Clinical trial NCT02272413: Phase III Trial BI 695502 Plus Chemotherapy vs. Avastin® Plus Chemotherapy in Patients With Lung Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-23
Enrollment: 671
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 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®.


Eligibility criteria: 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.

Primary outcomes:
measure: Best Overall Response Rate (ORR), Based on Unconfirmed Response Assessment, as Assessed by Central Imaging Review Until 18 Weeks After the Start of Treatment
timeFrame: 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:
measure: Percentage of Patients With Selected Treatment-Emergent Adverse Events (TEAEs) For Comparability Assessment of BI 695502 and US-licensed Avastin®
timeFrame: From first dose of trial drug until 16 weeks after the last dose of trial medication, up to 218 days.
measure: Progression-Free Survival (PFS) Time as Determined by Investigator Assessment
timeFrame: 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).
measure: Overall Survival (OS) Time
timeFrame: From baseline until death due to any cause, ie., up to 35 cycles (105 weeks).
measure: Duration of Response (DOR) as Determined by Investigator Assessment
timeFrame: 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).
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center, Inc.
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Fountain Valley
country: United States
facility: Lalita Pandit, M.D., Inc.
state: California
city: Los Angeles
country: United States
facility: Southern California Oncology Research Alliance
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research, Inc.
state: California
city: Ashland
country: United States
facility: Ashland Bellefonte Cancer Center
state: Kentucky
city: Worcester
country: United States
facility: Reliant Medical Group
state: Massachusetts
city: Owosso
country: United States
facility: Detroit Clinical Research Center
state: Michigan
city: Charlotte
country: United States
facility: Carolinas Cancer Care
state: North Carolina
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: CENIT - Centro de Neurociencias, Investigacion y Tratamiento
city: Rosario
country: Argentina
facility: Sanatorio Delta
city: Rosario
country: Argentina
facility: Sanatorio Parque
city: Rosario
country: Argentina
facility: Centro Oncológico de Rosario
city: Cachoeiro de Itapemirim
country: Brazil
facility: CPCO - Centro de Pesquisa Clinica em Oncologia
city: Fortaleza
country: Brazil
facility: Hospital do Cancer do Ceara
city: Fortaleza
country: Brazil
facility: Pronutrir
city: Ijuí
country: Brazil
facility: Hospital de Carida de de Ijui - CACON
city: Lajeado
country: Brazil
facility: Hospital Bruno Born
city: Passo Fundo
country: Brazil
facility: Hospital da Cidade de Passo Fundo
city: Petrópolis
country: Brazil
facility: Universidade de Caxias do Sul - IPCEM - Inst. de Pesq.clilni
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
city: Santo André
country: Brazil
facility: CEPHO - Centro de Estudos e Pesquisas em Hematologia e Oncologia
city: Sorocaba
country: Brazil
facility: Clinica de Oncologia de Sorocaba
city: São Paulo
country: Brazil
facility: ICAVC - Instituto do Cancer Arnaldo Vieira de Carvalho
city: São Paulo
country: Brazil
facility: ICESP - Instituto do Cancer do Estado de Sao Paulo
city: Dobrich
country: Bulgaria
facility: MHAT - Dobrich, AD
city: Pleven
country: Bulgaria
facility: UMHAT Georgi Stranski, Clinic of Paediatrics, Pleven
city: Plovdiv
country: Bulgaria
facility: Complex Oncological Center - Plovdiv, EOOD
city: Ruse
country: Bulgaria
facility: DCC 1 - Ruse, EOOD
city: Sofia
country: Bulgaria
facility: MHAT Serdika, EOOD, Sofia
city: Sofia
country: Bulgaria
facility: MHAT 'Tokuda Hospital Sofia', EAD
city: Varna
country: Bulgaria
facility: SHATOD 'Dr. Marko Antonov Markov'-Varna, EOOD
city: Santiago
country: Chile
facility: Clínica Santa María
city: Santiago
country: Chile
facility: Hospital Clínico San Borja Arriarán
city: Santiago
country: Chile
facility: Centro Internacional de Estudios Clinicos - CIEC
city: Temuco
country: Chile
facility: Instituto Clínico Oncológico del Sur - ICOS
city: Viña del Mar
country: Chile
facility: Hospital Clinico Viña del Mar
city: Pula
country: Croatia
facility: General Hospital Pula
city: Zagreb
country: Croatia
facility: Clinical Hospital Centar Sestre Milosrdnice
city: Zagreb
country: Croatia
facility: University Clinic for Pulmonary Diseases
city: Alexandria
country: Egypt
facility: Alexandria University Hospital
city: Cairo
country: Egypt
facility: Ain Shams University Hospital
city: Cairo
country: Egypt
facility: National Cancer Institute, Cairo University
city: Cairo
country: Egypt
facility: Nasser Institute
city: Mansoura
country: Egypt
facility: Oncology Centre- Mansoura University
city: Monofia
country: Egypt
facility: Menofiya University Hospital
city: Bad Nauheim
country: Germany
facility: Gesundheitszentrum Wetterau gGmbH
city: Athens
country: Greece
facility: Athens Hospital of Chest Diseases "Sotiria"
city: Crete
country: Greece
facility: University General Hospital of Heraklion
city: Patras
country: Greece
facility: University of Patras Medical School
city: Thessaloniki
country: Greece
facility: Euromedica Kyanous Stavros General Hospital
city: Thessaloniki
country: Greece
facility: Health Center of Thermi, Thessaloniki
city: Thessaloniki
country: Greece
facility: Interbalkan Medical Center of Thessaloniki
city: Budapest
country: Hungary
facility: National Koranyi TBC and Pulm. Internal Med. Clinic
city: Budapest
country: Hungary
facility: Semmelweis University
city: Farkasgyepu
country: Hungary
facility: Pulmonology Institute of Veszprem County, Farkasgyepu
city: Szolnok
country: Hungary
facility: Jasz-Nagykun-Szolnok Megyei Hetenyi G. Korhaz-Rendelointezet
city: Szombathely
country: Hungary
facility: Markusovszky University Teaching Hospital
city: Torokbalint
country: Hungary
facility: Tudogyogyintezet Torokbalint
city: Cremona
country: Italy
facility: ASST di Cremona
city: Lugo (RA)
country: Italy
facility: Osp. Umberto I
city: Meldola (FC)
country: Italy
facility: Istituto Scientifico Romagnolo
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
city: Aichi, Nagakute
country: Japan
facility: Aichi Medical University Hospital
city: Aichi, Okazaki
country: Japan
facility: Aichi Cancer Center Aichi Hospital
city: Aichi, Seto
country: Japan
facility: Tosei General Hospital
city: Aichi, Toyoake
country: Japan
facility: Fujita Health University Hospital
city: Fukuoka, Iizuka
country: Japan
facility: Aso Co.,Ltd Iizuka Hospital
city: Gunma, Ota
country: Japan
facility: Gunma Prefectural Cancer Center
city: Hyogo, Amagasaki
country: Japan
facility: Hyogo Prefectural Amagasaki General Medical Center
city: Hyogo, Itami
country: Japan
facility: Itami City Hospital
city: Hyogo, Kobe
country: Japan
facility: Kobe City Medical Center General Hospital
city: Ibaraki, Kasama
country: Japan
facility: Ibaraki Prefectural Central Hospital
city: Kagawa, Marugame
country: Japan
facility: Kagawa Rosai Hospital
city: Kanagawa, Sagamihara
country: Japan
facility: Kitasato University Hospital
city: Kanagawa, Yokohama
country: Japan
facility: Yokohama City University Hospital
city: Kyoto, Uji
country: Japan
facility: Uji-Tokushukai Medical Center
city: Mie, Matsusaka
country: Japan
facility: Matsusaka City Hospital
city: Miyazaki, Miyazaki
country: Japan
facility: Miyazaki Prefectural Miyazaki Hospital
city: Nara, Ikoma
country: Japan
facility: Nara Hospital Kinki University Faculty of Medicine
city: Niigata, Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Osaka, Hirakata
country: Japan
facility: Kansai Medical University Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka Medical Center for Cancer and Cardiovascular Diseases
city: Osaka, Takatsuki
country: Japan
facility: Takatsuki Red Cross Hospital
city: Saitama, Hidaka
country: Japan
facility: Saitama Medical University International Medical Center
city: Sakai-shi
country: Japan
facility: National Hospital Organization Kinki-Chuo Chest Medical Center
city: Tokyo, Bunkyo-ku
country: Japan
facility: Nippon Medical School Hospital
city: Tokyo, Itabashi-ku
country: Japan
facility: Nihon University Itabashi Hospital
city: Tokyo, Kiyose
country: Japan
facility: Japan Anti-Tuberculosis Association Fukujuji Hospital
city: Tokyo, Minato-ku
country: Japan
facility: Toranomon Hospital
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Hwasun-gun
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Suwon-si
country: Korea, Republic of
facility: The Catholic University of Korea, St.Vincent's Hospital
city: Georgetown Pulau Pinang
country: Malaysia
facility: Hospital Pulau Pinang
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuantan
country: Malaysia
facility: Hospital Tengku Ampuan Afzan
city: El Salto
country: Mexico
facility: Investigacion Biomedica para el Desarrollo de Farmacos
city: Merida
country: Mexico
facility: Unidad de Atencion Medica e Investigacion en Salud S.C.
city: Monterrey
country: Mexico
facility: Axis Heilsa S. de R.L. de C.V., Monterrey
city: Orizaba
country: Mexico
facility: Clinical Medical Research S.C
city: Queretaro
country: Mexico
facility: Hospital San Jose Querétaro
city: Toluca
country: Mexico
facility: Centro Hemato Oncológico Privado
city: Bacolod City
country: Philippines
facility: Dr. Pablo O. Torre Memorial Hospital
city: Cebu City
country: Philippines
facility: Cebu Doctors Hospital
city: Cebu City
country: Philippines
facility: Perpetual Succour Hospital (Cebu)
city: Manila
country: Philippines
facility: Manila Doctors Hospital
city: Quezon City
country: Philippines
facility: Lung Center of the Philippines
city: Jelenia Gora
country: Poland
facility: Wojewodzkie Centrum Szpitalne Kotliny Jeleniogorskiej
city: Lublin
country: Poland
facility: KO-MED Centra Kliniczne Lublin II
city: Tarnobrzeg
country: Poland
facility: Zofia Tarnowska domo Zamoyska,RegHosp.Cardiol.Dep,Tarnobrzeg
city: Torun
country: Poland
facility: The Provincial Polyclinical Hospital in Torun
city: Warszawa
country: Poland
facility: Onco.Cent. - Instit. of Maria Sklodowskiej-Curie
city: Warszawa
country: Poland
facility: Magodent Sp. Z o.o.
city: Coimbra
country: Portugal
facility: CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
city: Lisboa
country: Portugal
facility: Centro Hospitalar Lisboa Norte Hospital Pulido Valente
city: Porto
country: Portugal
facility: IPO Porto Francisco Gentil, EPE
city: Santa Maria da Feira
country: Portugal
facility: Centro Hospitalar de Entre o Douro e Vouga, E.P.E. - Hospital de São Sebastião
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia
city: Baia Mare
country: Romania
facility: Baia Mare Emergency County Hospital
city: Bucuresti
country: Romania
facility: Institute of Oncology 'Prof. Dr. Alexandru Trestioreanu'
city: Cluj Napoca
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Cluj Napoca
city: Cluj-Napoca
country: Romania
facility: Spitalul Militar de Urgenta Dr.Papilian, Cluj-Napoca
city: Timisoara
country: Romania
facility: S.C Oncocenter Oncologie Clinica S.R.L
city: Arkhangelsk
country: Russian Federation
facility: SBIH of Arkhangelsk reg. "Arkhangelsk Clin. Onc. Dispensary"
city: Kazan
country: Russian Federation
facility: St.Auton.Heal.Inst."Rep.Clin.Onc.Disp.of MoH of Rep. Tatarstan"
city: Kursk
country: Russian Federation
facility: RBIH "Kursk regional clinical oncology dispensary"
city: Moscow
country: Russian Federation
facility: FSBI "N.N Blokhin Med.Res.Cent.Onc."MoH of RF
city: Omsk
country: Russian Federation
facility: BHI of Omsk region - Clinical Oncology Dispensary
city: Pyatigorsk
country: Russian Federation
facility: SBIH of Stavropol territory "Pyatigorsk Oncol. Dispensary"
city: St. Petersburg
country: Russian Federation
facility: GUZ Leningradskaya Regional Clin. Hospital, St. Petersburg
city: St. Petersburg
country: Russian Federation
facility: 1stPavlov St.Med.Univ.St.-Petersburg Res.Inst.
city: St. Petersburg
country: Russian Federation
facility: SPb SBIH "City Clinical Oncological Dispensary"
city: St. Petersburg
country: Russian Federation
facility: FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF
city: Belgrade
country: Serbia
facility: Institute for Oncol & Radiol of Serbia, Clinic f. Med. Onco.
city: Belgrade
country: Serbia
facility: Clinical Center Bezanijska kosa, Belgrade
city: Gornji Matejevac
country: Serbia
facility: Clinic of Pulmonary Diseases and Tuberculosis 'Knez Selo'
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: Sremska Kamenica
country: Serbia
facility: Inst. for Pulm. Diseases of Vojvodine, Clinic f. Pulm. Oncol
city: Cape Town
country: South Africa
facility: GVI Cape Gate Oncology Centre
city: Cape town
country: South Africa
facility: Rondebosch Oncology Centre
city: George
country: South Africa
facility: GVI Oncology Outeniqua Unit
city: Johannesburg
country: South Africa
facility: West Rand Oncology Centre, Johannesburg
city: Port Elizabeth
country: South Africa
facility: Langenhoven Drive Oncology Centre
city: Badajoz
country: Spain
facility: Hospital Infanta Cristina
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital La Paz
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico de Santiago
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Sevilla
country: Spain
facility: Hospital Nuestra Señora de Valme
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Zaragoza
country: Spain
facility: Hospital Miguel Servet
city: Hat Yai
country: Thailand
facility: Songklanagarind Hospital
city: Muang
country: Thailand
facility: Ubonratchathani Cancer Hospital, Muang
city: Muang
country: Thailand
facility: Udonthani Cancer Hospital, Muang
city: Muang
country: Thailand
facility: Maharaj Nakorn Chiang Mai Hospital
city: Muang
country: Thailand
facility: Lampang Hospital
city: Muang
country: Thailand
facility: Naresuan University Hospital
city: Antalya
country: Turkey
facility: Akdeniz University Medical Faculty
city: Battalgazi
country: Turkey
facility: Inonu Uni. Med. Fac., Battalgazi
city: Diyarbakir
country: Turkey
facility: Dicle University Medical Faculty
city: Edirne
country: Turkey
facility: Trakya Universitesi Tip Fakultesi
city: Gaziantep
country: Turkey
facility: Gaziantep University
city: Istanbul
country: Turkey
facility: Bezmi Alem Foundation University Medical Faculty Hospital
city: Istanbul
country: Turkey
facility: Yeditepe University Medical School Hospital
city: Istanbul
country: Turkey
facility: Fatih University Faculty of Medicince, Istanbul
city: Chernihiv
country: Ukraine
facility: CTPI Chernihiv Regional Oncological Dispensary, Chernihiv
city: Dnipropetrovsk
country: Ukraine
facility: Munic.Instit."City Clin.Hosp.#4" of Dnipro City Council
city: Kharkiv
country: Ukraine
facility: CHI Kharkiv Regional Clinical Oncological Center
city: Kherson
country: Ukraine
facility: Kherson Regional Oncologic Dispensary, Kherson
city: Kirovohrad
country: Ukraine
facility: Treatment-Diagnostic CTR of Private Enterprise, Kirovohrad
city: Kryvyi Rih, Dnipropetrovsk
country: Ukraine
facility: CI Kryvyi Rih Oncological Dispensary of DRC
city: Kyiv
country: Ukraine
facility: National Institute of Cancer
city: Lutsk
country: Ukraine
facility: Medical and Preventive Treatment Inst. Volyn Regional, Lutsk
city: Lviv
country: Ukraine
facility: CI of LRC Lviv Onco.Reg.Treat.&Diag.Cent.
city: Poltava
country: Ukraine
facility: Poltava Regional Clinical Oncological Dispensary, Poltava
city: Sumy
country: Ukraine
facility: Sumy Regional Oncology Center
city: Ternopil
country: Ukraine
facility: CI of TRC Ternopil RC Oncological Dispensary Thoracic Dept
city: Uzhgorod
country: Ukraine
facility: Uzhgorod National University, Oncology Centre
city: Uzhgorod
country: Ukraine
facility: Transcarpathian Reg Clin Oncological Dispensary, Uzhgorod
city: Vinnytsia
country: Ukraine
facility: Vinnytsia Regional Clinical Oncological Dispensary
city: Zhaporizhzhia
country: Ukraine
facility: CI Zapor Reg Cl Oncological Dispensary of ZRC, Zhaporizhzhia
city: Cheltenham
country: United Kingdom
facility: Cheltenham General Hospital
city: Manchester
country: United Kingdom
facility: Wythenshawe Hospital
city: Can Tho
country: Vietnam
facility: Can Tho Oncology Hospital
city: Hanoi
country: Vietnam
facility: Bach Mai hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: