BELIEF (Bevacizumab and ErLotinib In EGFR Mut+ NSCLC)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by European Thoracic Oncology Platform
Sponsor:
Collaborator:
Spanish Lung Cancer Group
Information provided by (Responsible Party):
European Thoracic Oncology Platform
ClinicalTrials.gov Identifier:
NCT01562028
First received: March 22, 2012
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Time from the date of enrolment until death from any cause.


Estimated Enrollment: 102
Study Start Date: June 2012
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: June 2016 (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:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  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 ClinicalTrials.gov identifier: NCT01562028

Contacts
Contact: Barbara Ruepp, PhD +41313899391 belief@etop-eu.org

  Show 48 Study Locations
Sponsors and Collaborators
European Thoracic Oncology Platform
Spanish Lung Cancer Group
Investigators
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

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).

Responsible Party: European Thoracic Oncology Platform
ClinicalTrials.gov Identifier: NCT01562028     History of Changes
Other Study ID Numbers: ETOP 2-11 / MO27911, 2011-004481-15, MO27911
Study First Received: March 22, 2012
Last Updated: August 18, 2014
Health Authority: Switzerland: Swissmedic
Spain: Agencia Española de Medicamentos y Productos Sanitarios
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Ireland: Irish Medicines Board
Greece: Ministry of Health and Welfare

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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Bevacizumab
Erlotinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014