Clinical trial NCT02291289: A Study of Biomarker-Driven Therapy in Metastatic Colorectal Cancer (mCRC)
Official title: A Multi-Centre Randomised Clinical Trial of Biomarker-Driven Maintenance Treatment for First-Line Metastatic Colorectal Cancer (MODUL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2014-11-14
Enrollment: 1044
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 randomized, multi-center, active-controlled, open-label, parallel-group study will investigate the efficacy and safety of biomarker-driven maintenance treatment for first-line mCRC. Participants with mCRC are eligible for entry and cannot have received any prior chemotherapy in the metastatic setting. The entire study duration is anticipated to be approximately 7.5 years.


Eligibility criteria: Inclusion Criteria:

* ECOG PS of less than or equal to (\<=) 2
* At least 16 weeks of life expectancy at time of entry into the study
* Histologically confirmed colorectal cancer (CRC) with mCRC confirmed radiologically
* Measureable, unresectable disease according to RECIST 1.1
* No prior chemotherapy for CRC in the metastatic setting
* Archival tumor formalin-fixed paraffin-embedded tissue block from the primary tumor obtained at the time of the initial diagnosis is available
* Adequate hematological, liver and renal function
* Agreement to use highly effective measures of contraception

Exclusion Criteria for All Participants:

* Less than 6 months from completion of any prior neoadjuvant or adjuvant chemotherapy, radiotherapy
* Prior or current treatment with bevacizumab or any other anti-angiogenic drug (vascular endothelial growth factor or vascular endothelial growth factor receptor therapies or tyrosine kinase inhibitors)
* Current or recent (within 10 days of study enrollment) use of aspirin (more than \[\>\] 325 milligrams per day \[mg/day\]), clopidogrel (\> 75 mg/day), or current or recent (within 10 days prior to the start of study induction treatment) use of therapeutic oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (prophylactic uses allowed)
* Active infection requiring intravenous antibiotics at the start of study induction treatment
* Previous or concurrent malignancy, except for adequately treated basal or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the participant has been disease-free for 5 years prior to study entry
* Inadequately controlled hypertension; prior history of hypertensive crisis or hypertensive encephalopathy
* Clinically significant (active) cardiovascular disease, for example cerebrovascular accidents \<= 6 months prior to start of study induction treatment, myocardial infarction \<= 6 months prior to study enrollment, unstable angina, New York Heart Association (NYHA) Functional Classification Grade II or greater congestive heart failure, or serious cardiac arrhythmia uncontrolled by medication or potentially interfering with protocol treatment
* Significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of start of study induction treatment
* Active symptomatic or untreated central nervous system (CNS) metastases; CNS disease other than supratentorial or cerebellar metastases (in other words, patients with metastases to midbrain, pons, medulla or spinal cord are excluded); history of or known carcinomatous meningitis
* Known hypersensitivity to any component of any of the study induction or maintenance treatment medications
* Pregnancy or lactation

Exclusion Criteria for Participants in Cohort 1 (MP):

* Inability to swallow pills
* Refractory nausea and vomiting, malabsorption, external biliary shunt or significant bowel resection that would preclude adequate absorption
* History or presence of clinically significant ventricular or atrial dysrhythmias
* Corrected QT (QTc) interval \>= 450 millisecond assessed within 3 weeks prior to randomization, long QT syndrome or, uncorrectable electrolyte abnormalities (including magnesium) or requirement for medicinal products known to prolong the QT interval
* ECOG PS \> 2

Exclusion Criteria for Participants in Cohort 2 (MP):

* History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
* Prior allogeneic bone marrow transplantation or prior solid organ transplantation
* History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis at most recent chest imaging (computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\])
* Positive test for human immunodeficiency virus (HIV)
* Active hepatitis B virus (HBV) or hepatitis C virus (HCV) at Screening
* Active tuberculosis
* Severe infection within 4 weeks prior to start of maintenance treatment including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia; has signs or symptoms of significant infection or has received oral or IV antibiotics within 2 weeks prior to start of maintenance treatment
* Administration of a live, attenuated vaccine within 4 weeks prior to start of maintenance treatment or anticipation that such a live attenuated vaccine will be required during the remainder of the study
* Prior treatment with cluster of differentiation (CD) 137 agonists, anti-cytotoxic T-lymphocyte-associated antigen (CTLA) 4, anti-programmed death-1 (PD-1), or anti-programmed death-ligand 1 (PD-L1) therapeutic antibody or pathway-targeting agents
* Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to start of maintenance treatment
* Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to start of maintenance treatment, or anticipated requirement for systemic immunosuppressive medications during the remainder of the study
* If receiving receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor (for example, denosumab) and unwilling to adopt alternative treatment such as bisphosphonates while receiving atezolizumab

Exclusion Criteria for Participants in Cohort 3 (MP):

* Inability to swallow pills
* Left ventricular ejection fraction (LVEF) less than (\<) 50 percent (%) as assessed after completion of induction treatment by either 2-dimensional echocardiogram or multiple-gated acquisition
* Clinically significant cardiovascular disease, including unstable angina, history of or active congestive heart failure of ≥ NYHA Grade 2, history of or ongoing serious cardiac arrhythmia requiring treatment (except for controlled atrial fibrillation and/or paroxysmal supraventricular tachycardia).
* Current uncontrolled hypertension with or without medication
* Current dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy
* Insulin-dependent diabetes
* Current known infection with HIV, HBV, or HCV (active infection or carriers)
* Requirement for concurrent use of the antiviral agent sorivudine (antiviral) or chemically related analogues, such as brivudine
* Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, or ulcerative colitis
* Known hypersensitivity to murine proteins

Exclusion Criteria for Participants in Cohort 4 (MP):

* Inability to swallow medications
* History of autoimmune disease including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
* History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on most recent chest imaging (CT scan or MRI)
* Malabsorption condition that would alter the absorption of orally administered medications
* Amylase or lipase ≥ 1.5 times the upper limit of normal within 14 days prior to maintenance treatment initiation
* Serum albumin less than (\<) 2.5 grams per deciliter (g/dL)
* LVEF \< institutional lower limit of normal or \< 50%, whichever is lower
* Poorly controlled hypertension
* Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters are allowed
* Unstable angina, new onset angina within last 3 months, myocardial infarction within last 6 months and current congestive heart failure ≥ NYHA Grade 2
* History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to initiation of maintenance treatment
* History or evidence of intracranial hemorrhage or spinal cord hemorrhage
* Evidence of clinically significant vasogenic edema
* Any hemorrhage or bleeding event ≥ National Cancer Institute Common Terminology Criteria for Adverse Events Grade 3 within 28 days prior to initiation of maintenance treatment
* History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion, or neovascular macular degeneration
* Positive HIV test
* Active HBV or HCV
* Active tuberculosis
* Severe infection within 4 weeks prior to start of maintenance treatment including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia; has signs or symptoms of significant infection or has received oral or IV antibiotics within 2 weeks prior to start of maintenance treatment.
* Prior allogeneic bone marrow transplantation or prior solid organ transplantation
* Administration of a live, attenuated vaccine within 4 weeks prior to start of study maintenance treatment or anticipation that such a live attenuated vaccine will be required during the study
* Prior treatment with CD137 agonists, anti-CTLA4, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
* Prior treatment with a mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) or ERK inhibitor
* Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin-2) within 4 weeks or five half-lives of the drug, whichever is longer, prior to start of study maintenance treatment
* Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to start of study maintenance treatment, or requirement for systemic immunosuppressive medications during the trial.
* If receiving a RANKL inhibitor (for example, denosumab), unwilling to adopt alternative treatment such as (but not limited to) bisphosphonates, while receiving atezolizumab.
* Consumption of foods, supplements or drugs that are potent cytochrome P450 3A4 (CYP3A4) enzyme inducers or inhibitors ≤ 7 days before initiation of study maintenance treatment or expected concomitant use during maintenance treatment. These include St. John's wort or hyperforin (potent CYP3A4 enzyme inducer) and grapefruit juice (potent CYP3A4 enzyme inhibitor)

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: From randomization until disease progression or death from any cause, up to 5 years
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: From randomization until death from any cause, up to 5 years
measure: Percentage of Participants With Adverse Events
timeFrame: From baseline until end of study (up to 5 years)
measure: Overall Response
timeFrame: From randomization until disease progression, up to 5 years
measure: Disease Control Rate (DCR)
timeFrame: From randomization until disease progression, up to 5 years
measure: Time to Treatment Response
timeFrame: From randomization until disease progression or death from any cause, up to 5 years
measure: Duration of Response
timeFrame: From first objective response until disease progression or death from any cause, up to 5 years
measure: Percentage of Participants With Improvement and/or Stayed the Same on the Eastern Cooperative Oncology Group Performance Status (ECOG PS) Score
timeFrame: From baseline until end of study (up to 5 years)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital de Gastroenterologia Dr. Bonorino Udaondo ; Servicio de Oncología
city: La Rioja
country: Argentina
facility: Centro Oncologico Riojano Integral (CORI)
city: Viedma Rio Negro
country: Argentina
facility: Clínica Viedma
city: Brussels
country: Belgium
facility: Institut Jules Bordet X
city: Bruxelles
country: Belgium
facility: Hospital Erasme
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Liege
country: Belgium
facility: CHC MontLégia
city: Roeselare
country: Belgium
facility: AZ Delta (Campus Rumbeke)
city: Banja Luka
country: Bosnia and Herzegovina
facility: University Clinical Center of the Republic of Srpska
city: Passo Fundo
country: Brazil
facility: Hospital da Cidade de Passo Fundo; Centro de Pesquisa em Oncologia
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: RS
city: Porto Alegre
country: Brazil
facility: Hospital Nossa Senhora da Conceicao
state: RS
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: SP
city: Jau
country: Brazil
facility: Hospital Amaral Carvalho
state: SP
city: Sao Jose do Rio Preto
country: Brazil
facility: Faculdade de Medicina de Sao Jose do Rio Preto - FAMERP*X*
state: SP
city: Sao Paulo
country: Brazil
facility: Instituto de Ensino e Pesquisa Sao Lucas - IEP
state: SP
city: Herlev
country: Denmark
facility: Herlev Hospital; Afdeling for Kræftbehandling
city: Herning
country: Denmark
facility: Regionshospitalet Gødstrup; Kræftafdelingen
city: København Ø
country: Denmark
facility: Rigshospitalet; Onkologisk Klinik
city: Odense C
country: Denmark
facility: Odense Universitetshospital, Onkologisk Afdeling R
city: Roskilde
country: Denmark
facility: Sygehus Syd Roskilde; Onkologisk/haematologisk ambulatorium
city: Cairo
country: Egypt
facility: National Cancer Institute
city: Cairo
country: Egypt
facility: Ain Shams University Hospital; Oncology
city: Avignon
country: France
facility: Clinique Sainte Catherine
city: Besancon
country: France
facility: HOPITAL JEAN MINJOZ; Oncologie
city: Brest
country: France
facility: Hopital Augustin Morvan; Federation De Cancerologie
city: Clermont Ferrand
country: France
facility: Chu Estaing; Chir Generale Digestive A Et B
city: Levallois-Perret
country: France
facility: Hôpital Franco-Britannique- Fondation Cognacq-Jay; Cancerologie
city: Lille
country: France
facility: Hopital Claude Huriez; Medecine Interne Oncologie
city: Montbeliard
country: France
facility: Ch De Montbeliard;Chir Generale Digestive
city: Nimes
country: France
facility: Hopital Caremeau; Gastro Enterologie
city: Paris
country: France
facility: Hopital Saint Antoine; Oncologie Medicale
city: Pessac
country: France
facility: Hopital Haut Leveque
city: Poitiers
country: France
facility: Chu La Miletrie; Gastro Enterologie Endoscopies
city: Strasbourg
country: France
facility: ICANS
city: Toulouse
country: France
facility: Hopital Rangueil; Gastro Enterologie Et Nutrition
city: Villejuif
country: France
facility: Institut Gustave Roussy; Departement Oncologie Medicale
city: Augsburg
country: Germany
facility: Hämatologie Onkologie im Zentrum MVZ GmbH
city: Berlin
country: Germany
facility: Onkologische Schwerpunktpraxis Kurfürstendamm
city: Berlin
country: Germany
facility: DRK Kliniken Berlin Köpenick Darmzentrum
city: Dresden
country: Germany
facility: BAG Freiberg-Richter, Jacobasch, Illmer, Wolf; Gemeinschaftspraxis Hämatologie-Onkologie
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest; Klinik f. Onkologie und Hämatologie
city: Frechen
country: Germany
facility: PIOH PD Dr. R. Schnell ? Dr. H. Schulz ? Dr. M. Hellmann
city: Fulda
country: Germany
facility: Klinik Fulda, Medizinisches Versorgungszentrum Osthessen GmbH
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Onkologisches Zentrum, Studienzentrale der II. Med. Klinik
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover; Zentrum Innere Medizin; Abt. Hämatologie u. Onkologie
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH; Klinik für Innere Medizin III; Schwerpunkt Häma./Onko./Palliativm.
city: Herne
country: Germany
facility: Klinik der Ruhr-Uni Bochum; Marien-Hospital Herne
city: Lebach
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und Onkologie, PD Dr. Bauer, Dr. Thiel
city: Magdeburg
country: Germany
facility: Onkologische Gemeinschaftspraxis
city: Magdeburg
country: Germany
facility: Klinikum Magdeburg gGmbH Klinik für Allgemein- und Viszeralchirurgie
city: Mageburg
country: Germany
facility: Universitätsklinikum Magdeburg Klinik für Gastroenterologie und Hepatologie
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH, Krankenhaus St. Franziskus
city: München
country: Germany
facility: Städt. Klinikum München GmbH Klinikum Neuperlach Klinik f.Hämatologie u.Onkologie
city: Münster
country: Germany
facility: Gemeinschaftspraxis für Hämatologie und Onkologie
city: Paderborn
country: Germany
facility: Brüderkrankenhaus St. Josef
city: Ravensburg
country: Germany
facility: Studienzentrum Onkologie Ravensburg GbR; Onkologie Ravensburg
city: Recklinghausen
country: Germany
facility: Prosper-Hospital, Medizinische Klinik I
city: Regensburg
country: Germany
facility: Krankenhaus Barmherziger Brüder; Klinik für Internistische Onkologie / Hämatologie
city: Reutlingen
country: Germany
facility: Klinikum am Steinenberg / Ermstalklinik
city: Saarbruecken
country: Germany
facility: Praxis für Hämatologie & Onkologie
city: Stade
country: Germany
facility: MVZ für Hämatologie, Onkologie, Strahlentherapie und Palliativmedizin -; Klinik Dr. Hancken
city: Trier
country: Germany
facility: Klinikum Mutterhaus der Borromaeerinnen gGmbH; Haematologie/Onkologie
city: Wetzlar
country: Germany
facility: Klinikum Wetzlar-Braunfels, Klinik für Hämatologie/Onkologie und Palliativmedizin
city: Athens
country: Greece
facility: Agioi Anargyroi; 3Rd Dept. of Medical Oncology
city: Heraklion
country: Greece
facility: Univ General Hosp Heraklion; Medical Oncology
city: Ioannina
country: Greece
facility: Uni Hospital of Ioannina; Oncology Dept.
city: Patras
country: Greece
facility: University Hospital of Patras Medical Oncology
city: Thermi Thessalonikis
country: Greece
facility: Thermi Clinic; Oncology Clinic
city: Thessaloniki
country: Greece
facility: Bioclinic Thessaloniki
city: Thessaloniki
country: Greece
facility: Euromedical General Clinic of Thessaloniki; Oncology Department
city: Napoli
country: Italy
facility: IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A
state: Campania
city: Meldola
country: Italy
facility: IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
state: Emilia-Romagna
city: Parma
country: Italy
facility: A.O. Universitaria Di Parma; Oncologia Medica
state: Emilia-Romagna
city: Roma
country: Italy
facility: Istituto Regina Elena; Oncologia Medica A
state: Lazio
city: Roma
country: Italy
facility: Policlinico Universitario "Agostino Gemelli"; U.O.C. Oncologia Medica
state: Lazio
city: Bergamo
country: Italy
facility: Humanitas Gavazzeni;U.O. Oncologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
state: Lombardia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia
state: Lombardia
city: San Giovanni Rotondo
country: Italy
facility: IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia
state: Puglia
city: Firenze
country: Italy
facility: Azienda Ospedaliero-Universitaria Careggi;S.C. Oncologia Medica 1
state: Toscana
city: Padova
country: Italy
facility: IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima
state: Veneto
city: Verona
country: Italy
facility: A.O.U.I. VERONA-OSPEDALE POLICLINICO G.B. ROSSI BORGO ROMA;ONCOLOGIA MEDICA-d.U.
state: Veneto
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: León
country: Mexico
facility: Fundacion Rodolfo Padilla Padilla A.C.
state: Guanajuato
city: Oaxaca de Juárez
country: Mexico
facility: Oaxaca Site Management Organization
state: Oaxaca
city: Queretaro, Queretaro
country: Mexico
facility: Cancerologia de Queretaro; Oncologia
state: Queretaro
city: Mexico City
country: Mexico
facility: Instituto Nacional de Cancerologia; Oncology
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek Ziekenhuis
city: Capelle A/d IJssel
country: Netherlands
facility: Ijsselland Ziekenhuis; Inwendige Geneeskunde
city: Deventer
country: Netherlands
facility: Deventer Ziekenhuis; Interne Geneeskunde
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis - loc Dordrecht
city: Eindhoven
country: Netherlands
facility: Catharina ZKHS; Inwendige Geneeskunde Afd.
city: Utrecht
country: Netherlands
facility: St. Antonius locatie Leidsche Rijn
city: Zwolle
country: Netherlands
facility: Isala Klinieken
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Klinika Onkologii i Radioterapii,
city: Coimbra
country: Portugal
facility: HUC; Servico de Oncologia Medica
city: Lisboa
country: Portugal
facility: Hospital de Santa Maria; Servico de Oncologia Medica
city: UFA
country: Russian Federation
facility: Bashkirian Republican Clinical Oncology Dispensary
state: Baskortostan
city: Moscow
country: Russian Federation
facility: Russian Oncology Research Center n.a. N.N. Blokhin Dpt of Clinical Pharmacology and Chemotherapy
state: Moskovskaja Oblast
city: Belgrade
country: Serbia
facility: Institute for Oncology and Radiology of Serbia; Clinic for Medical Oncology
city: Bratislava
country: Slovakia
facility: Narodny Onkologicky Ustav; Oddelenie klinickej onkologie E
city: Poprad
country: Slovakia
facility: POKO Poprad; Department of Oncology
city: Ljubljana
country: Slovenia
facility: Institute of Oncology Ljubljana
city: Elche
country: Spain
facility: Hospital General Universitario de Elche; Servicio de Oncologia
state: Alicante
city: Oviedo
country: Spain
facility: Hospital Univ. Central de Asturias; Servicio de Oncologia
state: Asturias
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
state: Barcelona
city: Sant Andreu de La Barca
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla; Servicio de Oncologia
state: Cantabria
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia; Servicio de Oncologia
state: Cordoba
city: San Sebastian
country: Spain
facility: Hospital de Donostia; Servicio de Oncologia Medica
state: Guipuzcoa
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Islas Baleares
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
state: LA Coruña
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro; Servicio de Oncologia
state: Madrid
city: Santa Cruz de Tenerife
country: Spain
facility: Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Oncologia
state: Tenerife
city: Alicante
country: Spain
facility: Hospital General Univ. de Alicante; Servicio de Oncologia
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia
city: Lerida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia
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: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de Oncologia
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya; Servicio de Oncologia
city: Navarra
country: Spain
facility: Hospital de Navarra; Servicio de Oncologia
city: Orense
country: Spain
facility: Complejo Hospitalario de Orense; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia; Servicio de oncologia
city: Valencia
country: Spain
facility: Hospital Universitario la Fe; Servicio de Oncologia
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa; Servicio de Oncologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Oncologia
city: Lund
country: Sweden
facility: Skånes University Hospital, Skånes Department of Onclology
city: Stockholm
country: Sweden
facility: Karolinska Hospital; Oncology - Radiumhemmet
city: Adana
country: Turkey
facility: Acibadem University School of Medicine, Adana Hospital; General Surgery
city: Edirne
country: Turkey
facility: Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
city: Istanbul
country: Turkey
facility: Istanbul Uni Capa Medical Faculty; Inst. of Oncology
city: Istanbul
country: Turkey
facility: Marmara Uni Faculty of Medicine; Medical Oncology
city: Izmir
country: Turkey
facility: Ege Uni Medical Faculty Hospital; Oncology Dept
city: Sihhiye/Ankara
country: Turkey
facility: Hacettepe Uni Medical Faculty Hospital; Oncology Dept
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary; Medical Oncology Dept
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: Chelsmford
country: United Kingdom
facility: Broomfield Hospital; Oncology
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital; The Queens Centre for Oncology and Haematology
city: London
country: United Kingdom
facility: Guys and St Thomas NHS Foundation Trust, Guys Hospital
city: London
country: United Kingdom
facility: Royal Marsden Hospital; Dept of Med-Onc
city: Manchester
country: United Kingdom
facility: Christie Hospital Nhs Trust; Medical Oncology
city: Middlesex
country: United Kingdom
facility: Mount Vernon Hospital
city: Romford
country: United Kingdom
facility: Queen's Hospital
city: Southampton
country: United Kingdom
facility: Southampton General Hospital; Medical Oncology
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital; Dept. of Medicine
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: