BELIEF (Bevacizumab and ErLotinib In EGFR Mut+ NSCLC)

ETOP IBCSG Partners Foundation

Status and phase: Completed; Phase 2

Conditions: Lung Cancer

Treatments: Drug: Bevacizumab; Drug: Erlotinib

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT01562028

MO27911 (Other Identifier)

ETOP 2-11 / MO27911

2011-004481-15 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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

Enrollment: 109 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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109 participants in 1 patient group

Erlotinib plus bevacizumab

Experimental group

Description:

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

Treatment:

Drug: Erlotinib

Drug: Bevacizumab