoracic Oncology Platform Identifier: NCT01562028     History of Changes
Other Study ID Numbers: ETOP 2-11 / MO27911
2011-004481-15 ( EudraCT Number )
MO27911 ( Other Identifier: Roche )
Study First Received: March 22, 2012
Last Updated: November 11, 2016

Keywords provided by European Thoracic Oncology Platform:
non small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Erlotinib Hydrochloride
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on April 26, 2017