Clinical trial NCT03371017: A Study of the Efficacy and Safety of Atezolizumab Plus Chemotherapy for Patients With Early Relapsing Recurrent Triple-Negative Breast Cancer
Official title: A Phase III, Randomised, Double-Blind, Placebo-Controlled, Multicentre Study Of The Efficacy And Safety Of Atezolizumab Plus Chemotherapy For Patients With Early Relapsing Recurrent (Inoperable Locally Advanced Or Metastatic) Triple-Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Triple Negative Breast Neoplasms
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-12-13
Enrollment: 595
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: This study will evaluate the efficacy and safety of atezolizumab plus chemotherapy compared with placebo plus chemotherapy in patients with inoperable recurrent triple-negative breast cancer (TNBC).


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed triple negative breast cancer (TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic
* Documented disease progression occurring within 12 months from the last treatment with curative intent
* Prior treatment (of early breast cancer) with an anthracycline and taxane
* Have not received prior chemotherapy or targeted systemic therapy for their locally advanced inoperable or metastatic recurrence. Prior radiation therapy for recurrent disease is permitted
* Measurable or non-measurable disease, as defined by RECIST 1.1
* Availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumour block (preferred) or at least 17 unstained slides obtained from relapsed metastatic or locally advanced diseases may be submitted, if clinically feasible, with an associated pathology report, if available. If a fresh tumour sample is not clinically feasible, either the diagnosis sample, the primary surgical resection sample, or the most recent FFPE tumour biopsy sample should be used.
* Eastern Cooperative Oncology Group performance status 0-1
* Life expectancy ≥ 12 weeks
* Adequate haematologic and end-organ function
* Negative human immunodeficiency virus (HIV) test ---Negative hepatitis B surface antigen (HBsAg) test at screening
* Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
* The HBV DNA test will be performed only for patients who have a negative HBsAg and a positive HBcAb test.
* Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening.
* Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use a contraceptive method with a failure rate of ≤1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of capecitabine, whichever is later. In addition, women must refrain from donating eggs during the same time period.
* Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm

Inclusion criteria for patients enrolled after the recruitment of all-comers is complete:

-PD-L1-positive tumour status (assessed centrally prior to randomisation), defined as PD-L1 expression on tumour-infiltrating immune cells (IC) of 1% or greater.

Exclusion Criteria:

* Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \> 2 weeks prior to randomisation
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
* Symptomatic or rapid visceral progression
* No prior treatment with an anthracycline and taxane
* History of leptomeningeal disease
* Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently) (patients with indwelling catheters such as PleurX® are allowed)
* Uncontrolled tumour-related pain
* Uncontrolled or symptomatic hypercalcemia
* Malignancies other than TNBC within 5 years prior to randomisation)
* Significant cardiovascular disease, within 3 months prior to randomisation, unstable arrhythmias, or unstable angina
* Presence of an abnormal ECG
* Severe infection requiring oral or IV antibiotics within 4 weeks prior to randomisation, including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia.
* Current treatment with anti-viral therapy for HBV.
* Major surgical procedure within 4 weeks prior to randomisation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis
* Treatment with investigational therapy within 28 days prior to randomisation
* Pregnant or lactating, or intending to become pregnant during or within 5 months after the last dose of atezolizumab, or within 6 months after the last dose of capecitabine, whichever is later.

Exclusion Criteria Related to Atezolizumab:

* History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanised antibodies or fusion proteins
* Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or to any component of the atezolizumab formulation
* History of autoimmune disease
* Prior allogeneic stem cell or solid organ transplantation
* History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e. bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computerised tomography (CT) scan History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
* Active tuberculosis
* Receipt of a live, attenuated vaccine within 4 weeks prior to randomisation or anticipation that a live, attenuated vaccine will be required during atezolizumab/placebo treatment or within 5 months after the last dose of atezolizumab/placebo
* Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents
* Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin \[IL\]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to randomisation
* Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of study treatment, or anticipated requirement for systemic immunosuppressive medications during the trial

Exclusion Criteria Related to Capecitabine:

* Inability to swallow pills
* Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
* Known dihydropyrimidine dehydrogenase (DPD) deficiency or history of severe and unexpected reactions to fluoropyrimidine therapy in patients selected to receive capecitabine

Exclusion Criteria Related to Carboplatin/Gemcitabine:

-Hypersensitivity to platinum containing compounds or any component of carboplatin or gemcitabine drug formulations in patients selected to receive carboplatin and Gemcitabine

Primary outcomes:
measure: Overall Survival (OS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status
timeFrame: Baseline to end of study (approximately 58 months)
measure: Overall Survival (OS) in Modified Intent-To-Treat (mITT) Popluation
timeFrame: Baseline to end of study (approximately 58 months)
Secondary outcomes:
measure: Proportion of Participants Alive 12 Months
timeFrame: Randomization to 12 months post randomization
measure: Proportion of Participants Alive 18 Months
timeFrame: Randomization to 18 months post randomization
measure: Progression-Free Survival (PFS) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status
timeFrame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
measure: Progression-Free Survival (PFS) in mITT population
timeFrame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
measure: Objective Response Rate (ORR) in Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status
timeFrame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
measure: Objective Response Rate (ORR) in Modified Intent-To-Treat (mITT) Popluation
timeFrame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
measure: Duration of Objective Response (DoR)
timeFrame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
measure: Clinical Benefit Rate (CBR)
timeFrame: 8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 58 months)
measure: Confirmed Objective Response Rate (C-ORR)
timeFrame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
measure: Duration of Response for Confirmed Responders (C-DoR)
timeFrame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
measure: Time to Confirmed Deterioration (TTD) of GHS/QoL
timeFrame: Baseline to end of study (approximately 58 months)
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline to end of study (approximately 58 months)
measure: Maximum Serum Concentration (Cmax) of Atezolizumab
timeFrame: At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days)
measure: Minimum Serum Concentration (Cmin) of Atezolizumab
timeFrame: At pre-defined intervals from Day 1, Cycle 1 through Cycle 4 (cycle = 21 days)
measure: Incidence of Anti-Drug Antibodies (ADAs) to Atezolizumab
timeFrame: Baseline to end of study (approximately 58 months)
measure: Relationship Between PD-L1 Protein Expression in Screening Tumour Tissue and Clinical Outcomes
timeFrame: Baseline to end of study (approximately 58 months)
measure: Overall Survival (OS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status
timeFrame: Baseline to end of study (approximately 58 months)
measure: Overall Survival (OS) in mITT China Popluation
timeFrame: Baseline to end of study (approximately 58 months)
measure: Proportion of Participants Alive 12 Months in China Population
timeFrame: Randomization to 12 months post randomization
measure: Proportion of Participants Alive 18 Months in China Population
timeFrame: Randomization to 18 months post randomization
measure: Progression Free Survival (PFS) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status
timeFrame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
measure: Progression Free Survival (PFS) in mITT China Population
timeFrame: Randomisation to the first occurrence of disease progression or death (through the end of study, approximately 58 months)
measure: Objective Response Rate (ORR) in China Population With Programmed Death-Ligand 1 (PD-L1)-Positive Tumour Status
timeFrame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
measure: ORR in Modified Intent-To-Treat (mITT) China Popluation
timeFrame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
measure: Duration of Objective Response (DoR) in China Population
timeFrame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
measure: Clinical Benefit Rate (CBR) in China Population
timeFrame: 8 weeks for the first 12 months after treatment initiation and every 12 weeks thereafter until disease progression (through the end of study, approximately 58 months)
measure: Confirmed Objective Response Rate (C-ORR) in China Population
timeFrame: Baseline; every 8 weeks for the first 12 months after randomisation, and every 12 weeks thereafter until disease progression, withdrawal of consent, death, or study termination (approximately 58 months)
measure: Duration of Response for Confirmed Responders (C-DoR) in China Population
timeFrame: Time from the first occurrence of a documented objective response to disease progression or death (through the end of study, approximately 58 months)
measure: Time to Confirmed Deterioration (TTD) of GHS/QoL in China Population
timeFrame: Baseline to end of study (approximately 58 months)
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - Fort Myers (Broadway)
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists & Research Institute
state: Florida
city: Paramus
country: United States
facility: The Valley Hospital
state: New Jersey
city: Harrisburg
country: United States
facility: Magee-Woman's Hospital; UPMC Pinnacle Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Woman's Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Falls Church
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Buenos Aires
country: Argentina
facility: Fundación CENIT para la Investigación en Neurociencias
city: Rosario
country: Argentina
facility: Instituto de Oncología de Rosario
city: Rosario
country: Argentina
facility: Hospital Provincial del Centenario
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Center of the Republic of Srpska
city: Sarajevo
country: Bosnia and Herzegovina
facility: Clinical center University of Sarajevo
city: Fortaleza
country: Brazil
facility: Oncocentro Serviços Medicos E Hospitalares Ltda
state: CE
city: Goiania
country: Brazil
facility: Hospital Araujo Jorge; Departamento de Ginecologia E Mama
state: GO
city: Recife
country: Brazil
facility: Hospital do Cancer de Pernambuco - HCP
state: PE
city: Passo Fundo
country: Brazil
facility: Hospital Sao Vicente de Paulo
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: RS
city: Chapeco
country: Brazil
facility: Centro de Oncologia de Santa Catarina LTDA
state: SC
city: Sao Paulo
country: Brazil
facility: Instituto de Pesquisa Grupo NotreDame Intermedica
state: SP
city: Sao Paulo
country: Brazil
facility: Hospital Perola Byington
state: SP
city: Sao Paulo
country: Brazil
facility: Núcleo de Pesquisa São Camilo; ONCOLOGIA CLINICA / QUIMIOTERAPIA
state: SP
city: Puerto Montt
country: Chile
facility: Patagonia Research
city: Recoleta
country: Chile
facility: Bradford Hill Centro de Investigaciones Clinicas
city: Santiago
country: Chile
facility: Fundacion Arturo Lopez Perez
city: Santiago
country: Chile
facility: Clinica Vespucio
city: Temuco
country: Chile
facility: James Lind Centro de Investigación Del Cáncer
city: Vina Del Mar
country: Chile
facility: ONCOCENTRO APYS; Oncología
city: Beijing City
country: China
facility: Cancer Hospital , Chinese Academy of Medical
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Bengbu City
country: China
facility: the First Affiliated Hospital of Bengbu Medical College
city: Changchun
country: China
facility: Jilin Cancer Hospital
city: Chongqing
country: China
facility: The First Affiliated Hospital, Chongqing Medical University
city: Fuzhou City
country: China
facility: Fujian Medical University Union Hospital
city: Guangzhou
country: China
facility: Sun Yat-sen Memorial Hospital
city: Hangzhou City
country: China
facility: Sir Run Run Shaw Hospital Zhejiang University
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Jinan
country: China
facility: Shandong Cancer Hospital
city: Jinzhou City
country: China
facility: The First Affiliated Hospital Of Jinzhou Medical University
city: Nanjing
country: China
facility: Jiangsu Province Hospital
city: Qingdao
country: China
facility: The Affiliated Hospital of Medical College Qingdao University
city: Shanghai City
country: China
facility: Fudan University Shanghai Cancer Center; Medical Oncology
city: Shijiazhuang
country: China
facility: Hebei Medical University Fourth Hospital;(Tumor Hospital of Hebei Province)
city: Taiyuan City
country: China
facility: Shanxi Province Cancer Hospital
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Xi'an
country: China
facility: The First Affiliated Hospital of The Fourth Military Medical University (Xijing Hospital)
city: Zhejiang
country: China
facility: Zhejiang Cancer Hospital
city: La Habana
country: Cuba
facility: Hospital Hermanos Ameijeiras
city: La Habana
country: Cuba
facility: Instituto Nacional de Oncología y Radiología (INOR)
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital; Dept of Oncology
city: Tampere
country: Finland
facility: Tampere University Hospital; Dept of Oncology
city: Dijon
country: France
facility: Centre Georges-François Lecler; Ctr de Lutte Contre le Canc
city: Lyon
country: France
facility: Centre Leon Berard; Oncologie Genetique
city: Marseille Cedex 09
country: France
facility: Institut Paoli-Calmettes; Oncologie Medicale 1
city: Montpellier
country: France
facility: Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque
city: Rennes
country: France
facility: Centre Eugene Marquis; Service d'oncologie
city: St Cloud
country: France
facility: INSTITUT CURIE_SITE PARIS - Service d'Oncologie Médicale.
city: Vandoeuvre-les-nancy
country: France
facility: Centre Alexis Vautrin; Oncologie Medicale
city: Villejuif
country: France
facility: IGR
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus"; Frauenheilkunde und Geburtshilfe
city: Essen
country: Germany
facility: Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
city: Frankfurt
country: Germany
facility: Varisano Klinikum Frankfurt Höchst GmbH
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
city: München
country: Germany
facility: Medizinisches Zentrum für Hämatologie und Onkologie
city: Budapest
country: Hungary
facility: Szent Margit Hospital
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet; B Belgyogyaszati Osztaly
city: Budapest
country: Hungary
facility: Budapesti Uzsoki Utcai Kórház
city: Miskolc
country: Hungary
facility: Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi Oktato Korhaz;Sugarterapias Klinikai Onkologiai Intez
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem; Klinikai Központ Onkoterápiás Intézet
city: Napoli
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
state: Campania
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
state: Liguria
city: Milano
country: Italy
facility: Ospedale San Raffaele S.r.l.
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO); Ricerca Di Senologia Medica
state: Lombardia
city: Monza
country: Italy
facility: Ospedale San Gerardo
state: Lombardia
city: Candiolo
country: Italy
facility: Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
state: Piemonte
city: Brindisi
country: Italy
facility: Ospedale Antonio Perrino; Oncologia Medica
state: Puglia
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia
state: Toscana
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda
state: Veneto
city: Almaty
country: Kazakhstan
facility: Kazakh Scientific Research Institution Of Oncology and Radiology
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Cdmx
country: Mexico
facility: Centro Medico Dalinde
state: Mexico CITY (federal District)
city: Mexico City
country: Mexico
facility: CENEIT Oncologicos; DENTRO DE CONDOMINIO SAN FRANCISCO
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerologia; Oncology
city: Podgorica
country: Montenegro
facility: Clinical Center of Montenegro; Clinic for Oncology and Radiotherapy
city: FES
country: Morocco
facility: Centre Hospitalier Universitaire Hassan II
city: Marrakech
country: Morocco
facility: Centre Hospitalier Universitaire Mohamed VI; Oncologie-Hématologie
city: Marrakech
country: Morocco
facility: Clinique specialise Menara; Oncology Medical
city: Rabat
country: Morocco
facility: Institut National D'oncologie Sidi Med Benabdellah
city: Panama
country: Panama
facility: The Panama Clinic
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas
city: Kielce
country: Poland
facility: ?wi?tokrzyskie Centrum Onkologii; Dzia? Chemioterapii
city: Warszawa
country: Poland
facility: Narodowy Inst.Onkologii im.Sklodowskiej-Curie Panstw.Inst.Bad; Klinika Nowtw.Piersi i Chir.Rekonstr
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria; Servico de Oncologia Medica
city: Porto
country: Portugal
facility: Centro Hospitalar do Porto ? Hospital de Santo António; Oncologia
city: Moscovskaya Oblast
country: Russian Federation
facility: Moscow City Oncology Hospital #62
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: Moscow Clinical Scientific Center
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: FSBI "National Medical Research Center of Oncology N.N. Blokhin?
state: Moskovskaja Oblast
city: Saint-Petersburg
country: Russian Federation
facility: City Clinical Oncology Dispensary, SPb SBIH CCOD
state: Sankt Petersburg
city: Saint-Petersburg
country: Russian Federation
facility: FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
state: Sankt Petersburg
city: St. Petersburg
country: Russian Federation
facility: Private Healthcare Institution Clinical Hospital RZhD Medicine
state: Sankt Petersburg
city: Belgrade
country: Serbia
facility: Institute of Oncology and Radiology of Serbia
city: Belgrade
country: Serbia
facility: University Hospital Medical Center Bezanijska kosa
city: Nis
country: Serbia
facility: Clinical Centre Nis, Clinic for Oncology
city: Sremska Kamenica
country: Serbia
facility: Oncology Institute of Vojvodina
city: Singapore
country: Singapore
facility: National Cancer Centre; Medical Oncology
city: Johannesburg
country: South Africa
facility: Wits Clinical Research; Charlotte Maxeke Johannesburg Academic Hospital
city: Johannesburg
country: South Africa
facility: Medical Oncology Centre of Rosebank; Oncology
city: Pretoria
country: South Africa
facility: Private Oncology Centre
city: Bilbao
country: Spain
facility: Hospital de Cruces; Servicio de Oncologia
state: Vizcaya
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron; Oncology
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia; Servicio de Oncología
city: Ankara
country: Turkey
facility: Hacettepe University Medical Faculty; Department of Internal Medicine
city: Ankara
country: Turkey
facility: Ankara Oncology Hospital; Medical Oncology Department
city: Bornova, ?zm?r
country: Turkey
facility: Ege University Medical Faculty; Medical Oncology Department
city: Edirne
country: Turkey
facility: Trakya Universitesi Tip Fakultesi, Medikal Onkoloji Bilim Dali, Balkan Yerleskesi
city: Istanbul
country: Turkey
facility: Medipol University Medical Faculty; Oncology Department
city: Istanbul
country: Turkey
facility: Marmara University Pendik Training and Research Hospital; Medikal Onkoloji
city: Konya
country: Turkey
facility: Necmettin Erbakan University Meram Medical Faculty ; Internal Diseases
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre; Oncology Dept
city: Coventry
country: United Kingdom
facility: University Hospital Coventry
city: Edinburgh
country: United Kingdom
facility: Western General Hospital; Edinburgh Cancer Center
city: Lancaster
country: United Kingdom
facility: Royal Lancaster Infirmary, Morecambe Bay Hospitals Nhs Trust
city: London
country: United Kingdom
facility: Barts
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust, Guys Hospital
city: Manchester
country: United Kingdom
facility: Christie Hospital NHS Trust
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre
city: Stoke-on-Trent
country: United Kingdom
facility: Royal Stoke University Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: