BELIEF (Bevacizumab and ErLotinib In EGFR Mut+ NSCLC)
Condition: Lung Cancer
MeSH terms: Lung Neoplasms
Intervention: Erlotinib; Bevacizumab
Intervention description: Patients will be treated with erlotinib, 150 mg p.o., daily; Patients will be treated with bevacizumab 15 mg/kg i.v. on day 1 of each 3-week cycle (+/- 3 days)
Intervention MeSH terms: Bevacizumab; Erlotinib Hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 109.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: non small cell lung cancer; advanced; non-squamous; EGFR; mutations

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.
    

Eligibility 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