Study Comparing Bevacizumab + Erlotinib vs Erlotinib Alone as First Line Treatment of Patients With EGFR Mutated Advanced Non Squamous Non Small Cell Lung Cancer
- Conditions
- Non-squamous Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT02633189
- Lead Sponsor
- National Cancer Institute, Naples
- Brief 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.
- Detailed Description
The co-primary objectives are to assess investigator-assess, and blinded independent centrally-reviewed progression-free survival .
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 200
- Age ≥18 years
- Histological documentation of primary non squamous lung carcinoma
- Stage IV or IIIB disease with supraclavicular 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.
-
EGFR T790M mutation alone or exon 20 insertions as unique mutation
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Tumors with a squamous component
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Prior chemotherapy or any other medical treatment for advanced NSCLC (previous neoadjuvant or adjuvant chemotherapy is allowed if > 6 months before randomisation)
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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)
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Full-dose anticoagulation with warfarin
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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
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Receiving any medications or substances that are strong or moderate inhibitors of cytochrome P450 3A4 (CYP3A4) are prohibited =< 7 days prior to registration
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Receiving any medications or substances that are inducers of CYP3A4 use of inducers are prohibited =< 7 days prior to registration
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Inadequate coagulation parameters:
- activated partial thromboplastin time (APTT) >1.5 x the upper limit of normal (ULN) or
- INR >1.5
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Inadequate liver function, defined as:
- serum (total) bilirubin >1.5 x ULN
- AST/SGOT or ALT/SGPT >2.5 x ULN
-
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.
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Pregnancy or breast-feeding
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Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure >100 mmHg on antihypertensive medications)
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History of gross hemoptysis within 3 months prior to randomization unless definitively treated with surgery or radiation
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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
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Serious, non-healing wound, ulcer, or bone fracture
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Evidence of bleeding diathesis or coagulopathy or other serious or acute internal bleeding within 6 months prior to randomization
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Central Nervous System (CNS) bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months
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In-patient surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization
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Minor surgical procedure, fine needle aspirations or core biopsy within 7 days prior to randomization
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Anticipation of need for a major surgical procedure during the course of the study
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Inability to take oral medication or requirement for intravenous (IV) alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption
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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
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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)
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Brain metastasis
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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
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Known HIV positive patients (patients with both acute or chronic infection are excluded)
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Active HBV or HCV infection (patients with chronic non-active infection are eligible)
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Any already known inflammatory changes of the surface of the eye at baseline
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Any other concomitant pathologies or laboratory alterations that prevent or contraindicate the use of erlotinib or bevacizumab.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description erlotinib Erlotinib - erlotinib and bevacizumab Erlotinib - erlotinib and bevacizumab Bevacizumab -
- Primary Outcome Measures
Name Time Method progression free survival up to 2 years as determined by an independent central review board blinded to study treatment
- Secondary Outcome Measures
Name Time Method overall survival 1 year changes in quality of life scores from baseline up to 2 years worst grade toxicity per patient up to one year progression free survival according to type of EGFR mutation (exon 19del, exon 21L858R, other) 2 years number of patients with complete and partial responses , investigator assessed 6 months number of patients with complete and partial responses , centrally reviewed 6 months
Trial Locations
- Locations (55)
Ospedale Maggiore
🇮🇹Trieste, Italy
A.O.U. Integrata
🇮🇹Verona, Italy
A.S.O. SS Antonio e Biagio e Cesare Arrigo
🇮🇹Alessandria, Italy
Ospedale di Prato
🇮🇹Prato, PO, Italy
A.O. S. Giuseppe Moscati
🇮🇹Avellino, Italy
Ospedale Ramazzini, Day Hospital Oncologico
🇮🇹Carpi, MO, Italy
Fondazione Salvatore Maugeri
🇮🇹Pavia, Italy
A.O. San Carlo
🇮🇹Potenza, Italy
Ospedale Fabrizio Spaziani di Frosinone
🇮🇹Sora, Italy
IRCCS Centro di Riferimento Oncologico Basilicata
🇮🇹Rionero in Vulture, Italy
Ospedale Guglielmo da Saliceto
🇮🇹Piacenza, Italy
Ospedale S. Chiara
🇮🇹Trento, TN, Italy
Istituto Oncologico Veneto
🇮🇹Padova, Italy
Policlinico vittorio Emanuele
🇮🇹Catania, Italy
Casa di Cura La Maddalena S.p.A., Dipartimento Oncologico
🇮🇹Palermo, PA, Italy
Ospedale S. Bortolo ULSS 6, U.O. di Oncologia Medica
🇮🇹Vicenza, VI, Italy
Ospedale A. cardarelli
🇮🇹Campobasso, Italy
AO G. Rummo
🇮🇹Benevento, Italy
Centro Riferimento Oncologico
🇮🇹Aviano, Italy
Ospedale Senatore Antonio Perrino
🇮🇹Brindisi, Italy
U.L.S.S. 15 Veneto
🇮🇹Camposampiero, Italy
Ospedale S. Croce
🇮🇹Fano, Italy
Istituto Nazionale Tumori Fondazione G. Pascale
🇮🇹Napoli, Italy
Centro Clinico Diagnostico G.B. Morgagni
🇮🇹Catania, Italy
A.O. Garibaldi Nesima
🇮🇹Catania, Italy
Ospedale Civile per gli Infermi
🇮🇹Faenza, 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 Europeo di Oncologia
🇮🇹Milano, Italy
A.O.U. Policlinico Modena
🇮🇹Modena, Italy
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
🇮🇹Meldola, Italy
Ospedale San Paolo
🇮🇹Milano, Italy
A.O. U.L.S.S. 13
🇮🇹Mirano, Italy
Istituto Nazionale Tumori
🇮🇹Milano, Italy
Azienda Ospedaliera Cardarelli
🇮🇹Napoli, Italy
A.O.U. Seconda Università di Napoli
🇮🇹Napoli, Italy
AORN Ospedale dei Colli - Osp Monaldi
🇮🇹Napoli, Italy
Istituto Sacro Cuore Don Calabria
🇮🇹Negrar, Italy
A.O.U. Maggiore della CaritÃ
🇮🇹Novara, Italy
Policlinico Giaccone
🇮🇹Palermo, Italy
A.O. Ospedali Riuniti Marche Nord
🇮🇹Pesaro, Italy
Osp. S. Maria della Misericordia
🇮🇹Perugia, Italy
Ospedale Umberto I
🇮🇹Ravenna, Italy
Ospedale degli Infermi Rimini - Ospedale Cervesi Cattolica
🇮🇹Rimini, Italy
Ospedale Santa Maria delle Croci - AUSL
🇮🇹Ravenna, Italy
Istituto Regina Elena
🇮🇹Roma, Italy
Ospedale Camillo Forlanini
🇮🇹Roma, Italy
Policlinico Universitario Campus Bio Medico
🇮🇹Roma, Italy
Ospedale S. Giovanni Calibita Fatebenefratelli
🇮🇹Roma, Italy
Ospedale di Sondrio
🇮🇹Sondrio, Italy
Azienda Ospedaliero-Universitaria S.M. della Misericordia di Udine
🇮🇹Udine, Italy
Ospedale S. Andrea
🇮🇹Vercelli, Italy
ASL Viterbo - Ospedale Belcolle
🇮🇹Viterbo, Italy