Clinical trial • Phase II • Oncology

Bevacizumab for Advanced non-small cell lung cancer

Phase II trial of Bevacizumab for Advanced non-small cell lung cancer.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Advanced non-small cell lung cancer
Trial Stage
Phase II
Drug Modality
Monoclonal antibody

Key dates

Initial CTIS Submission Date
26-09-2024
First CTIS Authorization Date
26-11-2024

Trial design

Randomised, atezolizumab (tecentriq) versus atezolizumab (tecentriq) + bevacizumab (avastin); doses/schedule not specified in the record-controlled Phase II trial across 32 sites in Italy.

Randomised
Yes
Comparator
Atezolizumab (Tecentriq) versus Atezolizumab (Tecentriq) + Bevacizumab (Avastin); doses/schedule not specified in the record
Target Sample Size
130

Eligibility

Recruits 130 Vulnerable population not selected. Written informed consent is required from participants; no assent or parental consent procedures for minors are described (trial enrolment restricted to adults)..

Pregnancy Exclusion
8. Pregnancy or lactating women who are pregnant, lactating, or intending to become pregnant during the study.
Vulnerable Population
Vulnerable population not selected. Written informed consent is required from participants; no assent or parental consent procedures for minors are described (trial enrolment restricted to adults).

Inclusion criteria

  • {"criterion_text":"- 1) Histologically confirmed diagnosis of stage IV non-squamous NSCLC with no evidence of EGFR sensitizing mutations or ALK or ROS1 rearrangements.\n- 2) Availability of tumor tissue.\n- 3) 3) Evidence of high levels of PD-L1 expression evaluated with immunohistochemistry (=50% by 22C3 or SP263 or TC/IC 3 scoring by SP 142) .\n- 4) No previous chemotherapy. Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last dose of chemotherapy and/or radiotherapy.\n- 5) ECOG performance status 0-1.\n- 6) Life expectancy > 3 months\n- 7) Age =18 years.\n- 8) Measurable disease, as defined by RECIST v1.1.\n- 9) Adequate hematologic and organ function, defined by the following laboratory results obtained within 28 days prior to randomization: o ANC = 1500 cells/µL without granulocyte colony-stimulating factor support o Platelet count = 100,000/µL without transfusion o Hemoglobin = 9.0 g/dL Patients may be transfused to meet this criterion o AST, ALT, and alkaline phosphatase = 2.5 × ULN, with the following exceptions: ¿ Patients with documented liver metastases: AST and/or ALT = 5 × ULN ¿ Patients with documented liver or bone metastases: alkaline phosphatase = 5 × ULN. o Serum bilirubin = 1.25 × ULN o Patients with known Gilbert disease who have serum bilirubin level = 3 mg/dL may be enrolled o Calculated creatinine clearance (CRCL) = 45 mL/min or calculated CRCL must be = 60 mL/min\n- 10) Patient compliance to trial procedures.\n- 11) Written informed consent."}

Exclusion criteria

  • {"criterion_text":"- 1. No tumor tissue available.\n- 2. PD-L1 expression < 50 % or PD-L1 expression unknown or not assessable\n- 3. Patient positive for EGFR mutations or ALK or ROS1 rearrangements.\n- 4. Patients with squamous histology or with specific contraindication to bevacizumab therapy.\n- 5. Previously treated with chemotherapy\n- 6. Concomitant radiotherapy or chemotherapy.\n- 7. Previous therapy with any checkpoint inhibitor.\n- 8. Pregnancy or lactating women who are pregnant, lactating, or intending to become pregnant during the study.\n- 9. Symptomatic brain metastases\n- 10. Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression\n- 11. Leptomeningeal disease.\n- 12. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures\n- 13. Uncontrolled or symptomatic hypercalcemia\n- 14. Malignancies other than NSCLC within 5 years prior to randomization\n- 15. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins\n- 16. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells\n- 17. History of autoimmune disease\n- 18. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.\n- 19. Positive test for HIV\n- 20. Patients with active hepatitis B or hepatitis C.\n- 21. Active tuberculosis\n- 22. Severe infections within 4 weeks prior to randomization\n- 23. Significant cardiovascular disease\n- 24. Major surgical procedure other than for diagnosis within 28 days prior to randomization\n- 25. Prior allogeneic bone marrow transplantation or solid organ transplant\n- 26. Administration of a live, attenuated vaccine within 4 weeks before randomization\n- 27. metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease\n- 28. Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment\n- 29. Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to randomization\n- 30. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, antiPD-1, and anti-PD-L1 therapeutic antibodies\n- 31. Treatment with systemic immunostimulatory agents\n- 32. Treatment with systemic immunosuppressive medications\n- 33. Patients who have received acute, low-dose, systemic immunosuppressant medications\n- 34. The use of steroids are permitted only as inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, low-dose supplemental corticosteroids for adrenocortical insufficiencyand corticosteroids for CT pre treatment.\n- 35. Inadequately controlled hypertension\n- 36. Prior history of hypertensive crisis or hypertensive encephalopathy\n- 37. Significant vascular disease\n- 38. History of hemoptysis (= one-half teaspoon of bright red blood per episode) within 1 month prior to randomization;\n- 39. Current or recent use of aspirin or treatment with dipyramidole, ticlopidine, clopidogrel, and clostazol\n- 40. Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes that has not been stable for > 2 weeks prior to randomization\n- 41. Prophylactic anticoagulation for the patency of venous access devices is allowed\n- 42. Prophylactic use of low-molecular-weight heparin\n- 43. Core biopsy or other minor surgical procedure, excluding placement of a vascular access device,\n- 44. History of abdominal or tracheosphageal fistula or gastrointestinal perforation\n- 45. Serious, non-healing wound, active ulcer, or untreated bone fracture\n- 46. Proteinuria\n- 47. Known sensitivity to any component of bevacizumab E.5 - End Points"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Overall Survival (OS) in patients treated with atezolizumab alone versus atezolizumab-bevacizumab combination","definition_or_measurement_approach":""}

Recruitment

Planned Sample Size
130
Recruitment Window Months
70
Consent Approach
Written informed consent required from participants ("Written informed consent" listed in inclusion criteria). Subject information and informed consent form documents are provided (documents titled in the record). No assent or parental consent processes for minors are described; trial enrolment limited to adults.

Geography

Total Number Of Sites
32
Total Number Of Participants
130

Italy

Earliest CTIS Part Ii Submission Date
18-09-2024
Latest Decision Or Authorization Date
05-08-2025
Processing Time Days
321
Number Of Sites
32
Number Of Participants
130

Sites

Site Name
Istituto Tumori Bari Giovanni Paolo II
Department Name
alugini@hsangiovanni.roma.it
Principal Investigator Name
Michele Montrone
Principal Investigator Email
galetta@oncologico.bari.it
Contact Person Name
Michele Montrone
Contact Person Email
galetta@oncologico.bari.it
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
Oncoematologia
Principal Investigator Name
Stefano Tamberi
Principal Investigator Email
stefano.tamberi@auslromagna.it
Contact Person Name
Stefano Tamberi
Contact Person Email
stefano.tamberi@auslromagna.it
Site Name
La Maddalena S.p.A.
Department Name
UO Oncologia Medica
Principal Investigator Name
Vittorio Gebbia
Principal Investigator Email
vittorio.gebbia@gmail.com
Contact Person Name
Vittorio Gebbia
Contact Person Email
vittorio.gebbia@gmail.com
Site Name
Azienda Unita Sanitaria Locale Di Piacenza
Department Name
Oncologia Medica
Principal Investigator Name
Elena Zaffignani
Principal Investigator Email
e.zaffignani@ausl.pc.it
Contact Person Name
Elena Zaffignani
Contact Person Email
e.zaffignani@ausl.pc.it
Site Name
Azienda Unita' Sanitaria Locale Toscana Sud Est
Department Name
Oncologia Medica
Principal Investigator Name
Silvia Catanese
Principal Investigator Email
carmelo.bengala@uslsudest.toscana.it
Contact Person Name
Silvia Catanese
Site Name
I.F.O. Istituti Fisioterapici Ospitalieri
Department Name
UOC Oncologia Medica 2
Principal Investigator Name
Federico Cappuzzo
Principal Investigator Email
federico.cappuzzo@ifo.gov.it
Contact Person Name
Federico Cappuzzo
Contact Person Email
federico.cappuzzo@ifo.gov.it
Site Name
Fondazione IRCCS San Gerardo Dei Tintori
Department Name
UO Oncologia Medica
Principal Investigator Name
Diego Cortinovis
Principal Investigator Email
d.cortinovis@asst-monza.it
Contact Person Name
Diego Cortinovis
Contact Person Email
d.cortinovis@asst-monza.it
Site Name
Azienda Socio Sanitaria Territoriale Dei Sette Laghi
Department Name
Oncologia Medica
Principal Investigator Name
Francesco Grossi
Principal Investigator Email
alessandro.tuzi@asst-settelaghi.it
Contact Person Name
Francesco Grossi
Site Name
Ospedale "A. Perrino"
Department Name
UOC Oncologia Medica
Principal Investigator Name
Saverio Cinieri
Principal Investigator Email
saverio.cinieri@me.com
Contact Person Name
Saverio Cinieri
Contact Person Email
saverio.cinieri@me.com
Site Name
IRCCS Ospedale Sacro Cuore Don Calabria
Department Name
Oncologia Medica
Principal Investigator Name
Stefania Gori
Principal Investigator Email
stefania.gori@sacrocuore.it
Contact Person Name
Stefania Gori
Contact Person Email
stefania.gori@sacrocuore.it
Site Name
Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I G M Lancisi G Salesi
Department Name
Oncologia medica
Principal Investigator Name
Rossana Berardi
Principal Investigator Email
r.berardi@univpm.it
Contact Person Name
Rossana Berardi
Contact Person Email
r.berardi@univpm.it
Site Name
Azienda Unita Locale Socio Sanitaria N. 1 Dolomiti
Department Name
Oncologia Medica
Principal Investigator Name
Petros Giovanis
Principal Investigator Email
petros.giovanis@aulss1.veneto.it
Contact Person Name
Petros Giovanis
Site Name
Azienda Ospedaliera S Giovanni Addolorata
Department Name
Oncologia Medica
Principal Investigator Name
Andrea Lugini
Principal Investigator Email
alugini@hsangiovanni.roma.it
Contact Person Name
Andrea Lugini
Contact Person Email
alugini@hsangiovanni.roma.it
Site Name
Azienda Ospedaliera Universitaria Integrata Verona
Department Name
Oncologia
Principal Investigator Name
Sara Pilotto
Principal Investigator Email
sara.pilotto.85@gmail.com
Contact Person Name
Sara Pilotto
Contact Person Email
sara.pilotto.85@gmail.com
Site Name
Ospedale “Giuseppe Mazzini” - Teramo
Department Name
Oncologia Medica
Principal Investigator Name
Katia Cannita
Principal Investigator Email
katia.cannita@aslteramo.it
Contact Person Name
Katia Cannita
Contact Person Email
katia.cannita@aslteramo.it
Site Name
Ospedale S G Moscati
Department Name
SC di Oncologia Medica
Principal Investigator Name
Salvatore Pisconti
Principal Investigator Email
salvatore.pisconti@asl.taranto.it
Contact Person Name
Salvatore Pisconti
Site Name
Ospedale Generale Provinciale Di Macerata
Department Name
UOC Oncologia
Principal Investigator Name
Nicola Battelli
Principal Investigator Email
battellin@gmail.com
Contact Person Name
Nicola Battelli
Contact Person Email
battellin@gmail.com
Site Name
Azienda Sanitaria Locale Della Provincia Di Biella
Department Name
SC di Oncologia
Principal Investigator Name
Roberta Gauna
Principal Investigator Email
lisa.pietrogiovanna@aslbi.piemonte.it
Contact Person Name
Roberta Gauna
Site Name
Alessandro Manzoni Hospital
Department Name
UOC Oncologia
Principal Investigator Name
Isabella Vittimberga
Principal Investigator Email
i.vittimberga@asst-lecco.it
Contact Person Name
Isabella Vittimberga
Contact Person Email
i.vittimberga@asst-lecco.it
Site Name
Azienda Sanitaria Provinciale di Siracusa
Department Name
UOC Oncologia Medica
Principal Investigator Name
Paolo Tralongo
Principal Investigator Email
paolo.tralongo@asp.sr.it
Contact Person Name
Paolo Tralongo
Contact Person Email
paolo.tralongo@asp.sr.it
Site Name
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
Department Name
Oncologia Medica
Principal Investigator Name
Hector Soto Parra
Principal Investigator Email
hsotoparra.ctu@gmail.com
Contact Person Name
Hector Soto Parra
Contact Person Email
hsotoparra.ctu@gmail.com
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
SSD Oncologia Toracica
Principal Investigator Name
Angelo Delmonte
Principal Investigator Email
angelo.delmonte@irst.emr.it
Contact Person Name
Angelo Delmonte
Contact Person Email
angelo.delmonte@irst.emr.it
Site Name
Azienda Sanitaria Locale Roma 4
Department Name
UOSD Oncologia
Principal Investigator Name
Mario Rosario D'Andrea
Principal Investigator Email
mariorosario.dandrea@aslroma4.it
Contact Person Name
Mario Rosario D'Andrea
Site Name
Azienda Ospedaliera Policlinico Universitario Tor Vergata
Department Name
Oncoematologia
Principal Investigator Name
Mario Roselli
Principal Investigator Email
mario.roselli@uniroma2.it
Contact Person Name
Mario Roselli
Contact Person Email
mario.roselli@uniroma2.it
Site Name
Azienda USL IRCCS Di Reggio Emilia
Department Name
Oncologia Medica
Principal Investigator Name
Francesca Zanelli
Principal Investigator Email
francesca.zanelli@ausl.re.it
Contact Person Name
Francesca Zanelli
Contact Person Email
francesca.zanelli@ausl.re.it
Site Name
Azienda Ospedaliera Dei Colli Ospedale Monaldi
Department Name
U.O.C. di Pneumologia ad indirizzo oncologico
Principal Investigator Name
Danilo Rocco
Principal Investigator Email
danilorocc@yahoo.it
Contact Person Name
Danilo Rocco
Contact Person Email
danilorocc@yahoo.it
Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Department Name
Oncologia
Principal Investigator Name
Silvia Novello
Principal Investigator Email
silvia.novello@unito.it
Contact Person Name
Silvia Novello
Contact Person Email
silvia.novello@unito.it
Site Name
Azienda Ospedaliero Universitaria Di Modena
Department Name
Dipartimento di oncologia ed ematologia
Principal Investigator Name
Federica Bertolini
Principal Investigator Email
barbieri.fausto@policlinico.mo.it
Contact Person Name
Federica Bertolini
Site Name
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Department Name
UOC Oncologia Medica
Principal Investigator Name
Claudia Bareggi
Principal Investigator Email
francesco.grossi@policlinico.mi.it
Contact Person Name
Claudia Bareggi
Site Name
San Camillo Forlanini Hospital
Department Name
Oncologia
Principal Investigator Name
Serena Ricciardi
Principal Investigator Email
mrmiglio53@gmail.com
Contact Person Name
Serena Ricciardi
Contact Person Email
mrmiglio53@gmail.com
Site Name
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Department Name
Oncologia Medica per le malattie toraciche
Principal Investigator Name
Alessandro Morabito
Principal Investigator Email
a.morabito@istitutotumori.na.it
Contact Person Name
Alessandro Morabito
Site Name
IRCCS CROB
Department Name
UO di Oncologia Medica
Principal Investigator Name
Vittoria Lapadula
Principal Investigator Email
michele.aieta@crob.it
Contact Person Name
Vittoria Lapadula
Contact Person Email
michele.aieta@crob.it

Sponsor

Primary sponsor

Full Name
Fondazione Ricerca Traslazionale
Organisation Type
Laboratory/Research/Testing facility
Country Of Registered Address
Italy

Investigational products

Investigational Product Name
Avastin 25 mg/ml concentrate for solution for infusion.
Active Substance
Bevacizumab
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENOUS
Route
Intravenous
Authorisation Status
Marketing authorisation EU/1/04/300/001 (authorised)
Maximum Dose
15 mg/Kg
Investigational Product Name
Tecentriq 1 200 mg concentrate for solution for infusion
Active Substance
Atezolizumab
Modality
Monoclonal antibody
Routes Of Administration
INTRAVENIOUS INFUSION
Route
Intravenous
Authorisation Status
Marketing authorisation EU/1/17/1220/001 (authorised)
Maximum Dose
1200 mg
Combination Treatment
Yes

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