BELIEF (Bevacizumab and ErLotinib In EGFR Mut+ NSCLC)

NCT01562028 | Completed Phase 2 Results DMC

• 3 other identifiers: ETOP 2-11 / MO279112011-004481-15MO27911
• Study Type: interventional
• Target: 109
• Locations: 8 countries
• Sites: 48

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.

Conditions

Lung Cancer

Keywords

non small cell lung cancer; advanced; non-squamous; EGFR; mutations

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (6)

• Overall Survival

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

• Time to Treatment Failure

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

• Objective Response

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

• Disease Control

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

• Duration of Response

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

Study Arms (1)

Erlotinib plus bevacizumab

EXPERIMENTAL

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; Drug: Bevacizumab

Interventions

Erlotinib DRUG

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

Also known as: Tarceva (R) (Roche)

Erlotinib plus bevacizumab

Bevacizumab DRUG

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

Also known as: Avastin (R) Roche)

Erlotinib plus bevacizumab

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Spanish Lung Cancer Group: collaborator

Study Sites (48)

Centre Francois Baclesse

Caen, 14000, France

Location

Hôpital de Marseille

Marseille, 13915, France

Location

Hospital Grosshansdorf

Großhansdorf, 22927, Germany

Location

Thoraxklinik Heidelberg GmbH

Heidelberg, 69126, Germany

Location

Lungenklinik Hemer

Hemer, 58675, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

University General Hospital of Heraklion

Heraklion, Greece

Location

Papageorgias Hospital

Thessaloniki, Greece

Location

St Vincent's University Hospital

Dublin, Ireland

Location

St. James's Hospital

Dublin, Ireland

Location

University Hospital Galway

Galway, Ireland

Location

Mid-Western Regional Hospital

Limerick, Ireland

Location

AMCCH

Tallaght, Ireland

Location

Ospedale San Gerardo

Monza, 20900, Italy

Location

Istituto Oncologico Veneto IRCCS

Padua, 35128, Italy

Location

Casa di Cura Maddalena

Palermo, 90146, Italy

Location

Policlinico Tor Vergata Roma

Roma, 00133, Italy

Location

San Camillo Hospital

Roma, 00151, Italy

Location

Policlinico Umberto

Roma, 00161, Italy

Location

Hospital General Universitario Alicante

Alicante, 03010, Spain

Location

ICO - Hospital Universitari Germans Trias i Pujol

Badalona, 08916, Spain

Location

Hospital De La Santa Creu I Sant Pau

Barcelona, 08025, Spain

Location

Vall d'Hebron University Hospital

Barcelona, 08035, Spain

Location

Hospital Clínic Barcelona

Barcelona, 08036, Spain

Location

ICO - Girona

Girona, 17007, Spain

Location

ICO - Hospital Duran i Reynals

L'Hospitalet de Llobregat, 08907, Spain

Location

Hospital Clinico Universitario San Carlos

Madrid, 28040, Spain

Location

Hospital 12 de Octubre

Madrid, 28041, Spain

Location

Hospital General de Valencia

Valencia, 46014, Spain

Location

Hospital La Fe

Valencia, 46026, Spain

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

Istituto Oncologica della Svizzera Italiana

Bellinzona, 6650, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Geneva University Hospital

Geneva, 1211, Switzerland

Location

Fondation du centre Pluridisciplinaire d'Oncologie (CePO)

Lausanne, 1011, Switzerland

Location

Kantonsspital Luzern

Lucerne, 6016, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

Onkologiezentrum Berner Oberland

Thun, 3600, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

Location

University Hospital Zurich

Zurich, 8091, Switzerland

Location

Mid Essex Hospital Services NHS Trust

Chelmsford, Essex, CM1 7ET, United Kingdom

Location

Queen's Hospital

Burton-on-Trent, DE13 0RB, United Kingdom

Location

University Hospitals of Leicester

Leicester, LE1 5WW, United Kingdom

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

Kent Oncology Centre

Maidstone, ME16 9QQ, United Kingdom

Location

Christie Hospital Manchester

Manchester, M20 4BX, United Kingdom

Location

Wythenshawe Hospital Manchester

Manchester, M23 9LT, United Kingdom

Location

Wrexham Maelor Hospital

Wrexham, LL13 7TD, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 15118125 BACKGROUND

• 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.

  PMID: 22285168 BACKGROUND

• 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.

  PMID: 15728811 BACKGROUND

• 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).

  BACKGROUND

• 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.

  PMID: 28408243 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Erlotinib Hydrochloride; Bevacizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

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

Results Point of Contact

• Title: Heidi Roschitzki-Voser
• Organization: European Thoracic Oncology Platform (ETOP)

belief@etop-eu.org

+41 31 511 94 18

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2012
• First Posted: March 23, 2012
• Study Start: June 1, 2012
• Primary Completion: October 31, 2018
• Study Completion: October 31, 2018
• Last Updated: August 24, 2022
• Results First Posted: October 31, 2019

Record last verified: 2022-08

Locations

GB (8); IE (5); DE (4); GR (2); FR (2); CH (10); IT (6); ES (11)