Phase III Trial BI 695502 Plus Chemotherapy vs. Avastin® Plus Chemotherapy in Patients With Lung Cancer

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official title:

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

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
• 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
• 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 + 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:

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 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).

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

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 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.	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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