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

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ClinicalTrials.gov Identifier: NCT01562028
Recruitment Status : Completed
First Posted : March 23, 2012
Last Update Posted : March 21, 2019
Sponsor:
Collaborator:
Spanish Lung Cancer Group
Information provided by (Responsible Party):
European Thoracic Oncology Platform

Brief 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. 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 or disease Intervention/treatment Phase
Lung Cancer Drug: Erlotinib Drug: Bevacizumab Phase 2

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


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 110 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : June 2012
Actual Primary Completion Date : October 31, 2018
Actual Study Completion Date : October 31, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
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)




Primary Outcome Measures :
  1. 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 :
  1. 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).

  2. 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.

  3. Adverse events [ 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.

  4. 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.

  5. 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.

  6. 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.



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

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01562028


  Hide Study Locations
Locations
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France
Centre Francois Baclesse
Caen, France, 14000
Hôpital de Marseille
Marseille, France, 13915
Germany
Hospital Grosshansdorf
Grosshansdorf, Germany, 22927
Thoraxklinik Heidelberg GmbH
Heidelberg, Germany, 69126
Lungenklinik Hemer
Hemer, Germany, 58675
Universitätsklinikum Ulm
Ulm, Germany, 89081
Greece
University General Hospital of Heraklion
Heraklion, Greece
Papageorgias Hospital
Thessaloniki, Greece
Ireland
St Vincent's University Hospital
Dublin, Ireland
St. James's Hospital
Dublin, Ireland
University Hospital Galway
Galway, Ireland
Mid-Western Regional Hospital
Limerick, Ireland
AMCCH
Tallaght, Ireland
Italy
Ospedale San Gerardo
Monza, Italy, 20900
Istituto Oncologico Veneto IRCCS
Padova, Italy, 35128
Casa di Cura Maddalena
Palermo, Italy, 90146
Policlinico Tor Vergata Roma
Roma, Italy, 00133
San Camillo Hospital
Roma, Italy, 00151
Policlinico Umberto
Roma, Italy, 00161
Spain
Hospital General Universitario Alicante
Alicante, Spain, 03010
ICO - Hospital Universitari Germans Trias i Pujol
Badalona, Spain, 08916
Hospital De La Santa Creu I Sant Pau
Barcelona, Spain, 08025
Vall d'Hebron University Hospital
Barcelona, Spain, 08035
Hospital Clínic Barcelona
Barcelona, Spain, 08036
ICO - Girona
Girona, Spain, 17007
ICO - Hospital Duran i Reynals
L'Hospitalet de Llobregat, Spain, 08907
Hospital Clinico Universitario San Carlos
Madrid, Spain, 28040
Hospital 12 de Octubre
Madrid, Spain, 28041
Hospital General de Valencia
Valencia, Spain, 46014
Hospital La Fe
Valencia, Spain, 46026
Switzerland
University Hospital Basel
Basel, Switzerland, 4031
Istituto Oncologica della Svizzera Italiana
Bellinzona, Switzerland, 6650
Inselspital Bern
Bern, Switzerland, 3010
Geneva University Hospital
Geneva, Switzerland, 1211
Fondation du centre Pluridisciplinaire d'Oncologie (CePO)
Lausanne, Switzerland, 1011
Kantonsspital Luzern
Luzern, Switzerland, 6016
Kantonsspital St. Gallen
St. Gallen, Switzerland, 9007
Onkologiezentrum Berner Oberland
Thun, Switzerland, 3600
Kantonsspital Winterthur
Winterthur, Switzerland, 8401
University Hospital Zurich
Zurich, Switzerland, 8091
United Kingdom
Mid Essex Hospital Services NHS Trust
Chelmsford, Essex, United Kingdom, CM1 7ET
Queen's Hospital
Burton-upon-Trent, United Kingdom, DE13 0RB
University Hospitals of Leicester
Leicester, United Kingdom, LE1 5WW
Royal Marsden Hospital
London, United Kingdom, SW3 6JJ
Kent Oncology Centre
Maidstone, United Kingdom, ME16 9QQ
Christie Hospital Manchester
Manchester, United Kingdom, M20 4BX
Wythenshawe Hospital Manchester
Manchester, United Kingdom, M23 9LT
Wrexham Maelor Hospital
Wrexham, United Kingdom, LL13 7TD
Sponsors and Collaborators
European Thoracic Oncology Platform
Spanish Lung Cancer Group
Investigators
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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

Publications:
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).

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: European Thoracic Oncology Platform
ClinicalTrials.gov Identifier: NCT01562028     History of Changes
Other Study ID Numbers: ETOP 2-11 / MO27911
2011-004481-15 ( EudraCT Number )
MO27911 ( Other Identifier: Roche )
First Posted: March 23, 2012    Key Record Dates
Last Update Posted: March 21, 2019
Last Verified: March 2019

Keywords provided by European Thoracic Oncology Platform:
non small cell lung cancer
advanced
non-squamous
EGFR
mutations

Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Bevacizumab
Erlotinib Hydrochloride
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action