Phase III Trial BI 695502 Plus Chemotherapy vs. Avastin® Plus Chemotherapy in Patients With Lung Cancer
- Registration Number
- NCT02272413
- Lead Sponsor
- Boehringer Ingelheim
- 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®.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 671
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BI 695502 BI 695502 - Avastin Avastin -
- Primary Outcome Measures
Name Time Method Best Overall Response Rate (ORR), Based on Unconfirmed Response Assessment, as Assessed by Central Imaging Review Until 18 Weeks After the Start of Treatment 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. 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.
- Secondary Outcome Measures
Name Time Method 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. The following selected adverse events (AEs) were evaluated for comparability assessment of BI 695502 and US-licensed Avastin®:
* Infusion reactions (anaphylactic/hypersensitivity/infusion-related reactions),
* Thromboembolic events (arterial or venous),
* Febrile neutropenia,
* Gastrointestinal perforations,
* Hypertension,
* Proteinuria,
* Pulmonary hemorrhage,
* Other hemorrhages (not including pulmonary hemorrhages),
* Wound-healing complications/abscess/fistulas. The analysis of AEs was based on the concept of TEAEs. For non-switched patients, all AEs that started or worsened in severity on or after the first dose of trial drug and prior to the date of last administration of trial medication + 16 weeks inclusive were defined as TEAEs.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). PFS was defined as the time from randomization until disease progression as determined by Investigator assessment or death from any cause, whichever occurred first during the pre-switch period. Disease progression was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 millimeters. Tumor assessments were performed prior to trial drug administration. PFS was calculated using the Kaplan-Meier technique.
Overall Survival (OS) Time From baseline until death due to any cause, ie., up to 35 cycles (105 weeks). OS was defined as the time randomization until death from any cause during the pre-switch period. OS was calculated using the Kaplan-Meier technique.
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). DOR was the time from first documented CR or PR until time of progression as determined by Investigator assessment during the pre-switch period. Tumor assessments were performed prior to trial drug administration. DOR was calculated using the Kaplan-Meier technique.
Trial Locations
- Locations (189)
Pacific Cancer Medical Center, Inc.
🇺🇸Anaheim, California, United States
Southern California Oncology Research Alliance
🇺🇸Los Angeles, California, United States
CI Zapor Reg Cl Oncological Dispensary of ZRC, Zhaporizhzhia
🇺🇦Zhaporizhzhia, Ukraine
Poltava Regional Clinical Oncological Dispensary, Poltava
🇺🇦Poltava, Ukraine
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Cebu Doctors Hospital
🇵🇭Cebu City, Philippines
Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião
🇵🇹Santa Maria da Feira, Portugal
Inst. for Pulm. Diseases of Vojvodine, Clinic f. Pulm. Oncol
🇷🇸Sremska Kamenica, Serbia
Perpetual Succour Hospital (Cebu)
🇵🇭Cebu City, Philippines
Clinic of Pulmonary Diseases and Tuberculosis 'Knez Selo'
🇷🇸Gornji Matejevac, Serbia
Maharaj Nakorn Chiang Mai Hospital
🇹🇭Muang, Thailand
Unidad de Atencion Medica e Investigacion en Salud S.C.
🇲🇽Merida, Mexico
Hospital San Jose Querétaro
🇲🇽Queretaro, Mexico
Dr. Pablo O. Torre Memorial Hospital
🇵🇭Bacolod City, Philippines
Clinical Center Bezanijska kosa, Belgrade
🇷🇸Belgrade, Serbia
Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Naresuan University Hospital
🇹🇭Muang, Thailand
Lampang Hospital
🇹🇭Muang, Thailand
Detroit Clinical Research Center
🇺🇸Owosso, Michigan, United States
CPCO - Centro de Pesquisa Clinica em Oncologia
🇧🇷Cachoeiro de Itapemirim, Brazil
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
Lalita Pandit, M.D., Inc.
🇺🇸Fountain Valley, California, United States
Hospital do Cancer do Ceara
🇧🇷Fortaleza, Brazil
Clínica Santa María
🇨🇱Santiago, Chile
Hospital Clinico Viña del Mar
🇨🇱Viña del Mar, Chile
CENIT - Centro de Neurociencias, Investigacion y Tratamiento
🇦🇷Ciudad Autonoma Buenos Aires, Argentina
Sanatorio Delta
🇦🇷Rosario, Argentina
MHAT 'Tokuda Hospital Sofia', EAD
🇧🇬Sofia, Bulgaria
Sanatorio Parque
🇦🇷Rosario, Argentina
Clinica de Oncologia de Sorocaba
🇧🇷Sorocaba, Brazil
ICESP - Instituto do Cancer do Estado de Sao Paulo
🇧🇷São Paulo, Brazil
UMHAT Georgi Stranski, Clinic of Paediatrics, Pleven
🇧🇬Pleven, Bulgaria
Irmandade da Santa Casa de Misericórdia de Porto Alegre
🇧🇷Porto Alegre, Brazil
Centro Oncológico de Rosario
🇦🇷Rosario, Argentina
Hospital de Carida de de Ijui - CACON
🇧🇷Ijuí, Brazil
CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
🇧🇷Santo André, Brazil
Centro Internacional de Estudios Clinicos - CIEC
🇨🇱Santiago, Chile
DCC 1 - Ruse, EOOD
🇧🇬Ruse, Bulgaria
MHAT Serdika, EOOD, Sofia
🇧🇬Sofia, Bulgaria
ICAVC - Instituto do Cancer Arnaldo Vieira de Carvalho
🇧🇷São Paulo, Brazil
Hospital Clínico San Borja Arriarán
🇨🇱Santiago, Chile
Instituto Clínico Oncológico del Sur - ICOS
🇨🇱Temuco, Chile
MHAT - Dobrich, AD
🇧🇬Dobrich, Bulgaria
SHATOD 'Dr. Marko Antonov Markov'-Varna, EOOD
🇧🇬Varna, Bulgaria
Clinical Hospital Centar Sestre Milosrdnice
🇭🇷Zagreb, Croatia
Nasser Institute
🇪🇬Cairo, Egypt
University of Patras Medical School
🇬🇷Patras, Greece
Ain Shams University Hospital
🇪🇬Cairo, Egypt
Alexandria University Hospital
🇪🇬Alexandria, Egypt
Oncology Centre- Mansoura University
🇪🇬Mansoura, Egypt
Menofiya University Hospital
🇪🇬Monofia, Egypt
Semmelweis University
🇭🇺Budapest, Hungary
Pulmonology Institute of Veszprem County, Farkasgyepu
🇭🇺Farkasgyepu, Hungary
Athens Hospital of Chest Diseases "Sotiria"
🇬🇷Athens, Greece
Markusovszky University Teaching Hospital
🇭🇺Szombathely, Hungary
Gesundheitszentrum Wetterau gGmbH
🇩🇪Bad Nauheim, Germany
University General Hospital of Heraklion
🇬🇷Crete, Greece
Osaka Medical Center for Cancer and Cardiovascular Diseases
🇯🇵Osaka, Osaka, Japan
Miyazaki Prefectural Miyazaki Hospital
🇯🇵Miyazaki, Miyazaki, Japan
Euromedica Kyanous Stavros General Hospital
🇬🇷Thessaloniki, Greece
Osp. Umberto I
🇮🇹Lugo (RA), Italy
Interbalkan Medical Center of Thessaloniki
🇬🇷Thessaloniki, Greece
Istituto Scientifico Romagnolo
🇮🇹Meldola (FC), Italy
Aichi Cancer Center Aichi Hospital
🇯🇵Aichi, Okazaki, Japan
Kansai Medical University Hospital
🇯🇵Osaka, Hirakata, Japan
Saitama Medical University International Medical Center
🇯🇵Saitama, Hidaka, Japan
Uji-Tokushukai Medical Center
🇯🇵Kyoto, Uji, Japan
Nara Hospital Kinki University Faculty of Medicine
🇯🇵Nara, Ikoma, Japan
Takatsuki Red Cross Hospital
🇯🇵Osaka, Takatsuki, Japan
Investigacion Biomedica para el Desarrollo de Farmacos
🇲🇽El Salto, Mexico
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Nippon Medical School Hospital
🇯🇵Tokyo, Bunkyo-ku, Japan
Japan Anti-Tuberculosis Association Fukujuji Hospital
🇯🇵Tokyo, Kiyose, Japan
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Malaysia
Manila Doctors Hospital
🇵🇭Manila, Philippines
Centro Hemato Oncológico Privado
🇲🇽Toluca, Mexico
Institute of Oncology 'Prof. Dr. Alexandru Trestioreanu'
🇷🇴Bucuresti, Romania
SBIH of Arkhangelsk reg. "Arkhangelsk Clin. Onc. Dispensary"
🇷🇺Arkhangelsk, Russian Federation
Baia Mare Emergency County Hospital
🇷🇴Baia Mare, Romania
FSBI "N.N Blokhin Med.Res.Cent.Onc."MoH of RF
🇷🇺Moscow, Russian Federation
GUZ Leningradskaya Regional Clin. Hospital, St. Petersburg
🇷🇺St. Petersburg, Russian Federation
Spitalul Clinic Judetean de Urgenta Cluj Napoca
🇷🇴Cluj Napoca, Romania
Hospital Virgen del Rocío
🇪🇸Sevilla, Spain
Institute for Oncol & Radiol of Serbia, Clinic f. Med. Onco.
🇷🇸Belgrade, Serbia
Rondebosch Oncology Centre
🇿🇦Cape town, South Africa
Ubonratchathani Cancer Hospital, Muang
🇹🇭Muang, Thailand
Akdeniz University Medical Faculty
🇹🇷Antalya, Turkey
National Institute of Cancer
🇺🇦Kyiv, Ukraine
Medical and Preventive Treatment Inst. Volyn Regional, Lutsk
🇺🇦Lutsk, Ukraine
CI of LRC Lviv Onco.Reg.Treat.&Diag.Cent.
🇺🇦Lviv, Ukraine
Sumy Regional Oncology Center
🇺🇦Sumy, Ukraine
Wythenshawe Hospital
🇬🇧Manchester, United Kingdom
Pronutrir
🇧🇷Fortaleza, Brazil
Universidade de Caxias do Sul - IPCEM - Inst. de Pesq.clilni
🇧🇷Petrópolis, Brazil
Innovative Clinical Research, Inc.
🇺🇸Whittier, California, United States
Hospital da Cidade de Passo Fundo
🇧🇷Passo Fundo, Brazil
Hospital de Clínicas de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hospital Bruno Born
🇧🇷Lajeado, Brazil
Complex Oncological Center - Plovdiv, EOOD
🇧🇬Plovdiv, Bulgaria
General Hospital Pula
🇭🇷Pula, Croatia
University Clinic for Pulmonary Diseases
🇭🇷Zagreb, Croatia
National Cancer Institute, Cairo University
🇪🇬Cairo, Egypt
National Koranyi TBC and Pulm. Internal Med. Clinic
🇭🇺Budapest, Hungary
Health Center of Thermi, Thessaloniki
🇬🇷Thessaloniki, Greece
Jasz-Nagykun-Szolnok Megyei Hetenyi G. Korhaz-Rendelointezet
🇭🇺Szolnok, Hungary
ASST di Cremona
🇮🇹Cremona, Italy
Tudogyogyintezet Torokbalint
🇭🇺Torokbalint, Hungary
Azienda Ospedaliera Universitaria Pisana
🇮🇹Pisa, Italy
Aichi Medical University Hospital
🇯🇵Aichi, Nagakute, Japan
Gunma Prefectural Cancer Center
🇯🇵Gunma, Ota, Japan
Tosei General Hospital
🇯🇵Aichi, Seto, Japan
Aso Co.,Ltd Iizuka Hospital
🇯🇵Fukuoka, Iizuka, Japan
Fujita Health University Hospital
🇯🇵Aichi, Toyoake, Japan
Hyogo Prefectural Amagasaki General Medical Center
🇯🇵Hyogo, Amagasaki, Japan
Itami City Hospital
🇯🇵Hyogo, Itami, Japan
Kobe City Medical Center General Hospital
🇯🇵Hyogo, Kobe, Japan
Kagawa Rosai Hospital
🇯🇵Kagawa, Marugame, Japan
Ibaraki Prefectural Central Hospital
🇯🇵Ibaraki, Kasama, Japan
Kitasato University Hospital
🇯🇵Kanagawa, Sagamihara, Japan
Yokohama City University Hospital
🇯🇵Kanagawa, Yokohama, Japan
Matsusaka City Hospital
🇯🇵Mie, Matsusaka, Japan
National Hospital Organization Kinki-Chuo Chest Medical Center
🇯🇵Sakai-shi, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Niigata, Japan
Toranomon Hospital
🇯🇵Tokyo, Minato-ku, Japan
Nihon University Itabashi Hospital
🇯🇵Tokyo, Itabashi-ku, Japan
Chonnam National University Hwasun Hospital
🇰🇷Hwasun-gun, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
The Catholic University of Korea, St.Vincent's Hospital
🇰🇷Suwon-si, Korea, Republic of
Hospital Pulau Pinang
🇲🇾Georgetown Pulau Pinang, Malaysia
Axis Heilsa S. de R.L. de C.V., Monterrey
🇲🇽Monterrey, Mexico
Clinical Medical Research S.C
🇲🇽Orizaba, Mexico
Lung Center of the Philippines
🇵🇭Quezon City, Philippines
KO-MED Centra Kliniczne Lublin II
🇵🇱Lublin, Poland
Zofia Tarnowska domo Zamoyska,RegHosp.Cardiol.Dep,Tarnobrzeg
🇵🇱Tarnobrzeg, Poland
The Provincial Polyclinical Hospital in Torun
🇵🇱Torun, Poland
Onco.Cent. - Instit. of Maria Sklodowskiej-Curie
🇵🇱Warszawa, Poland
CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
🇵🇹Coimbra, Portugal
Centro Hospitalar Lisboa Norte Hospital Pulido Valente
🇵🇹Lisboa, Portugal
IPO Porto Francisco Gentil, EPE
🇵🇹Porto, Portugal
Magodent Sp. Z o.o.
🇵🇱Warszawa, Poland
Centro Hospitalar de Vila Nova de Gaia
🇵🇹Vila Nova de Gaia, Portugal
Spitalul Militar de Urgenta Dr.Papilian, Cluj-Napoca
🇷🇴Cluj-Napoca, Romania
S.C Oncocenter Oncologie Clinica S.R.L
🇷🇴Timisoara, Romania
RBIH "Kursk regional clinical oncology dispensary"
🇷🇺Kursk, Russian Federation
St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"
🇷🇺Kazan, Russian Federation
BHI of Omsk region - Clinical Oncology Dispensary
🇷🇺Omsk, Russian Federation
1stPavlov St.Med.Univ.St.-Petersburg Res.Inst.
🇷🇺St. Petersburg, Russian Federation
SBIH of Stavropol territory "Pyatigorsk Oncol. Dispensary"
🇷🇺Pyatigorsk, Russian Federation
SPb SBIH "City Clinical Oncological Dispensary"
🇷🇺St. Petersburg, Russian Federation
FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF
🇷🇺St. Petersburg, Russian Federation
GVI Cape Gate Oncology Centre
🇿🇦Cape Town, South Africa
GVI Oncology Outeniqua Unit
🇿🇦George, South Africa
West Rand Oncology Centre, Johannesburg
🇿🇦Johannesburg, South Africa
Hospital Infanta Cristina
🇪🇸Badajoz, Spain
Udonthani Cancer Hospital, Muang
🇹🇭Muang, Thailand
Langenhoven Drive Oncology Centre
🇿🇦Port Elizabeth, South Africa
Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
Hospital La Paz
🇪🇸Madrid, Spain
Hospital Clínico de Santiago
🇪🇸Santiago de Compostela, Spain
Hospital Miguel Servet
🇪🇸Zaragoza, Spain
Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Hospital Nuestra Señora de Valme
🇪🇸Sevilla, Spain
Songklanagarind Hospital
🇹🇭Hat Yai, Thailand
Trakya Universitesi Tip Fakultesi
🇹🇷Edirne, Turkey
Inonu Uni. Med. Fac., Battalgazi
🇹🇷Battalgazi, Turkey
Bezmi Alem Foundation University Medical Faculty Hospital
🇹🇷Istanbul, Turkey
Dicle University Medical Faculty
🇹🇷Diyarbakir, Turkey
Gaziantep University
🇹🇷Gaziantep, Turkey
Yeditepe University Medical School Hospital
🇹🇷Istanbul, Turkey
CHI Kharkiv Regional Clinical Oncological Center
🇺🇦Kharkiv, Ukraine
CTPI Chernihiv Regional Oncological Dispensary, Chernihiv
🇺🇦Chernihiv, Ukraine
Fatih University Faculty of Medicince, Istanbul
🇹🇷Istanbul, Turkey
Treatment-Diagnostic CTR of Private Enterprise, Kirovohrad
🇺🇦Kirovohrad, Ukraine
Kherson Regional Oncologic Dispensary, Kherson
🇺🇦Kherson, Ukraine
CI Kryvyi Rih Oncological Dispensary of DRC
🇺🇦Kryvyi Rih, Dnipropetrovsk, Ukraine
Uzhgorod National University, Oncology Centre
🇺🇦Uzhgorod, Ukraine
CI of TRC Ternopil RC Oncological Dispensary Thoracic Dept
🇺🇦Ternopil, Ukraine
Cheltenham General Hospital
🇬🇧Cheltenham, United Kingdom
Can Tho Oncology Hospital
🇻🇳Can Tho, Vietnam
Bach Mai hospital
🇻🇳Hanoi, Vietnam
Ashland Bellefonte Cancer Center
🇺🇸Ashland, Kentucky, United States
Reliant Medical Group
🇺🇸Worcester, Massachusetts, United States
Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej
🇵🇱Jelenia Gora, Poland
Transcarpathian Reg Clin Oncological Dispensary, Uzhgorod
🇺🇦Uzhgorod, Ukraine
Munic.Instit."City Clin.Hosp.#4" of Dnipro City Council
🇺🇦Dnipropetrovsk, Ukraine
Vinnytsia Regional Clinical Oncological Dispensary
🇺🇦Vinnytsia, Ukraine
Carolinas Cancer Care
🇺🇸Charlotte, North Carolina, United States