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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02272413
Other study ID # 1302.5
Secondary ID 2014-002161-30
Status Completed
Phase Phase 3
First received
Last updated
Start date July 8, 2015
Est. completion date November 16, 2018

Study information

Verified date December 2019
Source Boehringer Ingelheim
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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®.


Recruitment information / eligibility

Status Completed
Enrollment 671
Est. completion date November 16, 2018
Est. primary completion date June 30, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion criteria:

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 + AvastinĀ®.

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:

Life expectancy > 6 months based on clinical judgment. Further inclusion criteria apply.

Exclusion criteria:

Prior therapy with monoclonal antibodies or small molecule inhibitors against Vascular Endothelial Growth Factor (VEGF) or VEGF receptors, including AvastinĀ®.

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).

History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding. Thrombotic or hemorrhagic event =< 6 months prior to Screening. Further exclusion criteria apply.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
BI 695502

Avastin


Locations

Country Name City State
Argentina CENIT - Centro de Neurociencias, Investigacion y Tratamiento Ciudad Autonoma Buenos Aires
Argentina Centro Oncológico de Rosario Rosario
Argentina Sanatorio Delta Rosario
Argentina Sanatorio Parque Rosario
Brazil CPCO - Centro de Pesquisa Clinica em Oncologia Cachoeiro de Itapemirim
Brazil Hospital do Cancer do Ceara Fortaleza
Brazil Pronutrir Fortaleza
Brazil Hospital de Carida de de Ijui - CACON Ijuí
Brazil Hospital Bruno Born Lajeado
Brazil Hospital da Cidade de Passo Fundo Passo Fundo
Brazil Universidade de Caxias do Sul - IPCEM - Inst. de Pesq.clilni Petrópolis
Brazil Hospital de Clínicas de Porto Alegre Porto Alegre
Brazil Irmandade da Santa Casa de Misericórdia de Porto Alegre Porto Alegre
Brazil CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia Santo André
Brazil ICAVC - Instituto do Cancer Arnaldo Vieira de Carvalho São Paulo
Brazil ICESP - Instituto do Cancer do Estado de Sao Paulo São Paulo
Brazil Clinica de Oncologia de Sorocaba Sorocaba
Bulgaria MHAT - Dobrich, AD Dobrich
Bulgaria UMHAT Georgi Stranski, Clinic of Paediatrics, Pleven Pleven
Bulgaria Complex Oncological Center - Plovdiv, EOOD Plovdiv
Bulgaria DCC 1 - Ruse, EOOD Ruse
Bulgaria MHAT 'Tokuda Hospital Sofia', EAD Sofia
Bulgaria MHAT Serdika, EOOD, Sofia Sofia
Bulgaria SHATOD 'Dr. Marko Antonov Markov'-Varna, EOOD Varna
Chile Centro Internacional de Estudios Clinicos - CIEC Santiago
Chile Clínica Santa María Santiago
Chile Hospital Clínico San Borja Arriarán Santiago
Chile Instituto Clínico Oncológico del Sur - ICOS Temuco
Chile Hospital Clinico Viña del Mar Viña del Mar
Croatia General Hospital Pula Pula
Croatia Clinical Hospital Centar Sestre Milosrdnice Zagreb
Croatia University Clinic for Pulmonary Diseases Zagreb
Egypt Alexandria University Hospital Alexandria
Egypt Ain Shams University Hospital Cairo
Egypt Nasser Institute Cairo
Egypt National Cancer Institute, Cairo University Cairo
Egypt Oncology Centre- Mansoura University Mansoura
Egypt Menofiya University Hospital Monofia
Germany Gesundheitszentrum Wetterau gGmbH Bad Nauheim
Greece Athens Hospital of Chest Diseases "Sotiria" Athens
Greece University General Hospital of Heraklion Crete
Greece University of Patras Medical School Patras
Greece Euromedica Kyanous Stavros General Hospital Thessaloniki
Greece Health Center of Thermi, Thessaloniki Thessaloniki
Greece Interbalkan Medical Center of Thessaloniki Thessaloniki
Hungary National Koranyi TBC and Pulm. Internal Med. Clinic Budapest
Hungary Semmelweis University Budapest
Hungary Pulmonology Institute of Veszprem County, Farkasgyepu Farkasgyepu
Hungary Jasz-Nagykun-Szolnok Megyei Hetenyi G. Korhaz-Rendelointezet Szolnok
Hungary Markusovszky University Teaching Hospital Szombathely
Hungary Tudogyogyintezet Torokbalint Torokbalint
Italy ASST di Cremona Cremona
Italy Osp. Umberto I Lugo (RA)
Italy Istituto Scientifico Romagnolo Meldola (FC)
Italy Azienda Ospedaliera Universitaria Pisana Pisa
Japan Aichi Medical University Hospital Aichi, Nagakute
Japan Aichi Cancer Center Aichi Hospital Aichi, Okazaki
Japan Tosei General Hospital Aichi, Seto
Japan Fujita Health University Hospital Aichi, Toyoake
Japan Aso Co.,Ltd Iizuka Hospital Fukuoka, Iizuka
Japan Gunma Prefectural Cancer Center Gunma, Ota
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 Ibaraki Prefectural Central Hospital Ibaraki, Kasama
Japan Kagawa Rosai Hospital Kagawa, Marugame
Japan Kitasato University Hospital Kanagawa, Sagamihara
Japan Yokohama City University Hospital Kanagawa, Yokohama
Japan Uji-Tokushukai Medical Center Kyoto, Uji
Japan Matsusaka City Hospital Mie, Matsusaka
Japan Miyazaki Prefectural Miyazaki Hospital Miyazaki, Miyazaki
Japan Nara Hospital Kinki University Faculty of Medicine Nara, Ikoma
Japan Niigata Cancer Center Hospital Niigata, Niigata
Japan Kansai Medical University Hospital Osaka, Hirakata
Japan Osaka Medical Center for Cancer and Cardiovascular Diseases Osaka, Osaka
Japan Takatsuki Red Cross Hospital Osaka, Takatsuki
Japan Saitama Medical University International Medical Center Saitama, Hidaka
Japan National Hospital Organization Kinki-Chuo Chest Medical Center Sakai-shi
Japan Nippon Medical School Hospital Tokyo, Bunkyo-ku
Japan Nihon University Itabashi Hospital Tokyo, Itabashi-ku
Japan Japan Anti-Tuberculosis Association Fukujuji Hospital Tokyo, Kiyose
Japan Toranomon Hospital Tokyo, Minato-ku
Korea, Republic of Chungbuk National University Hospital Cheongju-si
Korea, Republic of Chonnam National University Hwasun Hospital Hwasun-gun
Korea, Republic of Gachon University Gil Medical Center Incheon
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Korea University Guro Hospital Seoul
Korea, Republic of The Catholic University of Korea, St.Vincent's Hospital Suwon-si
Malaysia Hospital Pulau Pinang Georgetown Pulau Pinang
Malaysia University Malaya Medical Centre Kuala Lumpur
Malaysia Hospital Tengku Ampuan Afzan Kuantan
Mexico Investigacion Biomedica para el Desarrollo de Farmacos El Salto
Mexico Unidad de Atencion Medica e Investigacion en Salud S.C. Merida
Mexico Axis Heilsa S. de R.L. de C.V., Monterrey Monterrey
Mexico Clinical Medical Research S.C Orizaba
Mexico Hospital San Jose Querétaro Queretaro
Mexico Centro Hemato Oncológico Privado Toluca
Philippines Dr. Pablo O. Torre Memorial Hospital Bacolod City
Philippines Cebu Doctors Hospital Cebu City
Philippines Perpetual Succour Hospital (Cebu) Cebu City
Philippines Manila Doctors Hospital Manila
Philippines Lung Center of the Philippines Quezon City
Poland Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej Jelenia Gora
Poland 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 Magodent Sp. Z o.o. Warszawa
Poland Onco.Cent. - Instit. of Maria Sklodowskiej-Curie Warszawa
Portugal 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 Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião Santa Maria da Feira
Portugal Centro Hospitalar de Vila Nova de Gaia Vila Nova de Gaia
Romania Baia Mare Emergency County Hospital Baia Mare
Romania Institute of Oncology 'Prof. Dr. Alexandru Trestioreanu' Bucuresti
Romania Spitalul Clinic Judetean de Urgenta Cluj Napoca Cluj Napoca
Romania Spitalul Militar de Urgenta Dr.Papilian, Cluj-Napoca Cluj-Napoca
Romania S.C Oncocenter Oncologie Clinica S.R.L Timisoara
Russian Federation SBIH of Arkhangelsk reg. "Arkhangelsk Clin. Onc. Dispensary" Arkhangelsk
Russian Federation St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan" Kazan
Russian Federation RBIH "Kursk regional clinical oncology dispensary" Kursk
Russian Federation FSBI "N.N Blokhin Med.Res.Cent.Onc."MoH of RF Moscow
Russian Federation BHI of Omsk region - Clinical Oncology Dispensary Omsk
Russian Federation SBIH of Stavropol territory "Pyatigorsk Oncol. Dispensary" Pyatigorsk
Russian Federation 1stPavlov St.Med.Univ.St.-Petersburg Res.Inst. St. Petersburg
Russian Federation FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF St. Petersburg
Russian Federation GUZ Leningradskaya Regional Clin. Hospital, St. Petersburg St. Petersburg
Russian Federation SPb SBIH "City Clinical Oncological Dispensary" St. Petersburg
Serbia Clinical Center Bezanijska kosa, Belgrade Belgrade
Serbia Institute for Oncol & Radiol of Serbia, Clinic f. Med. Onco. Belgrade
Serbia Clinic of Pulmonary Diseases and Tuberculosis 'Knez Selo' Gornji Matejevac
Serbia Clinical Center Kragujevac Kragujevac
Serbia Inst. for Pulm. Diseases of Vojvodine, Clinic f. Pulm. Oncol Sremska Kamenica
South Africa GVI Cape Gate Oncology Centre Cape Town
South Africa Rondebosch Oncology Centre Cape town
South Africa GVI Oncology Outeniqua Unit George
South Africa West Rand Oncology Centre, Johannesburg Johannesburg
South Africa Langenhoven Drive Oncology Centre Port Elizabeth
Spain Hospital Infanta Cristina Badajoz
Spain Hospital General Universitario Gregorio Marañón Madrid
Spain Hospital La Paz Madrid
Spain Hospital Clínico de Santiago Santiago de Compostela
Spain Hospital Nuestra Señora de Valme Sevilla
Spain Hospital Virgen del Rocío Sevilla
Spain Instituto Valenciano de Oncología Valencia
Spain Hospital Miguel Servet Zaragoza
Thailand Songklanagarind Hospital Hat Yai
Thailand Lampang Hospital Muang
Thailand Maharaj Nakorn Chiang Mai Hospital Muang
Thailand Naresuan University Hospital Muang
Thailand Ubonratchathani Cancer Hospital, Muang Muang
Thailand Udonthani Cancer Hospital, Muang Muang
Turkey Akdeniz University Medical Faculty Antalya
Turkey Inonu Uni. Med. Fac., Battalgazi Battalgazi
Turkey Dicle University Medical Faculty Diyarbakir
Turkey Trakya Universitesi Tip Fakultesi Edirne
Turkey Gaziantep University Gaziantep
Turkey Bezmi Alem Foundation University Medical Faculty Hospital Istanbul
Turkey Fatih University Faculty of Medicince, Istanbul Istanbul
Turkey Yeditepe University Medical School Hospital Istanbul
Ukraine CTPI Chernihiv Regional Oncological Dispensary, Chernihiv Chernihiv
Ukraine Munic.Instit."City Clin.Hosp.#4" of Dnipro City Council Dnipropetrovsk
Ukraine CHI Kharkiv Regional Clinical Oncological Center Kharkiv
Ukraine Kherson Regional Oncologic Dispensary, Kherson Kherson
Ukraine Treatment-Diagnostic CTR of Private Enterprise, Kirovohrad Kirovohrad
Ukraine CI Kryvyi Rih Oncological Dispensary of DRC Kryvyi Rih, Dnipropetrovsk
Ukraine 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 Poltava Regional Clinical Oncological Dispensary, Poltava Poltava
Ukraine Sumy Regional Oncology Center Sumy
Ukraine CI of TRC Ternopil RC Oncological Dispensary Thoracic Dept Ternopil
Ukraine Transcarpathian Reg Clin Oncological Dispensary, Uzhgorod Uzhgorod
Ukraine Uzhgorod National University, Oncology Centre Uzhgorod
Ukraine Vinnytsia Regional Clinical Oncological Dispensary Vinnytsia
Ukraine CI Zapor Reg Cl Oncological Dispensary of ZRC, Zhaporizhzhia Zhaporizhzhia
United Kingdom Cheltenham General Hospital Cheltenham
United Kingdom Wythenshawe Hospital Manchester
United States Pacific Cancer Medical Center, Inc. Anaheim California
United States Ashland Bellefonte Cancer Center Ashland Kentucky
United States Comprehensive Blood and Cancer Center Bakersfield California
United States Carolinas Cancer Care Charlotte North Carolina
United States Lalita Pandit, M.D., Inc. Fountain Valley California
United States Southern California Oncology Research Alliance Los Angeles California
United States Detroit Clinical Research Center Owosso Michigan
United States Innovative Clinical Research, Inc. Whittier California
United States Reliant Medical Group Worcester Massachusetts
Vietnam Can Tho Oncology Hospital Can Tho
Vietnam Bach Mai hospital Hanoi

Sponsors (1)

Lead Sponsor Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Brazil,  Bulgaria,  Chile,  Croatia,  Egypt,  Germany,  Greece,  Hungary,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Mexico,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Serbia,  South Africa,  Spain,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Percentage of Patients With Selected Treatment-Emergent Adverse Events (TEAEs) For Comparability Assessment of BI 695502 and US-licensed Avastin® The following selected adverse events (AEs) were evaluated for comparability assessment of BI 695502 and US-licensed AvastinĀ®:
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.
From first dose of trial drug until 16 weeks after the last dose of trial medication, up to 218 days.
Secondary Progression-Free Survival (PFS) Time as Determined by Investigator Assessment 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. 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).
Secondary Overall Survival (OS) Time 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. From baseline until death due to any cause, ie., up to 35 cycles (105 weeks).
Secondary Duration of Response (DOR) as Determined by Investigator Assessment 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. 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).
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