Phase III Trial BI 695502 Plus Chemotherapy vs. Avastin® Plus Chemotherapy in Patients With Lung Cancer
A Multicenter, Randomized, Double-blind Phase III Trial to Evaluate Efficacy and Safety of BI 695502 Plus Chemotherapy Versus Avastin® Plus Chemotherapy in Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer
2 other identifiers
interventional
671
28 countries
189
Brief Summary
The objective of this phase III trial is to establish statistical equivalence in terms of efficacy (best overall response rate \[ORR\], proportion of patients with complete response \[CR\] plus partial response \[PR\]) until 18 weeks of first-line treatment with BI 695502 plus chemotherapy versus Avastin® plus chemotherapy followed by maintenance monotherapy with either BI 695502 or Avastin®.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jul 2015
Typical duration for phase_3
189 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 21, 2014
CompletedFirst Posted
Study publicly available on registry
October 23, 2014
CompletedStudy Start
First participant enrolled
July 8, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
November 16, 2018
CompletedResults Posted
Study results publicly available
January 13, 2020
CompletedJanuary 13, 2020
December 1, 2019
2 years
October 21, 2014
November 15, 2019
December 26, 2019
Conditions
Outcome Measures
Primary Outcomes (1)
Best Overall Response Rate (ORR), Based on Unconfirmed Response Assessment, as Assessed by Central Imaging Review Until 18 Weeks After the Start of Treatment
ORR was defined as the percentage of patients who achieved at least one visit response of complete response (CR) or partial response (PR) after the start of treatment. The response criteria evaluation was carried out according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. CR and PR did not need to be confirmed by a subsequent tumor assessment due to blinded central assessment. CR: Disappearance of all target lesions since baseline; PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Tumor assessments were performed prior to trial drug administration, until 18 weeks.
Tumor assessment scans were performed at baseline, Cycle 3 (Week 6), Cycle 5 (Week 12) and at Week 18 ±14 days. Best ORR evaluated until confirmed disease progression, unacceptable toxicity, death or up to 18 weeks, whichever happened earlier.
Secondary Outcomes (4)
Percentage of Patients With Selected Treatment-Emergent Adverse Events (TEAEs) For Comparability Assessment of BI 695502 and US-licensed Avastin®
From first dose of trial drug until 16 weeks after the last dose of trial medication, up to 218 days.
Progression-Free Survival (PFS) Time as Determined by Investigator Assessment
Tumor scans performed at baseline, Cycle 3 (Week 6), Cycle 5 (Week 12), Cycle 7 (Week 18), then every 3 cycles (~9 weeks) until confirmed disease progression. Analysis performed for pre-switch period only; maximum duration of up to 35 cycles (105 weeks).
Overall Survival (OS) Time
From baseline until death due to any cause, ie., up to 35 cycles (105 weeks).
Duration of Response (DOR) as Determined by Investigator Assessment
Tumor scans performed at baseline, Cycle 3 (Week 6), Cycle 5 (Week 12), Cycle 7 (Week 18), then every 3 cycles (~9 weeks) until confirmed disease progression., ie up to 35 cycles (105 weeks).
Study Arms (2)
BI 695502
EXPERIMENTALAvastin
ACTIVE COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- Adult patients aged \>=18 years with histologically or cytologically confirmed advanced nonsquamous non-small cell lung cancer (nsNSCLC). Mixed tumors should be categorized according to the predominant histology.
- Note: NSCLC should be predominantly nonsquamous. Recurrent or metastatic disease (Stage IV) with an indication for therapy with paclitaxel + carboplatin + Avastin®.
- Patients harboring tumors with unknown or without activating epidermal growth factor receptor (EGFR) / anaplastic lymphoma receptor tyrosine kinase (ALK) mutation maybe included provided chemotherapy is standard of care. At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on independent central review.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
- Adequate hepatic, renal, and bone marrow function:
You may not qualify if:
- Prior therapy with monoclonal antibodies or small molecule inhibitors against Vascular Endothelial Growth Factor (VEGF) or VEGF receptors, including Avastin®.
- Prior systemic therapy for metastatic disease. Prior systemic anticancer therapy or radiotherapy for locally advanced nsNSCLC if completed \<12 months prior to Screening.
- Previous malignancy other than NSCLC in the last 5 years except for basal cell cancer of the skin or pre-invasive cancer of the cervix.
- Symptomatic brain metastasis. Diagnosis of small cell carcinoma of the lung, squamous cell carcinoma of the lung, NSCLC not specified (NS) or NSCLC not otherwise specified(NOS).
- Any unresolved toxicity \> Common Toxicity Criteria Grade 1 (except alopecia) from previous anticancer therapy (including radiotherapy).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (189)
Pacific Cancer Medical Center, Inc.
Anaheim, California, 92801, United States
Comprehensive Blood and Cancer Center
Bakersfield, California, 93309, United States
Lalita Pandit, M.D., Inc.
Fountain Valley, California, 92708, United States
Southern California Oncology Research Alliance
Los Angeles, California, 90057, United States
Innovative Clinical Research, Inc.
Whittier, California, 90603, United States
Ashland Bellefonte Cancer Center
Ashland, Kentucky, 41101, United States
Reliant Medical Group
Worcester, Massachusetts, 01608, United States
Detroit Clinical Research Center
Owosso, Michigan, 48867, United States
Carolinas Cancer Care
Charlotte, North Carolina, 28204-2839, United States
CENIT - Centro de Neurociencias, Investigacion y Tratamiento
Ciudad Autonoma Buenos Aires, C1125ABD, Argentina
Sanatorio Delta
Rosario, S2000BIF, Argentina
Sanatorio Parque
Rosario, S2000DSV, Argentina
Centro Oncológico de Rosario
Rosario, S2000KZE, Argentina
CPCO - Centro de Pesquisa Clinica em Oncologia
Cachoeiro de Itapemirim, 29308-014, Brazil
Hospital do Cancer do Ceara
Fortaleza, 60430-230, Brazil
Pronutrir
Fortaleza, 60810-180, Brazil
Hospital de Carida de de Ijui - CACON
Ijuí, 98700-000, Brazil
Hospital Bruno Born
Lajeado, 95900-000, Brazil
Hospital da Cidade de Passo Fundo
Passo Fundo, 99010-260, Brazil
Universidade de Caxias do Sul - IPCEM - Inst. de Pesq.clilni
Petrópolis, 95070-560, Brazil
Irmandade da Santa Casa de Misericórdia de Porto Alegre
Porto Alegre, 90035-074, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre, 90035-903, Brazil
CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
Santo André, 09060-650, Brazil
ICAVC - Instituto do Cancer Arnaldo Vieira de Carvalho
São Paulo, 01209-000, Brazil
ICESP - Instituto do Cancer do Estado de Sao Paulo
São Paulo, 01246-000, Brazil
Clinica de Oncologia de Sorocaba
Sorocaba, 18030-075, Brazil
MHAT - Dobrich, AD
Dobrich, 9300, Bulgaria
UMHAT Georgi Stranski, Clinic of Paediatrics, Pleven
Pleven, 5800, Bulgaria
Complex Oncological Center - Plovdiv, EOOD
Plovdiv, 4004, Bulgaria
DCC 1 - Ruse, EOOD
Rousse, 7002, Bulgaria
MHAT Serdika, EOOD, Sofia
Sofia, 1303, Bulgaria
MHAT 'Tokuda Hospital Sofia', EAD
Sofia, 1407, Bulgaria
SHATOD 'Dr. Marko Antonov Markov'-Varna, EOOD
Varna, 9010, Bulgaria
Clínica Santa María
Santiago, 7520349, Chile
Hospital Clínico San Borja Arriarán
Santiago, 8360160, Chile
Centro Internacional de Estudios Clinicos - CIEC
Santiago, 8420383, Chile
Instituto Clínico Oncológico del Sur - ICOS
Temuco, 4810469, Chile
Hospital Clinico Viña del Mar
Viña del Mar, 1741, Chile
General Hospital Pula
Pula, 52100, Croatia
Clinical Hospital Centar Sestre Milosrdnice
Zagreb, 10000, Croatia
University Clinic for Pulmonary Diseases
Zagreb, 10000, Croatia
Oncology Centre- Mansoura University
Al Mansurah, 1234, Egypt
Alexandria University Hospital
Alexandria, 21131, Egypt
Ain Shams University Hospital
Cairo, 11566, Egypt
National Cancer Institute, Cairo University
Cairo, 11796, Egypt
Nasser Institute
Cairo, 12655, Egypt
Menofiya University Hospital
Monofia, 31111, Egypt
Gesundheitszentrum Wetterau gGmbH
Bad Nauheim, 61231, Germany
Athens Hospital of Chest Diseases "Sotiria"
Athens, 11527, Greece
University General Hospital of Heraklion
Crete, 71201, Greece
University of Patras Medical School
Pátrai, 26504, Greece
Euromedica Kyanous Stavros General Hospital
Thessaloniki, 54645, Greece
Health Center of Thermi, Thessaloniki
Thessaloniki, 57001, Greece
Interbalkan Medical Center of Thessaloniki
Thessaloniki, 57001, Greece
National Koranyi TBC and Pulm. Internal Med. Clinic
Budapest, 1121, Hungary
Semmelweis University
Budapest, 1125, Hungary
Pulmonology Institute of Veszprem County, Farkasgyepu
Farkasgyepű, 8582, Hungary
Jasz-Nagykun-Szolnok Megyei Hetenyi G. Korhaz-Rendelointezet
Szolnok, 5000, Hungary
Markusovszky University Teaching Hospital
Szombathely, 9700, Hungary
Tudogyogyintezet Torokbalint
Törökbálint, 2045, Hungary
ASST di Cremona
Cremona, 26100, Italy
Osp. Umberto I
Lugo (RA), 48022, Italy
Istituto Scientifico Romagnolo
Meldola (FC), 47014, Italy
Azienda Ospedaliera Universitaria Pisana
Pisa, 56124, Italy
Aichi Medical University Hospital
Aichi, Nagakute, 480-1195, Japan
Aichi Cancer Center Aichi Hospital
Aichi, Okazaki, 444-0011, Japan
Tosei General Hospital
Aichi, Seto, 489-8642, Japan
Fujita Health University Hospital
Aichi, Toyoake, 470-1192, Japan
Aso Co.,Ltd Iizuka Hospital
Fukuoka, Iizuka, 820-8505, Japan
Gunma Prefectural Cancer Center
Gunma, Ota, 373-8550, Japan
Hyogo Prefectural Amagasaki General Medical Center
Hyogo, Amagasaki, 660-8550, Japan
Itami City Hospital
Hyogo, Itami, 664-8540, Japan
Kobe City Medical Center General Hospital
Hyogo, Kobe, 650-0047, Japan
Ibaraki Prefectural Central Hospital
Ibaraki, Kasama, 309-1793, Japan
Kagawa Rosai Hospital
Kagawa, Marugame, 763-8502, Japan
Kitasato University Hospital
Kanagawa, Sagamihara, 252-0375, Japan
Yokohama City University Hospital
Kanagawa, Yokohama, 236-0004, Japan
Uji-Tokushukai Medical Center
Kyoto, Uji, 611-0041, Japan
Matsusaka City Hospital
Mie, Matsusaka, 515-8544, Japan
Miyazaki Prefectural Miyazaki Hospital
Miyazaki, Miyazaki, 880-8510, Japan
Nara Hospital Kinki University Faculty of Medicine
Nara, Ikoma, 630-0293, Japan
Niigata Cancer Center Hospital
Niigata, Niigata, 951-8566, Japan
Kansai Medical University Hospital
Osaka, Hirakata, 573-1191, Japan
Osaka Medical Center for Cancer and Cardiovascular Diseases
Osaka, Osaka, 537-8511, Japan
Takatsuki Red Cross Hospital
Osaka, Takatsuki, 569-1096, Japan
Saitama Medical University International Medical Center
Saitama, Hidaka, 350-1298, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
Sakaishi, 591-8555, Japan
Nippon Medical School Hospital
Tokyo, Bunkyo-ku, 113-8603, Japan
Nihon University Itabashi Hospital
Tokyo, Itabashi-ku, 173-8610, Japan
Japan Anti-Tuberculosis Association Fukujuji Hospital
Tokyo, Kiyose, 204-8522, Japan
Toranomon Hospital
Tokyo, Minato-ku, 105-8470, Japan
Hospital Pulau Pinang
Georgetown Pulau Pinang, 10990, Malaysia
University Malaya Medical Centre
Kuala Lumpur, 59100, Malaysia
Hospital Tengku Ampuan Afzan
Kuantan, 25100, Malaysia
Investigacion Biomedica para el Desarrollo de Farmacos
El Salto, 45680, Mexico
Unidad de Atencion Medica e Investigacion en Salud S.C.
Mérida, 97000, Mexico
Axis Heilsa S. de R.L. de C.V., Monterrey
Monterrey, 64060, Mexico
Clinical Medical Research S.C
Orizaba, 94300, Mexico
Hospital San Jose Querétaro
Querétaro, 76090, Mexico
Centro Hemato Oncológico Privado
Toluca, 50080, Mexico
Dr. Pablo O. Torre Memorial Hospital
Bacolod City, 6100, Philippines
Cebu Doctors Hospital
Cebu City, 6000, Philippines
Perpetual Succour Hospital (Cebu)
Cebu City, 6000, Philippines
Manila Doctors Hospital
Manila, 1000, Philippines
Lung Center of the Philippines
Quezon City, 1100, Philippines
Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej
Jelenia Góra, 58-506, Poland
KO-MED Centra Kliniczne Lublin II
Lublin, 20-362, Poland
Zofia Tarnowska domo Zamoyska,RegHosp.Cardiol.Dep,Tarnobrzeg
Tarnobrzeg, 39-400, Poland
The Provincial Polyclinical Hospital in Torun
Torun, 87-100, Poland
Onco.Cent. - Instit. of Maria Sklodowskiej-Curie
Warsaw, 02-781, Poland
Magodent Sp. Z o.o.
Warsaw, 04-125, Poland
CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
Coimbra, 3041-801, Portugal
Centro Hospitalar Lisboa Norte Hospital Pulido Valente
Lisbon, 1769-001, Portugal
IPO Porto Francisco Gentil, EPE
Porto, 4200-072, Portugal
Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião
Santa Maria da Feira, 4520-211, Portugal
Centro Hospitalar de Vila Nova de Gaia
Vila Nova de Gaia, 4434-502, Portugal
Baia Mare Emergency County Hospital
Baia Mare, 430031, Romania
Institute of Oncology 'Prof. Dr. Alexandru Trestioreanu'
Bucharest, 022328, Romania
Spitalul Militar de Urgenta Dr.Papilian, Cluj-Napoca
Cluj-Napoca, 400132, Romania
Spitalul Clinic Judetean de Urgenta Cluj Napoca
Cluj-Napoca, 400349, Romania
S.C Oncocenter Oncologie Clinica S.R.L
Timișoara, 300210, Romania
SBIH of Arkhangelsk reg. "Arkhangelsk Clin. Onc. Dispensary"
Arkhangelsk, 163045, Russia
St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"
Kazan', 420029, Russia
RBIH "Kursk regional clinical oncology dispensary"
Kursk, 305035, Russia
FSBI "N.N Blokhin Med.Res.Cent.Onc."MoH of RF
Moscow, 115478, Russia
BHI of Omsk region - Clinical Oncology Dispensary
Omsk, 644013, Russia
SBIH of Stavropol territory "Pyatigorsk Oncol. Dispensary"
Pyatigorsk, 357502, Russia
GUZ Leningradskaya Regional Clin. Hospital, St. Petersburg
Saint Petersburg, 194291, Russia
1stPavlov St.Med.Univ.St.-Petersburg Res.Inst.
Saint Petersburg, 197022, Russia
SPb SBIH "City Clinical Oncological Dispensary"
Saint Petersburg, 197022, Russia
FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF
Saint Petersburg, 197758, Russia
Institute for Oncol & Radiol of Serbia, Clinic f. Med. Onco.
Belgrade, 11000, Serbia
Clinical Center Bezanijska kosa, Belgrade
Belgrade, 11080, Serbia
Clinic of Pulmonary Diseases and Tuberculosis 'Knez Selo'
Gornji Matejevac, 18204, Serbia
Inst. for Pulm. Diseases of Vojvodine, Clinic f. Pulm. Oncol
Kamenitz, 21204, Serbia
Clinical Center Kragujevac
Kragujevac, 34000, Serbia
GVI Cape Gate Oncology Centre
Cape Town, 7570, South Africa
Rondebosch Oncology Centre
Cape Town, 7700, South Africa
GVI Oncology Outeniqua Unit
George, 6530, South Africa
West Rand Oncology Centre, Johannesburg
Johannesburg, 1709, South Africa
Langenhoven Drive Oncology Centre
Port Elizabeth, 6045, South Africa
Chungbuk National University Hospital
Cheongju-si, 361-711, South Korea
Chonnam National University Hwasun Hospital
Hwasun-gun, 519-763, South Korea
Gachon University Gil Medical Center
Incheon, 21565, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Korea University Guro Hospital
Seoul, 08308, South Korea
The Catholic University of Korea, St.Vincent's Hospital
Suwon, 16247, South Korea
Hospital Infanta Cristina
Badajoz, 06007, Spain
Hospital General Universitario Gregorio Marañón
Madrid, 28007, Spain
Hospital La Paz
Madrid, 28046, Spain
Hospital Clínico de Santiago
Santiago de Compostela, 15706, Spain
Hospital Virgen del Rocío
Seville, 41013, Spain
Hospital Nuestra Señora de Valme
Seville, 41014, Spain
Instituto Valenciano de Oncología
Valencia, 46009, Spain
Hospital Miguel Servet
Zaragoza, 50009, Spain
Songklanagarind Hospital
Hat Yai, 90110, Thailand
Ubonratchathani Cancer Hospital, Muang
Muang, 34000, Thailand
Udonthani Cancer Hospital, Muang
Muang, 41330, Thailand
Maharaj Nakorn Chiang Mai Hospital
Muang, 50200, Thailand
Lampang Hospital
Muang, 52000, Thailand
Naresuan University Hospital
Muang, 65000, Thailand
Akdeniz University Medical Faculty
Antalya, 7058, Turkey (Türkiye)
Inonu Uni. Med. Fac., Battalgazi
Battalgazi, 44280, Turkey (Türkiye)
Dicle University Medical Faculty
Diyarbakır, 21080, Turkey (Türkiye)
Trakya Universitesi Tip Fakultesi
Edirne, 22030, Turkey (Türkiye)
Gaziantep University
Gaziantep, 27310, Turkey (Türkiye)
Bezmi Alem Foundation University Medical Faculty Hospital
Istanbul, 34093, Turkey (Türkiye)
Yeditepe University Medical School Hospital
Istanbul, 34752, Turkey (Türkiye)
Fatih University Faculty of Medicince, Istanbul
Istanbul, 34844, Turkey (Türkiye)
CTPI Chernihiv Regional Oncological Dispensary, Chernihiv
Chernihiv, 14029, Ukraine
Munic.Instit."City Clin.Hosp.#4" of Dnipro City Council
Dnipropetrovsk, 49102, Ukraine
CHI Kharkiv Regional Clinical Oncological Center
Kharkiv, 61070, Ukraine
Kherson Regional Oncologic Dispensary, Kherson
Kherson, 73000, Ukraine
Treatment-Diagnostic CTR of Private Enterprise, Kirovohrad
Kirovohrad, 25006, Ukraine
CI Kryvyi Rih Oncological Dispensary of DRC
Kryvyi Rih, Dnipropetrovsk, 50048, Ukraine
National Institute of Cancer
Kyiv, 03022, Ukraine
Medical and Preventive Treatment Inst. Volyn Regional, Lutsk
Lutsk, 43018, Ukraine
CI of LRC Lviv Onco.Reg.Treat.&Diag.Cent.
Lviv, 79031, Ukraine
Poltava Regional Clinical Oncological Dispensary, Poltava
Poltava, 38011, Ukraine
Sumy Regional Oncology Center
Sumy, 40005, Ukraine
CI of TRC Ternopil RC Oncological Dispensary Thoracic Dept
Ternopil, 46023, Ukraine
Uzhgorod National University, Oncology Centre
Uzhhorod, 88000, Ukraine
Transcarpathian Reg Clin Oncological Dispensary, Uzhgorod
Uzhhorod, 88014, Ukraine
Vinnytsia Regional Clinical Oncological Dispensary
Vinnytsia, 21029, Ukraine
CI Zapor Reg Cl Oncological Dispensary of ZRC, Zhaporizhzhia
Zhaporizhzhia, 69040, Ukraine
Cheltenham General Hospital
Cheltenham, GL53 7AN, United Kingdom
Wythenshawe Hospital
Manchester, M23 9LT, United Kingdom
Can Tho Oncology Hospital
Can Tho, 000000, Vietnam
Bach Mai hospital
Hanoi, 100000, Vietnam
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
From 21 December 2017, after Week 18 primary analysis data cut-off, the Sponsor recommended to switch patients from BI 695502/US-licensed Avastin® to Avastin®. The main analyses to report all endpoint and AE results was the pre-switch period.
Results Point of Contact
- Title
- Boehringer Ingelheim, Call Centre
- Organization
- Boehringer Ingelheim
Study Officials
- STUDY CHAIR
Boehringer Ingelheim
Boehringer Ingelheim
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 21, 2014
First Posted
October 23, 2014
Study Start
July 8, 2015
Primary Completion
June 30, 2017
Study Completion
November 16, 2018
Last Updated
January 13, 2020
Results First Posted
January 13, 2020
Record last verified: 2019-12