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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 : November 5, 2018
Sponsor:
Collaborator:
Spanish Lung Cancer Group
Information provided by (Responsible Party):
European Thoracic Oncology Platform

Tracking Information
First Submitted Date  ICMJE March 22, 2012
First Posted Date  ICMJE March 23, 2012
Last Update Posted Date November 5, 2018
Study Start Date  ICMJE June 2012
Actual Primary Completion Date October 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 22, 2012)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01562028 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 22, 2012)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE BELIEF (Bevacizumab and ErLotinib In EGFR Mut+ NSCLC)
Official Title  ICMJE An Open-label Phase II Trial of Erlotinib and Bevacizumab in Patients With Advanced Non-small Cell Lung Cancer and Activating EGFR Mutations
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.

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

Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lung Cancer
Intervention  ICMJE
  • 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)
Study Arms 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
Interventions:
  • Drug: Erlotinib
  • Drug: Bevacizumab
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 9, 2015)
110
Original Estimated Enrollment  ICMJE
 (submitted: March 22, 2012)
102
Actual Study Completion Date October 31, 2018
Actual Primary Completion Date October 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Germany,   Greece,   Ireland,   Italy,   Spain,   Switzerland,   United Kingdom
Removed Location Countries Netherlands
 
Administrative Information
NCT Number  ICMJE NCT01562028
Other Study ID Numbers  ICMJE ETOP 2-11 / MO27911
2011-004481-15 ( EudraCT Number )
MO27911 ( Other Identifier: Roche )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party European Thoracic Oncology Platform
Study Sponsor  ICMJE European Thoracic Oncology Platform
Collaborators  ICMJE Spanish Lung Cancer Group
Investigators  ICMJE
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
PRS Account European Thoracic Oncology Platform
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP