Study Comparing Bevacizumab + Erlotinib vs Erlotinib Alone as First Line Treatment of Patients With EGFR Mutated Advanced Non Squamous Non Small Cell Lung Cancer

Non-squamous Non-small Cell Lung Cancer Clinical Trial

— BEVERLY  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02633189
• Other study ID #: BEVERLY
• Secondary ID: 2015-002235-17
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: April 2016
• Est. completion date: July 2024

Study information

• Verified date: March 2023
• Source: National Cancer Institute, Naples
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

The co-primary objectives are to assess investigator-assess, and blinded independent centrally-reviewed progression-free survival .

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. completion date: July 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Age =18 years

2. Histological documentation of primary non squamous lung carcinoma

3. Stage IV or IIIB disease with supraclavicular metastatic nodes (according to TNM 7th edition)

4. 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)

5. Clinical or radiologic evidence of disease (at least one target or non target lesion according to RECIST 1.1)

6. ECOG performance status 0 to 2

7. Life expectancy > 3 months

8. Use of an acceptable mean of contraception for men and women of childbearing potential

9. Written informed consent.

Exclusion Criteria:

1. EGFR T790M mutation alone or exon 20 insertions as unique mutation

2. Tumors with a squamous component

3. Prior chemotherapy or any other medical treatment for advanced NSCLC (previous neoadjuvant or adjuvant chemotherapy is allowed if > 6 months before randomisation)

4. 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)

5. Full-dose anticoagulation with warfarin

6. Current or recent (within 10 days of enrolment) use of aspirin (>325 mg/day) or chronic use of other full-dose nonsteroidal anti-inflammatory drugs (NSAIDs) with anti-platelet activity

7. Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4) are prohibited =< 7 days prior to registration

8. Receiving any medications or substances that are inducers of CYP3A4 use of inducers are prohibited =< 7 days prior to registration

9. Inadequate coagulation parameters:

• activated partial thromboplastin time (APTT) >1.5 x the upper limit of normal (ULN) or

• INR >1.5

10. Inadequate liver function, defined as:

• serum (total) bilirubin >1.5 x ULN

• AST/SGOT or ALT/SGPT >2.5 x ULN

11. Inadequate renal function, defined as:

• serum creatinine >2.0 mg/dl or >177 micromol/l

• urine dipstick for proteinuria >2+. Patients with > o = 1+ proteinuria at baseline dipstick analysis must undergo a 24-hour urine collection and must demonstrate =1g of protein in their 24-hour urine collection.

12. Pregnancy or breast-feeding

13. Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure >100 mmHg on antihypertensive medications)

14. History of gross hemoptysis within 3 months prior to randomization unless definitively treated with surgery or radiation

15. History of any of the following within 6 months prior to randomisation: serious systemic disease, unstable angina, New York Heart Association (NYHA) Grade 2 or greater Congestive Heart Failure (CHF), unstable symptomatic arrhythmia requiring medication, clinically significant peripheral vascular disease, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess

16. Serious, non-healing wound, ulcer, or bone fracture

17. Evidence of bleeding diathesis or coagulopathy or other serious or acute internal bleeding within 6 months prior to randomization

18. Central Nervous System (CNS) bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months

19. In-patient surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization

20. Minor surgical procedure, fine needle aspirations or core biopsy within 7 days prior to randomization

21. Anticipation of need for a major surgical procedure during the course of the study

22. Inability to take oral medication or requirement for intravenous (IV) alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption

23. Evidence of confusion or disorientation, or history of major psychiatric illness that may impair the patient's understanding of the Informed Consent Form or his/her ability to comply with study requirements

24. Any other invasive malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA)

25. Brain metastasis

26. Patients who have had radiotherapy = 4 weeks prior to the first dose of study treatment, but who are still experiencing acute toxic effects of radiotherapy

27. Known HIV positive patients (patients with both acute or chronic infection are excluded)

28. Active HBV or HCV infection (patients with chronic non-active infection are eligible)

29. Any already known inflammatory changes of the surface of the eye at baseline

30. Any other concomitant pathologies or laboratory alterations that prevent or contraindicate the use of erlotinib or bevacizumab.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-squamous Non-small Cell Lung Cancer

Intervention

Drug:
• Erlotinib
given orally 150 mg daily
• Bevacizumab
15 mg/kg intravenously every 21 days.

Locations

Country	Name	City	State
Italy	A.S.O. SS Antonio e Biagio e Cesare Arrigo	Alessandria
Italy	A.O. S. Giuseppe Moscati	Avellino
Italy	Centro Riferimento Oncologico	Aviano
Italy	AO G. Rummo	Benevento
Italy	Ospedale Senatore Antonio Perrino	Brindisi
Italy	Ospedale A. cardarelli	Campobasso
Italy	U.L.S.S. 15 Veneto	Camposampiero
Italy	Ospedale Ramazzini, Day Hospital Oncologico	Carpi	MO
Italy	A.O. Garibaldi Nesima	Catania
Italy	Centro Clinico Diagnostico G.B. Morgagni	Catania
Italy	Policlinico vittorio Emanuele	Catania
Italy	Ospedale Civile per gli Infermi	Faenza
Italy	Ospedale S. Croce	Fano
Italy	A.O.U. Arcispedale Sant'Anna	Ferrara
Italy	Ospedale Villa Scassi	Genova
Italy	Ospedale di Guastalla	Guastalla
Italy	A.O. Vito Fazzi	Lecce
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola
Italy	Istituto Europeo di Oncologia	Milano
Italy	Istituto Nazionale Tumori	Milano
Italy	Ospedale San Paolo	Milano
Italy	A.O. U.L.S.S. 13	Mirano
Italy	A.O.U. Policlinico Modena	Modena
Italy	A.O.U. Seconda Università di Napoli	Napoli
Italy	AORN Ospedale dei Colli - Osp Monaldi	Napoli
Italy	Azienda Ospedaliera Cardarelli	Napoli
Italy	Istituto Nazionale Tumori Fondazione G. Pascale	Napoli
Italy	Istituto Sacro Cuore Don Calabria	Negrar
Italy	A.O.U. Maggiore della Carità	Novara
Italy	Istituto Oncologico Veneto	Padova
Italy	Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico	Palermo	PA
Italy	Policlinico Giaccone	Palermo
Italy	Fondazione Salvatore Maugeri	Pavia
Italy	Osp. S. Maria della Misericordia	Perugia
Italy	A.O. Ospedali Riuniti Marche Nord	Pesaro
Italy	Ospedale Guglielmo da Saliceto	Piacenza
Italy	A.O. San Carlo	Potenza
Italy	Ospedale di Prato	Prato	PO
Italy	Ospedale Santa Maria delle Croci - AUSL	Ravenna
Italy	Ospedale Umberto I	Ravenna
Italy	Ospedale degli Infermi Rimini - Ospedale Cervesi Cattolica	Rimini
Italy	IRCCS Centro di Riferimento Oncologico Basilicata	Rionero in Vulture
Italy	Istituto Regina Elena	Roma
Italy	Ospedale Camillo Forlanini	Roma
Italy	Ospedale S. Giovanni Calibita Fatebenefratelli	Roma
Italy	Policlinico Universitario Campus Bio Medico	Roma
Italy	Ospedale di Sondrio	Sondrio
Italy	Ospedale Fabrizio Spaziani di Frosinone	Sora
Italy	Ospedale S. Chiara	Trento	TN
Italy	Ospedale Maggiore	Trieste
Italy	Azienda Ospedaliero-Universitaria S.M. della Misericordia di Udine	Udine
Italy	Ospedale S. Andrea	Vercelli
Italy	A.O.U. Integrata	Verona
Italy	Ospedale S. Bortolo ULSS 6, U.O. di Oncologia Medica	Vicenza	VI
Italy	ASL Viterbo - Ospedale Belcolle	Viterbo

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute, Naples

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	number and type of EGFR mutations in plasma samples	samples taken at baseline, 6 weeks, 6 months, and at progression	up to 2 years
Primary	progression free survival	as determined by investigator	up to 2 years
Primary	progression free survival	as determined by an independent central review board blinded to study treatment	up to 2 years
Secondary	overall survival		1 year
Secondary	changes in quality of life scores from baseline		up to 2 years
Secondary	number of patients with complete and partial responses , investigator assessed		6 months
Secondary	number of patients with complete and partial responses , centrally reviewed		6 months
Secondary	worst grade toxicity per patient		up to one year
Secondary	progression free survival according to type of EGFR mutation (exon 19del, exon 21L858R, other)		2 years