BEVERLY: A randomized open-label phase 3 trial comparing bevacizumab + erlotinib vs erlotinib alone as first line treatment of patients with EGFR mutated advanced non squamous non small cell lung cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

23 Nov 2015 → ongoing

Decision date (initial)

2024-11-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516843-15-00

EudraCT number

2015-002235-17

ClinicalTrials.gov

NCT02633189

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The purpose of this study is to test whether the combination of bevacizumab and
erlotinib can prolong progression free survival as compared with erlotinib alone as
first-line treatment in patients with non small cell lung cancer (NSCLC) with activating
mutation of EGFR.

Secondary objectives 1

1. Detailed Description: The coprimary objectives are to assess investigator-assess, and blinded independent centrally-reviewed progression-free survival .

Conditions and MedDRA coding

Non-squamous Non-small Cell Lung Cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Age ≥18 years • Histologic documentation of primary non squamous non-small cell lung carcinoma • Stage IV or IIIB disease with supraclavear metastatic nodes (according to TNM 7th edition) • Activating epidermal growth factor receptor mutation (exon19 deletion or exon 21 L858R mutation or other activating/sensitizing mutations, such as exon 21 L861Q, exon 18 G719S, G719A and G719C, exon 20 S768I and V769L). EGFR mutation testing must be performed at participating centres in a certified lab (AIOM-SIAPEC program or other European Quality Assurance [EQA] schemes) • Clinical or radiologic evidence of disease (at least one target or non target lesion according to RECIST 1.1) • ECOG performance status 0 to 2 • Life expectancy > 3 months • Use of an acceptable mean of contraception for men and women of childbearing potential • Written informed consent

Exclusion criteria 1

1. • EGFR T790M mutation alone or exon 20 insertions as unique mutation • Tumors with a squamous component • Prior chemotherapy or any other medical treatment for advanced NSCLC (previous neoadjuvant or adjuvant chemotherapy is allowed if > 6 months previously) • Radiotherapy to any site for any reason within 28 days prior to randomization (palliative radiotherapy to bone lesions is allowed if ≥ 14 days before randomization) • Pregnancy or nursing • Concomitant pathologies or laboratory alterations or concomitant medications use that prevent or contraindicate the use of erlotinib or bevacizumab

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To test whether the combination of bevacizumab and erlotinib can prolong investigator assessed (IA-PFS) and blinded independent centrally-reviewed progression-free survival (BICR-PFS) as compared with erlotinib alone as first-line treatment in patients with NSCLC with activating mutation of EGFR. Note: CT (or other pertinent) scans performed at baseline and during follow-up will be collected and reviewed by an independent central panel of radiologists who will be blinded to the assigned tr

Secondary endpoints 1

1. • To compare the two arms in terms of o overall survival o quality of life (EORTC C30 + LC13) o centrally reviewed objective response rate (RECIST v.1.1) o investigator assessed objective response rate (RECIST v.1.1) o adverse events (CTCAE 4.03 version) • To test whether an interaction exists between treatment arms and type of EGFR mutation (exon 19del vs exon 21 L858R vs other) • To explore other possible predictive factors and their interaction with treatment arms • To explore pro

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Sponsor organisation

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Address

Via Mariano Semmola 52

City

Naples

Postcode

80131

Country

Italy

Scientific contact point

Organisation

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Contact name

Piccirillo

Public contact point

Organisation

IRCCS Istituto Nazionale Tumori Fondazione Pascale

Contact name

Piccirillo

Locations

1 EU/EEA country · 16 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications