A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC)

NCT ID: NCT02420821

Last Updated: 2023-01-30

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

915 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-05-20

Study Completion Date

2021-12-13

Brief Summary

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This multi-center, randomized, open-label study will evaluate the efficacy and safety of atezolizumab plus bevacizumab versus sunitinib in participants with inoperable, locally advanced, or metastatic RCC who have not received prior systemic active or experimental therapy, either in the adjuvant or metastatic setting.

Detailed Description

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Conditions

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Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Atezolizumab + Bevacizumab

Participants will receive both atezolizumab and bevacizumab until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.

Group Type EXPERIMENTAL

Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

Intervention Type DRUG

Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Days 1 and 22 of each 42-day cycle.

Bevacizumab

Intervention Type DRUG

Bevacizumab will be administered at a dose of 15 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 22 of each 42-day cycle.

Sunitinib

Participants will receive sunitinib until loss of clinical benefit, unacceptable toxicity or symptomatic deterioration attributed to disease progression, withdrawal of consent, or death, whichever occurs first.

Group Type ACTIVE_COMPARATOR

Sunitinib

Intervention Type DRUG

Sunitinib will be administered at a dose of 50 mg once daily, orally via capsule, on Day 1 through Day 28 of each 42-day cycle.

Interventions

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Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Days 1 and 22 of each 42-day cycle.

Intervention Type DRUG

Bevacizumab

Bevacizumab will be administered at a dose of 15 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 22 of each 42-day cycle.

Intervention Type DRUG

Sunitinib

Sunitinib will be administered at a dose of 50 mg once daily, orally via capsule, on Day 1 through Day 28 of each 42-day cycle.

Intervention Type DRUG

Other Intervention Names

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Tecentriq, MPDL3280A Avastin Sutent

Eligibility Criteria

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Inclusion Criteria

* Definitive diagnosis of unresectable locally advanced or metastatic RCC with clear-cell histology and/or a component of sarcomatoid carcinoma, with no prior treatment in the metastatic setting
* Evaluable Memorial Sloan Kettering Cancer Center risk score
* Measurable disease, as defined by RECIST v1.1
* Karnofsky performance status greater than or equal to 70%
* Adequate hematologic and end-organ function prior to randomization

Exclusion Criteria

Disease-Specific Exclusions:

* Radiotherapy for RCC within 14 days prior to treatment
* Active central nervous system disease
* Uncontrolled pleural effusion, pericardial effusion, or ascites
* Uncontrolled hypercalcemia
* Any other malignancies within 5 years except for low-risk prostate cancer or those with negligible risk of metastasis or death

General Medical Exclusions:

* Life expectancy less than 12 weeks
* Participation in another experimental drug study within 4 weeks prior to treatment
* Pregnant or lactating women
* Known hypersensitivity to any component of atezolizumab or other study medication
* History of autoimmune disease except controlled, treated hypothyroidism or type I diabetes mellitus
* History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis
* Positive human immunodeficiency virus test
* Active or chronic hepatitis B or C
* Severe infections within 4 weeks prior to treatment
* Exposure to oral or IV antibiotics within 2 weeks prior to treatment
* Live attenuated vaccines within 4 weeks prior to treatment (for influenza vaccination participants must agree not to receive live, attenuated influenza vaccine within 4 weeks prior to treatment, during treatment or within 5 months following the last dose)
* Significant cardiovascular disease
* Prior allogeneic stem cell or solid organ transplantation


* Prior treatment with cluster of differentiation 137 agonists, anti-cytotoxic T-lymphocyte associated protein-4, anti-programmed death (PD)-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents
* Treatment with immunostimulatory agents for non-malignant conditions within 6 weeks or immunosuppressive agents within 2 weeks prior to treatment

Bevacizumab- and Sunitinib-Specific Exclusions:

* History of hypertensive crisis or hypertensive encephalopathy
* Baseline electrocardiogram showing corrected QT interval greater than 460 milliseconds
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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University of Arizona Cancer Center

Tucson, Arizona, United States

Site Status

University of California at Irvine Medical Center; Department of Oncology

Orange, California, United States

Site Status

University of California

San Francisco, California, United States

Site Status

University of Colorado; Anschutz Cancer Pavilion

Aurora, Colorado, United States

Site Status

Rocky Mountain Cancer Center; Medical Oncology

Boulder, Colorado, United States

Site Status

Georgetown U; Lombardi Comp Can

Washington D.C., District of Columbia, United States

Site Status

Lynn Cancer Institute/Boca Raton Regional Hospital

Boca Raton, Florida, United States

Site Status

Florida Cancer Specialists - Port Charlotte

Port Charlotte, Florida, United States

Site Status

Florida Cancer Specialist, North Region

St. Petersburg, Florida, United States

Site Status

Piedmont Cancer Institute, PC

Atlanta, Georgia, United States

Site Status

The University of Chicago

Chicago, Illinois, United States

Site Status

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Dana Farber Cancer Inst.

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Comprehensive Cancer Centers of Nevada - Eastern Avenue

Las Vegas, Nevada, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

New York Oncology Hematology,P.C.-Albany

Albany, New York, United States

Site Status

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Oncology Hematology Care Inc

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic Foundation; Taussig Cancer Center

Cleveland, Ohio, United States

Site Status

Northwest Cancer Specialists, P.C.

Tigard, Oregon, United States

Site Status

SCRI Tennessee Oncology Chattanooga

Chattanooga, Tennessee, United States

Site Status

Sarah Cannon Cancer Center and Research Institute

Nashville, Tennessee, United States

Site Status

Vanderbilt Univ Medical Ctr

Nashville, Tennessee, United States

Site Status

Texas Oncology-Baylor Sammons Cancer Center

Dallas, Texas, United States

Site Status

Oncology and Hematology Associates of SW Virginia-Raonoke

Roanoke, Virginia, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Lifehouse

Camperdown, New South Wales, Australia

Site Status

Macquarie University Hospital

Macquarie Park, New South Wales, Australia

Site Status

Calvary Mater Newcastle; Medical Oncology

Waratah, New South Wales, Australia

Site Status

Icon Cancer Foundation

South Brisbane, Queensland, Australia

Site Status

Ashford Cancer Center Research

Kurralta Park, South Australia, Australia

Site Status

Austin Hospital; Medical Oncology

Heidelberg, Victoria, Australia

Site Status

St John of God Hospital

Murdoch, Western Australia, Australia

Site Status

University Clinical Centre of the Republic of Srpska

Banja Luka, , Bosnia and Herzegovina

Site Status

Hospital de Caridade de Ijui; Oncologia

Ijuí, Rio Grande do Sul, Brazil

Site Status

Santa Casa de Misericordia de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, Brazil

Site Status

Queen Elizabeth II Health Sciences Centre; Oncology

Halifax, Nova Scotia, Canada

Site Status

Royal Victoria Hospital

Barrie, Ontario, Canada

Site Status

Hamilton Health Sciences - Juravinski Cancer Centre

Hamilton, Ontario, Canada

Site Status

London Regional Cancer Centre

London, Ontario, Canada

Site Status

Lakeridge Health Oshawa; Oncology

Oshawa, Ontario, Canada

Site Status

The Ottawa Hospital Cancer Centre; Oncology

Ottawa, Ontario, Canada

Site Status

Sunnybrook Odette Cancer Centre

Toronto, Ontario, Canada

Site Status

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

CHU de Quebec Hotel-Dieu de Quebec

Québec, Quebec, Canada

Site Status

Masarykuv onkologicky ustav

Brno, , Czechia

Site Status

Fakultni nemocnice Olomouc; Onkologicka klinika

Olomouc, , Czechia

Site Status

Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika

Prague, , Czechia

Site Status

Thomayerova nemocnice

Praha 4 - Krc, , Czechia

Site Status

Aarhus Universitetshospital; Kræftafdelingen

Aarhus N, , Denmark

Site Status

Herlev Hospital; Afdeling for Kræftbehandling

Herlev, , Denmark

Site Status

Odense Universitetshospital, Onkologisk Afdeling R

Odense C, , Denmark

Site Status

ICO Paul Papin; Oncologie Medicale.

Angers, , France

Site Status

Hopital Saint Andre; Oncologie 2

Bordeaux, , France

Site Status

Centre Francois Baclesse; Urologie Gynecologie

Caen, , France

Site Status

Centre Oscar Lambret

Lille, , France

Site Status

Centre Léon Bérard

Lyon, , France

Site Status

Institut Paoli Calmettes; Oncologie Medicale

Marseille, , France

Site Status

Centre D'Oncologie de Gentilly; Oncology

Nancy, , France

Site Status

APHP - Hospital Saint Louis

Paris, , France

Site Status

Hopital Europeen Georges Pompidou; Service D'Oncologie Medicale

Paris, , France

Site Status

ICO - Site René Gauducheau

Saint-Herblain, , France

Site Status

Institut Gustave Roussy; Departement Oncologie Medicale

Villejuif, , France

Site Status

Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Urologie

Dresden, , Germany

Site Status

Universitätsklinikum Essen; Innere Klinik und Poliklinik für Tumorforschung

Essen, , Germany

Site Status

Nationales Centrum für Tumorerkrankungen Heidelberg (NCT); Thoraxklinik Heidelberg

Heidelberg, , Germany

Site Status

Klinikum d.Universität München Campus Großhadern

München, , Germany

Site Status

Universitätsklinikum Tübingen; Klinik für Urologie

Tübingen, , Germany

Site Status

Az. Osp. Cardarelli; Divisione Di Oncologia

Napoli, Campania, Italy

Site Status

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica

Meldola, Emilia-Romagna, Italy

Site Status

A.O. Universitaria Policlinico Di Modena; Oncologia

Modena, Emilia-Romagna, Italy

Site Status

Azienda Ospedaliera San Camillo Forlanini; Oncologia Medica

Rome, Lazio, Italy

Site Status

Irccs Ospedale San Raffaele;Oncologia Medica

Milan, Lombardy, Italy

Site Status

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

Milan, Lombardy, Italy

Site Status

Fondazione IRCCS Policlinico San Matteo, Oncologia

Pavia, Lombardy, Italy

Site Status

Azienda USL8 Arezzo-Presidio Ospedaliero 1 San Donato;U.O.C. Oncologia

Arezzo, Tuscany, Italy

Site Status

Nagoya University Hospital; Urology

Aichi, , Japan

Site Status

Chiba Cancer Center

Chiba, , Japan

Site Status

Kyushu University Hospital

Fukuoka, , Japan

Site Status

Gunma University Hospital

Gunma, , Japan

Site Status

Hokkaido University Hospital

Hokkaido, , Japan

Site Status

University of Tsukuba Hospital; Urology

Ibaraki, , Japan

Site Status

Yokohama City University Hospital

Kanagawa, , Japan

Site Status

Kitasato University Hospital

Kanagawa, , Japan

Site Status

Kumamoto University Hospital

Kumamoto, , Japan

Site Status

Niigata University Medical & Dental Hospital

Niigata, , Japan

Site Status

Iwate Medical University Hospital

Numakunai, , Japan

Site Status

Okayama University Hospital

Okayama, , Japan

Site Status

Osaka International Cancer Institute; Urology

Osaka, , Japan

Site Status

Osaka Metropolitan University Hospital

Osaka, , Japan

Site Status

Osaka University Hospital

Osaka, , Japan

Site Status

Kindai University Hospital

Osaka, , Japan

Site Status

Tokushima University Hospital

Tokushima, , Japan

Site Status

Toranomon Hospital

Tokyo, , Japan

Site Status

Tokyo Medical and Dental University Hospital

Tokyo, , Japan

Site Status

Nippon Medical School Hospital

Tokyo, , Japan

Site Status

The Cancer Institute Hospital, JFCR; Urology

Tokyo, , Japan

Site Status

Keio University Hospital

Tokyo, , Japan

Site Status

Tokyo Women's Medical University

Tokyo, , Japan

Site Status

Cancerología

Querétaro, , Mexico

Site Status

Centro Oncologico Estatal ISSEMYM

Toluca, , Mexico

Site Status

Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli

Lublin, , Poland

Site Status

Szpital Kliniczny; Przemienienia Panskiego;Uniwersytetu Medyczny im.; Karola Marcinkowskiego w Pozna

Poznan, , Poland

Site Status

Saint Elizabeth's Hospital

Warsaw, , Poland

Site Status

MAGODENT Sp. z o.o.

Warsaw, , Poland

Site Status

ALTAI REGIONAL ONCOLOGICAL CENTER; "Nadezhda" Clinic

Barnaul, Altayskiy Kray, Russia

Site Status

GBUZ Nizhegorodskay Region: Clinical Diagnostic Center

Nizhny Novgorod, Niznij Novgorod, Russia

Site Status

P.A. Herzen Oncological Inst. ; Oncology

Moscow, , Russia

Site Status

City Clinical Oncology Hospital

Moscow, , Russia

Site Status

National University Hospital

Singapore, , Singapore

Site Status

National Cancer Centre; Medical Oncology

Singapore, , Singapore

Site Status

Chungnam National University Hospital

Daejeon, , South Korea

Site Status

National Cancer Center

Goyang-si, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam-si, , South Korea

Site Status

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, Spain

Site Status

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, Spain

Site Status

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

Site Status

Hospital Clínic i Provincial; Servicio de Oncología

Barcelona, , Spain

Site Status

Hospital Duran i Reynals; Oncologia

Barcelona, , Spain

Site Status

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

Seville, , Spain

Site Status

Taichung Veterans General Hospital; Division of Urology

Taichung, , Taiwan

Site Status

National Taiwan Uni Hospital; Dept of Oncology

Taipei, , Taiwan

Site Status

Chang Gung Medical Foundation-Linkou, Urinary Oncology

Taoyuan District, , Taiwan

Site Status

Chulalongkorn Hospital; Medical Oncology

Bangkok, , Thailand

Site Status

Ramathibodi Hospital; Dept of Med.-Div. of Med. Onc

Bangkok, , Thailand

Site Status

Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology

Bangkok, , Thailand

Site Status

Maharaj Nakorn Chiangmai Hospital; Department of Surgery/ Urology unit

Chiang Mai, , Thailand

Site Status

Songklanagarind Hospital; Department of Oncology

Songkhla, , Thailand

Site Status

Hacettepe University Medical Faculty

Ankara, , Turkey (Türkiye)

Site Status

Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department

Edirne, , Turkey (Türkiye)

Site Status

Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology

Istanbul, , Turkey (Türkiye)

Site Status

Clatterbridge Cancer Centre

Bebington, , United Kingdom

Site Status

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status

Royal Blackburn Hospital

Blackburn, , United Kingdom

Site Status

Addenbrookes Nhs Trust; Oncology Clinical Trials Unit

Cambridge, , United Kingdom

Site Status

Barts Health NHS Trust - St Bartholomew's Hospital

London, , United Kingdom

Site Status

Royal Free Hospital; Dept of Oncology

London, , United Kingdom

Site Status

Christie Hospital Nhs Trust; Medical Oncology

Manchester, , United Kingdom

Site Status

Churchill Hospital; Oxford Cancer and Haematology Centre

Oxford, , United Kingdom

Site Status

Southampton General Hospital; Medical Oncology

Southampton, , United Kingdom

Site Status

Royal Marsden Hospital; Dept of Medical Oncology

Sutton, , United Kingdom

Site Status

Singleton Hospital; Pharmacy Department

Swansea, , United Kingdom

Site Status

Countries

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United States Australia Bosnia and Herzegovina Brazil Canada Czechia Denmark France Germany Italy Japan Mexico Poland Russia Singapore South Korea Spain Taiwan Thailand Turkey (Türkiye) United Kingdom

References

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Aldin A, Besiroglu B, Adams A, Monsef I, Piechotta V, Tomlinson E, Hornbach C, Dressen N, Goldkuhle M, Maisch P, Dahm P, Heidenreich A, Skoetz N. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2023 May 4;5(5):CD013798. doi: 10.1002/14651858.CD013798.pub2.

Reference Type DERIVED
PMID: 37146227 (View on PubMed)

Motzer RJ, Powles T, Atkins MB, Escudier B, McDermott DF, Alekseev BY, Lee JL, Suarez C, Stroyakovskiy D, De Giorgi U, Donskov F, Mellado B, Banchereau R, Hamidi H, Khan O, Craine V, Huseni M, Flinn N, Dubey S, Rini BI. Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients With Previously Untreated Metastatic Renal Cell Carcinoma. JAMA Oncol. 2022 Feb 1;8(2):275-280. doi: 10.1001/jamaoncol.2021.5981.

Reference Type DERIVED
PMID: 34940781 (View on PubMed)

Atkins MB, Rini BI, Motzer RJ, Powles T, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Gurney H, Oudard S, Uemura M, Lam ET, Grullich C, Quach C, Carroll S, Ding B, Zhu QC, Piault-Louis E, Schiff C, Escudier B. Patient-Reported Outcomes from the Phase III Randomized IMmotion151 Trial: Atezolizumab + Bevacizumab versus Sunitinib in Treatment-Naive Metastatic Renal Cell Carcinoma. Clin Cancer Res. 2020 Jun 1;26(11):2506-2514. doi: 10.1158/1078-0432.CCR-19-2838. Epub 2020 Mar 3.

Reference Type DERIVED
PMID: 32127394 (View on PubMed)

Rini BI, Powles T, Atkins MB, Escudier B, McDermott DF, Suarez C, Bracarda S, Stadler WM, Donskov F, Lee JL, Hawkins R, Ravaud A, Alekseev B, Staehler M, Uemura M, De Giorgi U, Mellado B, Porta C, Melichar B, Gurney H, Bedke J, Choueiri TK, Parnis F, Khaznadar T, Thobhani A, Li S, Piault-Louis E, Frantz G, Huseni M, Schiff C, Green MC, Motzer RJ; IMmotion151 Study Group. Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial. Lancet. 2019 Jun 15;393(10189):2404-2415. doi: 10.1016/S0140-6736(19)30723-8. Epub 2019 May 9.

Reference Type DERIVED
PMID: 31079938 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2014-004684-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WO29637

Identifier Type: -

Identifier Source: org_study_id

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