Clinical trial NCT02810457: Evaluation of FKB238 and Avastin in Patients With Advanced/Recurrent Non-squamous Non-small Cell Lung Cancer
Official title: A Randomised, Parallel, Double Blinded Study to Compare the Efficacy and Safety of FKB238 to Avastin® In 1st Line Treatment for Patients With Advanced/Recurrent Non Squamous NSCLC in Combination of Paclitaxel and Carboplatin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Cancer
Bevacizumab
Carboplatin
Paclitaxel
Lead sponsor: Centus Biotherapeutics Limited
Sponsor class: INDUSTRY
First posted: 2016-06-23
Enrollment: 731
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this research study is to compare the effectiveness and safety of FKB238 against Avastin® in men and women with advanced/recurrent non squamous non-small cell lung cancer


Eligibility criteria: Inclusion Criteria:

* Patients aged 18 years or older
* Newly diagnosed advanced (stage IV) /recurrent non-squamous NSCLC for which they had not received any systemic anti-cancer therapy for metastatic disease
* Histologically or cytologically confirmed diagnosis of predominantly non-squamous NSCLC
* Existence of at least 1 measurable lesion by RECIST v1.1
* Adequate hematological, renal and liver function
* Eastern Collaborative Oncology Group Performance Status (ECOG PS) 0 or 1
* Life expectancy longer than 6 months

Exclusion Criteria:

* Small cell lung cancer (SCLC) or combination SCLC and NSCLC. Squamous-cell tumors and mixed adenosquamous carcinomas of predominantly squamous nature
* Any unresolved toxicities from prior systemic therapy
* Known sensitizing epidermal growth factor receptor (EGFR) mutations or echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation positive mutations
* Previous dosing with vascular endothelial growth factor (VEGF) inhibitor
* Known hypersensitivity to any excipients of the Investigational Products (IPs) and combination chemotherapy
* Use of prohibited concomitant medication
* Known Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV) infection
* Fertile men or women of childbearing potential not using adequate contraception.

Other inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Overall Response Rate (ORR) Assessed as the Proportion of Patients With a Best Overall Response (BOR) of Either Complete Response (CR) or Partial Response (PR)
timeFrame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months.
Secondary outcomes:
measure: ORR at Week 19
timeFrame: From the date of randomization up to Week 19.
measure: Progression-free Survival (PFS)
timeFrame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months.
measure: Overall Survival (OS)
timeFrame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months.
measure: Duration Of Response (DOR)
timeFrame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months.
measure: Disease Control Rate (DCR) Assessed as the Proportion of Patients With a BOR of Either CR, PR, SD or NED
timeFrame: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months.
Other outcomes:
measure: Serum Trough Concentration (Ctrough)
timeFrame: Cycle 1 Day 1 (pre- and post-infusion), Cycle 2 Day 1 (pre), Cycle 4 Day 1 (pre and post), Cycle 6 Day 1 (pre), discontinuation visit, and every 12 weeks (up to 1 year [±14 days] after randomisation) until death, or the patient was lost to follow-up.
measure: Proportion of Patients Developing Anti-drug Antibodies (ADAs)
timeFrame: Pre-dose at Cycles 1, 2, 4 and 6, discontinuation visit, and every 12 weeks (up to 1 year [±14 days] after randomisation) until death, or the patient was lost to follow-up, whichever occurred first.
measure: Adverse Events (AEs)
timeFrame: From the time of signature of informed consent, throughout the treatment period and up to and including the 30-days after the last dose of study treatment, for a total estimated period of time of up to approximately 30 months.
measure: Vital Signs
timeFrame: Up to approximately 30 days after last dose of study treatment.
measure: Hematology
timeFrame: Up to approximately 30 days after last dose of study treatment.
measure: Clinical Chemistry
timeFrame: Up to approximately 30 days after last dose of study treatment.
measure: Urinalysis
timeFrame: Up to approximately 30 days after last dose of study treatment.
measure: Electrocardiogram
timeFrame: Up to approximately 30 days after last dose of study treatment.
measure: Eastern Collaborative Oncology Group Performance Status
timeFrame: Up to approximately 30 days after last dose of study treatment.
measure: Physical Examination
timeFrame: Up to approximately 30 days after last dose of study treatment.
Locations:
city: Fountain Valley
country: United States
facility: Research Site 7814 - Compassionate Care Research Group
state: California
city: Whittier
country: United States
facility: Research Site 7811 - Innovative Clinical Research Institute
state: California
city: Jacksonville
country: United States
facility: Research Site 7803 - 21st Century Oncology
state: Florida
city: Joliet
country: United States
facility: Research Site 7812 - Joliet Oncology-Hematology Associates, Ltd.
state: Illinois
city: Skokie
country: United States
facility: Research Site 7810 - Edward H. Kaplan, MD and Associates
state: Illinois
city: Minot
country: United States
facility: Research Site 7813 - Trinity Cancer Care Center
state: North Dakota
city: Canton
country: United States
facility: Research Site 7805 - Hematology & Oncology Associates, Inc.
state: Ohio
city: Canton
country: United States
facility: Research Site 7801 - Gabrail Cancer Center
state: Ohio
city: Massillon
country: United States
facility: Research Site 7804 - Tri-County Hematology & Oncology Associates, Inc.
state: Ohio
city: Houston
country: United States
facility: Research Site 7809 - Millennium Oncology
state: Texas
city: Olympia
country: United States
facility: Research Site 7806 - Vista Oncology Inc. PS
state: Washington
city: Brest
country: Belarus
facility: Research Site 8507
state: Brestskaya Voblasts
city: Grodno
country: Belarus
facility: Research Site 8505
state: Hrodzenskaya Voblasts
city: Mogilev
country: Belarus
facility: Research Site 8502
state: Mahilyowskaya Voblasts
city: Lesnoy
country: Belarus
facility: Research Site 8501
state: Minskaya Voblasts
city: Minsk
country: Belarus
facility: Research Site 8504
state: Minskaya Voblasts
city: Vitebsk
country: Belarus
facility: Research Site 8506
state: Vitsyebskaya Voblasts
city: Tuzla
country: Bosnia and Herzegovina
facility: Research Site 8605
state: Tuzlanski Kanton
city: Banja Luka
country: Bosnia and Herzegovina
facility: Research Site 8606
city: Mostar
country: Bosnia and Herzegovina
facility: Research Site 8602
city: Sarajevo
country: Bosnia and Herzegovina
facility: Research Site 8601
city: Sarajevo
country: Bosnia and Herzegovina
facility: Research Site 8603
city: Zenica
country: Bosnia and Herzegovina
facility: Research Site 8604
city: Sofia
country: Bulgaria
facility: Research Site 0905
state: Dobrich
city: Varna
country: Bulgaria
facility: Research Site 0904
city: Zagreb
country: Croatia
facility: Research Site 1802
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Research Site 1803
state: Grad Zagreb
city: Osijek
country: Croatia
facility: Research Site 1801
state: Osjecko-baranjska Županija
city: Bat'umi
country: Georgia
facility: Research Site 2504
state: Ajaria
city: Kutaisi
country: Georgia
facility: Research Site 2507
state: Imereti
city: Tbilisi
country: Georgia
facility: Research Site 2503
city: Tbilisi
country: Georgia
facility: Research Site 2505
city: Tbilisi
country: Georgia
facility: Research Site 2508
city: Würselen
country: Germany
facility: Research Site 2605
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Research Site 2603
state: Schleswig-Holstein
city: Hamburg
country: Germany
facility: Research Site 2604
city: Athens
country: Greece
facility: Research Site 3004
city: Thessaloniki
country: Greece
facility: Research Site 3003
city: Thessaloníki
country: Greece
facility: Research Site 3005
city: Gyula
country: Hungary
facility: Research Site 3303
state: Békés
city: Deszk
country: Hungary
facility: Research Site 3302
state: Csongrád
city: Mátraháza
country: Hungary
facility: Research Site 3301
state: Heves
city: Budapest
country: Hungary
facility: Research Site 3305
city: Budapest
country: Hungary
facility: Research Site 3304
city: Zalaegerszeg
country: Hungary
facility: Research Site 3306
city: Catania
country: Italy
facility: Research Site 4107
city: Piacenza
country: Italy
facility: Research Site 4106
city: Fukuyama-shi
country: Japan
facility: Research Site 4301
state: Hiroshima
city: Kumamoto-shi
country: Japan
facility: Research Site 4304
state: Kumamoto
city: Sasebo-shi
country: Japan
facility: Research Site 4303
state: Nagasaki
city: Busan
country: Korea, Republic of
facility: Research Site 6005
state: Busan Gwang'yeogsi
city: Suwon-si
country: Korea, Republic of
facility: Research Site 6004
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Research Site 6002
state: Seoul Teugbyeolsi
city: Ulsan
country: Korea, Republic of
facility: Research Site 6003
state: Ulsan Gwang'yeogsi
city: Arequipa
country: Peru
facility: Research Site 5402
city: Arequipa
country: Peru
facility: Research Site 5404
city: Lima
country: Peru
facility: Research Site 5401
city: Lima
country: Peru
facility: Research Site 5405
city: Cebu City
country: Philippines
facility: Research Site 5505
state: Cebu
city: Makati City
country: Philippines
facility: Research Site 5504
state: National Capital Region
city: Manila
country: Philippines
facility: Research Site 5501
state: National Capital Region
city: Manila
country: Philippines
facility: Research Site 5502
state: National Capital Region
city: Manila
country: Philippines
facility: Research Site 5506
state: National Capital Region
city: Quezon
country: Philippines
facility: Research Site 5503
city: Toruniak
country: Poland
facility: Research Site 5705
state: Kujawsko-pomorskie
city: Lodz
country: Poland
facility: Research Site 5708
state: Lódzkie
city: Krakow
country: Poland
facility: Research Site 5701
state: Malopolskie
city: Elblag
country: Poland
facility: Research Site 5702
state: Warminsko-mazurskie
city: Olsztyn
country: Poland
facility: Research Site 5706
state: Warminsko-mazurskie
city: Brzozów
country: Poland
facility: Research Site 5711
city: Nowy Sacz
country: Poland
facility: Research Site 5703
city: Cluj-Napoca
country: Romania
facility: Research Site 6105
state: Cluj
city: Cluj-Napoca
country: Romania
facility: Research Site 6106
state: Cluj
city: Floreşti
country: Romania
facility: Research Site 6108
state: Cluj
city: Baia Mare
country: Romania
facility: Research Site 6101
city: Constanta
country: Romania
facility: Research Site 6102
city: Craiova
country: Romania
facility: Research Site 6103
city: Iasi
country: Romania
facility: Research Site 6107
city: Arkhangelsk
country: Russian Federation
facility: Research Site 6209
state: Arkhangel'skaya Oblast'
city: Ufa
country: Russian Federation
facility: Research Site 6220
state: Bashkortostan, Respublika
city: Belgorod
country: Russian Federation
facility: Research Site 6221
state: Belgorodskaya Oblast'
city: Chelyabinsk
country: Russian Federation
facility: Research Site 6211
state: Chelyabinskaya Oblast'
city: Kuzmolovskiy
country: Russian Federation
facility: Research Site 6217
state: Leningradskaya Oblast'
city: Saransk
country: Russian Federation
facility: Research Site 6219
state: Mordoviya, Respublika
city: Moscow
country: Russian Federation
facility: Research Site 6225
state: Moskva
city: Moscow
country: Russian Federation
facility: Research Site 6203
state: Moskva
city: Novgorod
country: Russian Federation
facility: Research Site 6230
state: Nizhegorodskaya Oblast'
city: Novosibirsk
country: Russian Federation
facility: Research Site 6214
state: Novosibirskaya Oblast'
city: Novosibirsk
country: Russian Federation
facility: Research Site 6213
state: Novosibirskaya Oblast'
city: Omsk
country: Russian Federation
facility: Research Site 6215
state: Omskaya Oblast'
city: Omsk
country: Russian Federation
facility: Research Site 6224
state: Omskaya Oblast'
city: Orenburg
country: Russian Federation
facility: Research Site 6208
state: Orenburgskaya Oblast'
city: Rostov-on-Don
country: Russian Federation
facility: Research Site 6223
state: Rostovskaya Oblast'
city: Ryazan'
country: Russian Federation
facility: Research Site 6205
state: Ryazanskaya Oblast'
city: Samara
country: Russian Federation
facility: Research Site 6234
state: Samarskaya Oblast'
city: Saint Petersburg
country: Russian Federation
facility: Research Site 6235
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: Research Site 6212
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: Research Site 6216
state: Sankt-Peterburg
city: Saint Petersburg
country: Russian Federation
facility: Research Site 6201
state: Sankt-Peterburg
city: Sankt Petersburg
country: Russian Federation
facility: Research Site 6202
state: Sankt-Peterburg
city: Sankt Petersburg
country: Russian Federation
facility: Research Site 6210
state: Sankt-Peterburg
city: Izhevsk
country: Russian Federation
facility: Research Site 6229
state: Udmurtskaya Respublika
city: Kursk
country: Russian Federation
facility: Research Site 6228
city: Magnitogorsk
country: Russian Federation
facility: Research Site 6207
city: Saint Petersburg
country: Russian Federation
facility: Research Site 6222
city: Sremska Kamenica
country: Serbia
facility: Research Site 6401
state: Vojvodina
city: Belgrade
country: Serbia
facility: Research Site 6402
city: Belgrade
country: Serbia
facility: Research Site 6403
city: Belgrade
country: Serbia
facility: Research Site 6404
city: Belgrade
country: Serbia
facility: Research Site 6405
city: Kragujevac
country: Serbia
facility: Research Site 6406
state: Šumadijski Okrug
city: A Coruna
country: Spain
facility: Research Site 7004
state: A Coruña
city: Castellón De La Plana
country: Spain
facility: Research Site 7002
state: Castellon
city: Cordoba
country: Spain
facility: Research Site 7005
state: Córdoba
city: Jaen
country: Spain
facility: Research Site 7009
state: Jaén
city: Burgos
country: Spain
facility: Research Site 7001
city: Madrid
country: Spain
facility: Research Site 7007
city: Murcia
country: Spain
facility: Research Site 7008
city: Murcia
country: Spain
facility: Research Site 7003
city: New Taipei City
country: Taiwan
facility: Research Site 7402
state: Taipei
city: Douliu
country: Taiwan
facility: Research Site 7404
state: Yunlin
city: Changhua
country: Taiwan
facility: Research Site 7403
city: Taipei
country: Taiwan
facility: Research Site 7401
city: Bangkok
country: Thailand
facility: Research Site 7506
state: Krung Thep Maha Nakhon
city: Hat Yai
country: Thailand
facility: Research Site 7501
state: Songkhla
city: Bangkok
country: Thailand
facility: Research Site 7504
city: Chiang Mai
country: Thailand
facility: Research Site 7507
city: Chiang Rai
country: Thailand
facility: Research Site 7505
city: Khon Kaen
country: Thailand
facility: Research Site 7503
city: Udon Thani
country: Thailand
facility: Research Site 7502
city: Ankara
country: Turkey
facility: Research Site 7607
city: İzmir
country: Turkey
facility: Research Site 7605
city: Izmir
country: Turkey
facility: Research Site 7601
city: Malatya
country: Turkey
facility: Research Site 7606
city: Chernivtsi
country: Ukraine
facility: Research Site 7702
state: Chernivets'ka Oblast'
city: Kharkiv
country: Ukraine
facility: Research Site 7705
state: Kharkivs'ka Oblast'
city: Odesa
country: Ukraine
facility: Research Site 7706
state: Odes'ka Oblast'
city: Lutsk
country: Ukraine
facility: Research Site 7713
state: Volyns'ka Oblast'
city: Uzhgorod
country: Ukraine
facility: Research Site 7707
state: Zakarpats'ka Oblast'
city: Dnipropetrovs'k
country: Ukraine
facility: Research Site 7709
city: Ivano-Frankivs'k
country: Ukraine
facility: Research Site 7701
city: Kryvyi Rih
country: Ukraine
facility: Research Site 7708
city: Kyiv
country: Ukraine
facility: Research Site 7704
city: Sumy
country: Ukraine
facility: Research Site 7710
city: Hanoi
country: Vietnam
facility: Research Site 8401
state: Ha Noi, Thu Do
city: Hanoi
country: Vietnam
facility: Research Site 8402
state: Ha Noi, Thu Do
city: Hanoi
country: Vietnam
facility: Research Site 8405
state: Ha Noi, Thu Do
Study officials:
affiliation: Centus Biotherapeutics Limited
name: Centus Biotherapeutics Limited
role: STUDY_DIRECTOR
References:
citation: Syrigos K, Abert I, Andric Z, Bondarenko IN, Dvorkin M, Galic K, Galiulin R, Kuchava V, Sriuranpong V, Trukhin D, Zhavrid E, Fu D, Kassalow LM, Jones S, Bashir Z; AVANA Investigators. Efficacy and Safety of Bevacizumab Biosimilar FKB238 Versus Originator Bevacizumab: Results from AVANA, a Phase III Trial in Patients with Non-Squamous Non-Small-Cell Lung Cancer (non-sq-NSCLC). BioDrugs. 2021 Jul;35(4):417-428. doi: 10.1007/s40259-021-00489-4. Epub 2021 Jul 15.