MedPath

A Study of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy (KATHERINE)

Phase 3
Completed
Conditions
Breast Cancer
Interventions
Registration Number
NCT01772472
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This 2-arm, randomized, open-label study will evaluate the efficacy and safety of trastuzumab emtansine versus trastuzumab as adjuvant therapy in patients with HER2-positive breast cancer who have residual tumor present in the breast or axillary lymph nodes following preoperative therapy. Eligible patients will be randomized to receive either trastuzumab emtansine 3.6 mg/kg or trastuzumab 6 mg/kg intravenously every 3 weeks for 14 cycles. Radiotherapy and/or hormone therapy will be given in addition if indicated.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1487
Inclusion Criteria
  • Adult patient, >/= 18 years of age
  • HER2-positive breast cancer
  • Histologically confirmed invasive breast carcinoma
  • Clinical stage T1-4/N0-3/M0 at presentation (patients with T1a/bN0 tumors will not be eligible)
  • Completion of preoperative systemic chemotherapy and HER2-directed treatment consisting of at least 6 cycles of chemotherapy with a total duration of at least 16 weeks, including at least 9 weeks of trastuzumab and at least 9 weeks of taxane-based therapy
  • Adequate excision: surgical removal of all clinically evident disease in the breast and lymph nodes as specified in protocol
  • Pathological evidence of residual invasive carcinoma in the breast or axillary lymph nodes following completion of preoperative therapy
  • An interval of no more than 12 weeks between the date of surgery and the date of randomization
  • Known hormone-receptor status
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate hematologic, renal and liver function
  • Screening Left ventricular ejection fraction (LVEF) >/= 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) after receiving neoadjuvant chemotherapy and no decrease in LVEF by more than 15% absolute points from the pre-chemotherapy LVEF. Or, if pre-chemotherapy LVEF was not assessed, the screening LVEF must be >/= 55% after completion of neoadjuvant chemotherapy.
  • For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study drug
  • Documentation of hepatitis B virus and hepatitis C virus serology is required
Exclusion Criteria
  • Stage IV (metastatic) breast cancer
  • History of any prior (ipsi- or contralateral breast cancer except lobular carcinoma in situ
  • Evidence of clinically evident gross residual or recurrent disease following preoperative therapy and surgery
  • Progressive disease during preoperative systemic therapy
  • Treatment with any anti-cancer investigational drug within 28 days prior to commencing study treatment
  • History of other malignancy within the last 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other non-breast malignancies with a similar outcome to those mentioned above
  • Patients for whom radiotherapy would be recommended for breast cancer treatment but for whom it is contraindicated because of medical reasons
  • Current NCI CTCAE (Version 4.0) Grade >/= 2 peripheral neuropathy
  • History of exposure to the following cumulative doses of anthracyclines: Doxorubicin > 240 mg/m2; Epirubicin or Liposomal Doxorubicin-Hydrochloride (Myocet®) > 480 mg/m2; For other anthracyclines, exposure equivalent to doxorubicin > 240 mg/m2
  • Cardiopulmonary dysfunction as defined by protocol
  • Prior treatment with trastuzumab emtansine
  • Current severe, uncontrolled systemic disease
  • Pregnant or lactating women
  • Any known active liver disease, e.g. due to HBV, HCV, autoimmune hepatic disorders, or sclerosing cholangitis
  • Concurrent serious uncontrolled infections requiring treatment or known infection with HIV
  • History of intolerance, including Grade 3 to 4 infusion reaction or hypersensitivity to trastuzumab or murine proteins or any components of the product

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Trastuzumabtrastuzumab-
Trastuzumab emtansinetrastuzumab emtansine-
Primary Outcome Measures
NameTimeMethod
Invasive Disease-free Survival (IDFS)From randomization to data cut-off date of 25 July 2018 (approximately up to 64 months)

IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. 3-year IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.

Secondary Outcome Measures
NameTimeMethod
Invasive Disease-free Survival Including Second Primary Non-breast CancerFrom baseline up to 12 years

IDFS including second primary non-breast cancer was defined the same way as IDFS for the primary endpoint but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and carcinoma in situ (CIS) of any site). 3-year IDFS including second primary non-breast cancer event-free rates per treatment arm in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.

Disease-free SurvivalFrom baseline up to 12 years

Disease-free survival was defined as the time between randomization and the date of the first occurrence of an invasive disease-free survival event including second primary non-breast cancer event or contralateral or ipsilateral DCIS. 3-year DFS event-free rates per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after randomization.

Overall Survival (OS)Baseline up to 12 years

Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause. 5 years OS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 5 years after treatment.

Distant Recurrence-Free Interval (DRFI)Baseline up to 12 years

DRFI was defined as the time between randomization and the date of distant breast cancer recurrence. 3 years DRFI event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment.

Percentage of Participants With Adverse EventsFrom Day 1 to 30 days after last dose of study drug, up to the clinical cutoff date (approximately 64 months)

An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. AEs, including AEs of Special Interest and AEs of Particular Interest, were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). Reported are the number of subjects with AEs, Grade 3-5 AEs, and Serious Adverse Events (SAEs).

Percentage of Participants With Cardiac DysfunctionFrom baseline up to 12 years

Cardiac events were reported based on the NCI-CTCAE, v4.0.

Change From Baseline of Functional Scales, Symptom Scales and Single Items in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30)Baseline, Cycle 5, 11, Follow-up (FU) Month 6, Follow-up Month 12

The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale \[1 'very poor' to 7 'Excellent'\]). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be a minimally important difference to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1).

Change From Baseline of Four Functioning Scales and Four Symptom Scales in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Breast Cancer (QLQ-BR23)Baseline, Cycle 5, 11, Follow-up Month 6, Follow-up Month 12

EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective \[FP\]) and four symptom scales (systemic side effects \[SE\], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Higher scores for symptom scales represent higher levels of symptoms/problems. For functional scales, positive change from baseline indicated deterioration in quality of life (QOL) and negative change from baseline indicated an improvement in QOL. For symptom scales, positive change from baseline indicated an improvement in quality of life (QOL) and negative change from baseline indicated a deterioration in QOL.

Serum Concentrations (Area Under the Concentration-time Curve [AUC]) of Trastuzumab Emtansine (Including Total Trastuzumab and DM1)Cycle (C) 1, Day (D) 1 and C4D1 of pre-infusion, C1D1 and C4D1 post-infusion, C2D1 and C5D1 pre-infusion and study treatment termination

Blood and serum samples for measurement of trastuzumab emtansine, total trastuzumab, and DM1 will be obtained from patients randomized to the trastuzumab emtansine arm.

Serum Concentrations (AUC) of TrastuzumabC1D1 and C4D1 of post-infusion and study treatment termination

Serum blood samples were collected for trastuzumab measurement prior to dosing and 15-30 minutes post infusion for Cycle 1 and Cycle 4. Additional serum samples were collected at study treatment termination.

Plasma Concentrations of DM1Day 1 on Cycles 1 and 4. Each cycle is 21 days.
Trastuzumab Emtansine ExposureDay 1 on Cycles 1, 2, 4 and 5, at study treatment termination and 3-4 months after last dose of trastuzumab emtansine. Each cycle is 21 days.
Anti-trastuzumab Emtansine Antibody (ATA)Day 1 on Cycles 1, and 4, at study treatment termination and 3-4 months after last dose of trastuzumab emtansine. Each cycle is 21 days.
Anti-trastuzumab Antibody (ATA)Day 1 on Cycles 1, and 4, at study treatment termination and 3-4 months after last dose of trastuzumab emtansine. Each cycle is 21 days.

Trial Locations

Locations (293)

Kaiser Permanente - Vallejo

🇺🇸

Vallejo, California, United States

The Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

Kaiser Permanente - San Diego

🇺🇸

San Diego, California, United States

Policlinico Universitario Campus Biomedico; Uoc Oncologia Medica

🇮🇹

Roma, Lazio, Italy

Taichung Veterans General Hospital; Dept of Surgery

🇨🇳

Taichung, Taiwan

Rocky Mountain Cancer Centers - Colorado Springs (Circle)

🇺🇸

Lone Tree, Colorado, United States

New England Cancer Specialists

🇺🇸

Scarborough, Maine, United States

Sint Augustinus Wilrijk

🇧🇪

Wilrijk, Belgium

Cliniques Universitaires St-Luc

🇧🇪

Bruxelles, Belgium

Instituto Nacional de Cancer - INCa; Oncologia

🇧🇷

Rio de Janeiro, RJ, Brazil

Hospital de Cancer de Barretos

🇧🇷

Barretos, São Paulo, Brazil

Tom Baker Cancer Centre; Dept of Medicine

🇨🇦

Calgary, Alberta, Canada

BC Cancer ? Surrey

🇨🇦

Surrey, British Columbia, Canada

Guangdong General Hospital

🇨🇳

Guangzhou, China

The Ottawa Hospital; Division of Infectious Diseases

🇨🇦

Ottawa, Ontario, Canada

London Regional Cancer Centre

🇨🇦

London, Ontario, Canada

CSSS champlain - Charles-Le Moyne

🇨🇦

Greenfield Park, Quebec, Canada

Princess Margaret Cancer Center

🇨🇦

Toronto, Ontario, Canada

Hopital du Saint Sacrement

🇨🇦

Quebec City, Quebec, Canada

Harbin Medical University Cancer Hospital

🇨🇳

Harbin, China

Sun Yet-sen University Cancer Center

🇨🇳

Guangzhou, China

Shandong Cancer Hospital

🇨🇳

Jinan, China

Clinica del Country

🇨🇴

Bogota, Colombia

Fudan University Shanghai Cancer Center

🇨🇳

Shanghai City, China

Fakultni Nemocnice Hradec Kralove; Dept of Radiotherapy & Oncology

🇨🇿

Hradec Kralove, Czechia

Institut Sainte Catherine;Recherche Clinique

🇫🇷

Avignon, France

HOPITAL JEAN MINJOZ; Oncologie

🇫🇷

Besancon, France

Centre Hospitalier Fleyriat; Oncologie/Hematologie

🇫🇷

Bourg En Bresse, France

Centre de Cancerologie de la Sarthe, Clinique Victor Hugo SoReCOH

🇫🇷

Le Mans, France

Centre Francois Baclesse; Comite Sein

🇫🇷

Caen, France

Institut Bergonie; Oncologie

🇫🇷

Bordeaux, France

Centre Jean Perrin; Oncologie

🇫🇷

Clermont Ferrand, France

Institut Paoli Calmettes; Oncologie Medicale

🇫🇷

Marseille, France

Institut Curie; Oncologie Medicale

🇫🇷

Paris, France

Hopital Saint Louis; Oncologie Medicale

🇫🇷

Paris, France

HOPITAL TENON; Cancerologie Medicale

🇫🇷

Paris, France

Centre Rene Huguenin; CONSULT SPECIALISEES

🇫🇷

St Cloud, France

HELIOS Klinikum Berlin-Buch; Klinik für Gynäkologie und Geburtshilfe

🇩🇪

Berlin, Germany

St. Johannes-Hospital

🇩🇪

Dortmund, Germany

Klinikum Sindelfingen-Böblingen; Frauenklinik

🇩🇪

Böblingen, Germany

Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum

🇩🇪

Essen, Germany

Klinik Johann Wolfgang von Goethe Uni; Klinik für Frauenheilkunde und Geburtshilfe

🇩🇪

Frankfurt, Germany

Universitätsklinikum Greifswald; Klinik für Frauenheilkunde und Brustzentrum

🇩🇪

Greifswald, Germany

MVZ Onko Medical GmbH Hannover, Ralf Lohse (Geschäftsführer)

🇩🇪

Hannover, Germany

St. Barbara-Klinik Hamm-Heessen GmbH; Frauenklinik

🇩🇪

Hamm, Germany

Medizinische Hochschule Hannover, Klinik für Frauenheilkunde und Geburtshilfe

🇩🇪

Hannover, Germany

St. Elisabeth Krankenhaus Köln GmbH; Gynäkologie und Geburtshilfe

🇩🇪

Koeln, Germany

Klinikum der Universität München; Frauenklinik - Onkologie II

🇩🇪

München, Germany

Oncologianova GmbH - Gesellschaft für Innovationen in der Onkologie

🇩🇪

Recklinghausen, Germany

St. Vincenz-Krankenhaus Paderborn; Haus 3 Frauenklinik

🇩🇪

Paderborn, Germany

Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe

🇩🇪

Offenbach, Germany

Universitätsfrauen- und Poliklinik am Klinikum Suedstadt

🇩🇪

Rostock, Germany

Gynäkologie Kompetenzzentrum; Praxis Dr. med. Carsten Hielscher

🇩🇪

Stralsund, Germany

Robert-Bosch-Krankenhaus; Brustzentrum

🇩🇪

Stuttgart, Germany

Gemeinschaftspraxis Dr. Kronawitter und Dr. Jung

🇩🇪

Traunstein, Germany

Univ General Hosp Heraklion; Medical Oncology

🇬🇷

Heraklion, Greece

Centro Oncológico Sixtino / Centro Oncológico SA

🇬🇹

Guatemala, Guatemala

St Vincent'S Uni Hospital; Medical Oncology

🇮🇪

Dublin, Ireland

Shaare Zedek Medical Center; Oncology Dept

🇮🇱

Jerusalem, Israel

University Hospital Limerick - Oncology

🇮🇪

Limerick, Ireland

Soroka Medical Center

🇮🇱

Beer Sheva, Israel

Sheba Medical Center; Tel Hashomer

🇮🇱

Ramat Gan, Israel

Istituto Nazionale Tumori Fondazione G. Pascale

🇮🇹

Napoli, Campania, Italy

Ausl Di Bologna-Ospedale Bellaria;U.O. Oncologia Medica

🇮🇹

Bologna, Emilia-Romagna, Italy

Università degli Studi Federico II; Clinica di Oncologia Medica

🇮🇹

Napoli, Campania, Italy

Policlinico S.Orsola-Malpighi; Istituto Oncologia R. Addarii

🇮🇹

Bologna, Emilia-Romagna, Italy

Az. Osp. Sant'Andrea; Oncologia Medica

🇮🇹

Roma, Lazio, Italy

ASST DI CREMONA; Unità di Patologia Mammaria Senologia e Breast Unit

🇮🇹

Cremona, Lombardia, Italy

Asst Papa Giovanni XXIII; Oncologia Medica

🇮🇹

Bergamo, Lombardia, Italy

Irccs Ospedale San Raffaele;Oncologia Medica

🇮🇹

Milano, Lombardia, Italy

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1

🇮🇹

Milano, Lombardia, Italy

Istituto Europeo Di Oncologia

🇮🇹

Milano, Lombardia, Italy

ASST DI MONZA; Oncologia Medica

🇮🇹

Monza, Lombardia, Italy

Azienda usl 5 Di Pisa-Ospedale Di Pontedera;U.O. Oncologia

🇮🇹

Pontedera, Toscana, Italy

Ospedale Antonio Perrino; Oncologia Medica

🇮🇹

Brindisi, Puglia, Italy

A.O.U.I. VERONA-OSPEDALE BORGO TRENTO; ONCOLODIA MEDICA-d.O.

🇮🇹

Verona, Veneto, Italy

Fondazione Del Piemonte Per L'oncologia IRCC Di Candiolo

🇮🇹

Candiolo, Piemonte, Italy

Hospital Angeles Metropolitano; Room 220

🇲🇽

Mexico City, Mexico CITY (federal District), Mexico

Oaxaca Site Management Organization

🇲🇽

Oaxaca de Juárez, Oaxaca, Mexico

The Panama Clinic

🇵🇦

Panama, Panama

Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion

🇵🇪

Bellavista, Peru

Centro Medico Monte Carmelo

🇵🇪

Arequipa, Peru

Clinica San Borja

🇵🇪

Lima, Peru

Hospital Nacional Guillermo Almenara Irigoyen; Oncology

🇵🇪

Lima, Peru

Institute for Oncology and Radiology of Serbia; Clinic for Medical Oncology

🇷🇸

Belgrade, Serbia

Hopelands Cancer Centre

🇿🇦

Hilton, South Africa

Medical Oncology Centre of Rosebank; Oncology

🇿🇦

Johannesburg, South Africa

Cancercare

🇿🇦

Port Elizabeth, South Africa

Private Oncology Centre

🇿🇦

Pretoria, South Africa

Hospital de Donostia; Servicio de Oncologia Medica

🇪🇸

San Sebastian, Guipuzcoa, Spain

Hospital Clínic i Provincial; Servicio de Oncología

🇪🇸

Barcelona, Spain

Hospital Universitari Sant Joan de Reus; Servicio de Oncologia

🇪🇸

Reus, Tarragona, Spain

Hospital Universitario La Paz; Servicio de Oncologia

🇪🇸

Madrid, Spain

HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia

🇪🇸

Madrid, Spain

Hospital Clinico Universitario de Salamanca; Servicio de Oncologia

🇪🇸

Salamanca, Spain

Skånes University Hospital, Skånes Department of Onclology

🇸🇪

Lund, Sweden

Hospital Universitario Dr. Peset; Servicio de Oncologia

🇪🇸

Valencia, Spain

Instituto Valenciano Oncologia; Oncologia Medica

🇪🇸

Valencia, Spain

Brust-Zentrum Zürich AG Seefeldstrasse 214 Zürich

🇨🇭

Zürich, Switzerland

Karolinska Hospital; Oncology - Radiumhemmet

🇸🇪

Stockholm, Sweden

VETERANS GENERAL HOSPITAL; Department of General Surgery

🇨🇳

Taipei, Taiwan

Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology

🇨🇳

Taipei City, Taiwan

Uludag Uni Hospital; Oncology

🇹🇷

Bursa, Turkey

Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department

🇹🇷

Edirne, Turkey

Inonu University Medical Faculty Turgut Ozal Medical Center Medical Oncology Department

🇹🇷

Malatya, Turkey

Ege Uni Medical Faculty Hospital; Oncology Dept

🇹🇷

Izmir, Turkey

Bristol Haematology and Oncology centre

🇬🇧

Bristol, United Kingdom

Royal Cornwall Hospital; Dept of Clinical Oncology

🇬🇧

Cornwall, United Kingdom

Castle Hill Hospital; The Queens Centre for Oncology and Haematology

🇬🇧

Cottingham, United Kingdom

North Devon District Hospital

🇬🇧

Devon, United Kingdom

Ninewells Hospital; Cancer Medicine

🇬🇧

Dundee, United Kingdom

Huddersfield Royal Infirmary

🇬🇧

Huddersfield, United Kingdom

St Thomas Hospital; Medicine Div.

🇬🇧

London, United Kingdom

Charing Cross Hospital; Medical Oncology.

🇬🇧

London, United Kingdom

Nottingham City Hospital; Oncology

🇬🇧

Nottingham, United Kingdom

Christie Hospital Nhs Trust; Medical Oncology

🇬🇧

Manchester, United Kingdom

Hartford Hospital

🇺🇸

Hartford, Connecticut, United States

Providence Alaska Medical Center

🇺🇸

Anchorage, Alaska, United States

Todd Cancer Institute at Long Beach Memorial Medical Center

🇺🇸

Long Beach, California, United States

Chao Family Comprehensive Cancer Center; UC Irvine Medical Center

🇺🇸

Orange, California, United States

Stanford University Medical Center

🇺🇸

Palo Alto, California, United States

Breastlink Medical Group Inc

🇺🇸

Santa Ana, California, United States

Washington Cancer Institute; Washington Hospital Center

🇺🇸

Washington, District of Columbia, United States

Rush University Medical Center

🇺🇸

Chicago, Illinois, United States

Edward Cancer Center Naperville

🇺🇸

Naperville, Illinois, United States

Edward Cancer Center Plainfield

🇺🇸

Plainfield, Illinois, United States

Cancer Care of Maine

🇺🇸

Brewer, Maine, United States

Mercy Medical Center; Medical Oncology & Hematology

🇺🇸

Baltimore, Maryland, United States

Greater Baltimore Medical Center

🇺🇸

Baltimore, Maryland, United States

Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Med Star Franklin Square Medical Center/Weinburg Cancer Institute

🇺🇸

Baltimore, Maryland, United States

Spectrum Health Hospitals

🇺🇸

Grand Rapids, Michigan, United States

Breslin Cancer Center

🇺🇸

Lansing, Michigan, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

William Beaumont Hospital

🇺🇸

Royal Oak, Michigan, United States

Sparta Cancer Center

🇺🇸

Sparta, New Jersey, United States

Carolinas Medical Center

🇺🇸

Charlotte, North Carolina, United States

Troy Cancer Treatment Program

🇺🇸

Troy, New York, United States

Batte Cancer Center - Carolinas Medical Center

🇺🇸

Concord, North Carolina, United States

Aultman Hospital; Aultman Hospital Cancer Center

🇺🇸

Canton, Ohio, United States

Fairview Hospital; Cleveland Clinic Cancer Center

🇺🇸

Cleveland, Ohio, United States

Kimmel Cancer Center Thomas Jefferson University

🇺🇸

Philadelphia, Pennsylvania, United States

Ohio State University, Arthur James Cancer Hospital

🇺🇸

Columbus, Ohio, United States

Lake Health/University Hospitals - Mentor Campus

🇺🇸

Mentor, Ohio, United States

Allegheny Cancer Center

🇺🇸

Pittsburgh, Pennsylvania, United States

York Hospital

🇺🇸

York, Pennsylvania, United States

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

Houston Methodist Hospital Outpatient Center

🇺🇸

Houston, Texas, United States

Hematology Oncology Associates of Fredericksburg, Inc.

🇺🇸

Fredericksburg, Virginia, United States

Uni of Texas - Md Anderson Cancer Center; Dept of Breast Medical Oncology

🇺🇸

Houston, Texas, United States

Joe Arrington Cancer Research & Treatment Center

🇺🇸

Lubbock, Texas, United States

Lynchburg Hem Onc Clinic Inc

🇺🇸

Lynchburg, Virginia, United States

Swedish Cancer Institute - Issaquah

🇺🇸

Issaquah, Washington, United States

PeaceHealth St. John Medical Center - Lower Columbia Cancer Center

🇺🇸

Longview, Washington, United States

Marshfield Clinic

🇺🇸

Marshfield, Wisconsin, United States

Centro Oncologico Riojano Integral (CORI)

🇦🇷

La Rioja, Argentina

Fundación CENIT para la Investigación en Neurociencias

🇦🇷

Buenos Aires, Argentina

Tiroler Landeskrankenanstalten Ges.M.B.H.; Abt. Für Gynäkologie

🇦🇹

Innsbruck, Austria

Medizinische Universität Wien; Univ.Klinik für Frauenheilkunde - Klinik für Gynäkologie

🇦🇹

Wien, Austria

Lkh Salzburg - Univ. Klinikum Salzburg; Iii. Medizinische Abt.

🇦🇹

Salzburg, Austria

Instituto de Oncología de Rosario

🇦🇷

Rosario, Argentina

Medizinische Universität Wien; Univ.Klinik für Innere Medizin I - Abt. für Onkologie

🇦🇹

Wien, Austria

AZ Sint Lucas (Sint Lucas)

🇧🇪

Gent, Belgium

CHU Sart-Tilman

🇧🇪

Liège, Belgium

Hospital Nossa Senhora da Conceicao

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Hospital Perola Byington

🇧🇷

Sao Paulo, São Paulo, Brazil

British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre

🇨🇦

Vancouver, British Columbia, Canada

Centre Hospitalier de l?Université de Montréal (CHUM)

🇨🇦

Montreal, Quebec, Canada

Jewish General Hospital

🇨🇦

Montreal, Quebec, Canada

McGill University Health Centre - Glen Site

🇨🇦

Montreal, Quebec, Canada

the First Hospital of Jilin University

🇨🇳

Changchun, China

Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)

🇨🇳

Shanghai, China

Oncomedica S.A.

🇨🇴

Monteria, Colombia

Vseobecna fakultni nemocnice v Praze

🇨🇿

Praha 2, Czechia

Fakultni nemocnice Olomouc; Onkologicka klinika

🇨🇿

Olomouc, Czechia

Hospital Pablo Tobon Uribe

🇨🇴

Medellin, Colombia

Centre Val Aurelle Paul Lamarque; Recherche Clinique

🇫🇷

Montpellier, France

Centre Henri Becquerel; Oncologie Medicale

🇫🇷

Rouen, France

Centre Paul Strauss; Oncologie Medicale

🇫🇷

Strasbourg, France

Hämatologie Onkologie im Zentrum MVZ GmbH

🇩🇪

Augsburg, Germany

Institut Gustave Roussy; Departement Oncologie Medicale

🇫🇷

Villejuif, France

Praxisklinik Krebsheilkunde für Frauen / Brustzentrum (Dres. Kittel/Klare)

🇩🇪

Berlin, Germany

Onkologische Schwerpunktpraxis Kurfürstendamm

🇩🇪

Berlin, Germany

Studienzentrum Berlin City

🇩🇪

Berlin, Germany

Onkologische Schwerpunktpraxis Bielefeld

🇩🇪

Bielefeld, Germany

Luisenkrankenhaus GmbH & Co. KG., Brustzentrum

🇩🇪

Düsseldorf, Germany

Universitätsklinikum Essen; Zentrum Für Frauenheilkunde

🇩🇪

Essen, Germany

Universitätsklinikum Erlangen; Frauenklinik

🇩🇪

Erlangen, Germany

Klinikum Esslingen; Klinik für Frauenheilkunde und Geburtshilfe

🇩🇪

Esslingen, Germany

Hämatologisch-Onkologische Gemeinschaftspraxis am Bethanien-Krankenhaus

🇩🇪

Frankfurt am Main, Germany

Evangelische Kliniken Gelsenkirchen GmbH; Brustzentrum

🇩🇪

Gelsenkirchen, Germany

Universitätsklinikum Freiburg; Frauenklinik

🇩🇪

Freiburg, Germany

Krankenhaus St. Elisabeth und St. Barbara, Klinik für Frauenheilkunde und Geburtshilfe

🇩🇪

Halle, Germany

Kooperatives Mammazentrum Hamburg Krankenhaus Jerusalem

🇩🇪

Hamburg, Germany

Diakovere Henriettenstift, Frauenklinik

🇩🇪

Hannover, Germany

Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg

🇩🇪

Heidelberg, Germany

Elisabeth-Krankenhaus Brustzentrum

🇩🇪

Kassel, Germany

Klinikum Kassel GmbH; Klinik für Frauenheilkunde und Geburtshilfe

🇩🇪

Kassel, Germany

UNI-Klinikum Campus Kiel Klinik für Gynäkologie und Geburtshilfe

🇩🇪

Kiel, Germany

Kliniken der Stadt Köln gGmbH Krankenhaus Holweide; Brustzentrum

🇩🇪

Köln, Germany

Gemeinschaftspraxis für Hämatologie und Onkologie, PD Dr. Bauer, Dr. Thiel

🇩🇪

Lebach, Germany

Medizinisches Zentrum für Hämatologie und Onkologie

🇩🇪

München, Germany

MVZ Nordhausen gGmbH, Praxis Dr. Grafe

🇩🇪

Nordhausen, Germany

Klinikum am Steinenberg Frauenklinik

🇩🇪

Reutlingen, Germany

HELIOS Dr. Horst Schmidt Kliniken Wiesbaden; Klinik für Gynäkologie und gynäkologische Onkologie

🇩🇪

Wiesbaden, Germany

Universitätsklinik Tübingen; Frauenklinik

🇩🇪

Tübingen, Germany

Universitätsklinikum Ulm Am Michelsberg; Frauenklinik

🇩🇪

Ulm, Germany

Marien-Hospital Witten; Frauenklinik Brustzentrum

🇩🇪

Witten, Germany

Grupo Angeles

🇬🇹

Guatemala City, Guatemala

Hämatologisch-Onkologische Schwerpunktpraxis Dres. Schlag & Schöttker

🇩🇪

Würzburg, Germany

Cork Uni Hospital; Oncology Dept

🇮🇪

Cork, Ireland

Galway Uni Hospital; Oncology Dept

🇮🇪

Galway, Ireland

Hadassah University Hospital - Ein Kerem

🇮🇱

Jerusalem, Israel

Kaplan Medical Center; Oncology Inst.

🇮🇱

Rehovot, Israel

Rabin MC; Davidof Center - Oncology Institute

🇮🇱

Petach Tikva, Israel

Azlenda Ospendaliero-Universitaria Pisana; C.O. Oncologia 2

🇮🇹

Pisa, Toscana, Italy

IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II

🇮🇹

Padova, Veneto, Italy

Médicos Especialistas en Cáncer SC

🇲🇽

Aguascalientes, Mexico

Centro Oncologico America

🇵🇦

Panama, Panama

Instituto Nacional de Cancerologia; Oncology

🇲🇽

Mexico City, Mexico

Oncology Institute of Vojvodina

🇷🇸

Sremska Kamenica, Serbia

Cape Town Oncology Trials

🇿🇦

Cape Town, South Africa

Wits Donald Gordon Clinical Trial Centre; Medical Oncology

🇿🇦

Johannesburg, South Africa

Complexo Hospitalario de Vigo. Hospital Álvaro Cunqueiro; Servicio de Oncología

🇪🇸

Vigo, Pontevedra, Spain

Hospital Severo Ochoa; Servicio de Oncologia

🇪🇸

Leganes, Madrid, Spain

Hospital Regional Universitario Carlos Haya; Servicio de Oncologia

🇪🇸

Malaga, Spain

Gävle Sjukhus; Onkologiska Kliniken

🇸🇪

Gävle, Sweden

Hospital Universitario Virgen del Rocio; Servicio de Oncologia

🇪🇸

Sevilla, Spain

Hospital de Navarra; Servicio de Oncologia

🇪🇸

Navarra, Spain

Kantonsspital Aarau AG Medizin Onkologie; ZENTRUM FÜR ONKOLOGIE, HÄMATOLOGIE & TRANSFUSIONSMEDIZIN

🇨🇭

Aarau, Switzerland

National Taiwan Uni Hospital; General Surgery

🇨🇳

Taipei, Taiwan

Kartal Dr Lutfi Kirdar Sehir Hastanesi; Medical Oncology Department

🇹🇷

Istanbul, Turkey

University Hospital Birmingham The Cancer Centre, Queen Elizabeth Hospital

🇬🇧

Birmingham, United Kingdom

Bradford Royal Infirmary; Dept of Medical Oncology C/O Ward15

🇬🇧

Bradford, United Kingdom

Weston Park Hospital

🇬🇧

Sheffield, United Kingdom

Leeds Teaching Hosp NHS Trust;St James's Institute of Onc

🇬🇧

Leeds, United Kingdom

US oncology research at Minnesota Oncology

🇺🇸

Saint Louis Park, Minnesota, United States

Mount Sinai Medical Center

🇺🇸

Miami Beach, Florida, United States

Uni of Pittsburgh; Magee-Women'S Hospital

🇺🇸

Pittsburgh, Pennsylvania, United States

Avera Cancer Institute

🇺🇸

Sioux Falls, South Dakota, United States

Sanford Roger Maris Cancer Center

🇺🇸

Fargo, North Dakota, United States

Thompson Cancer Survival Center

🇺🇸

Knoxville, Tennessee, United States

Cancer Care Northwest

🇺🇸

Spokane, Washington, United States

Universitätsklinikum Halle (Saale); Universitätsklinik Und Poliklinik Für Gynäkologie

🇩🇪

Halle, Germany

Mater Misericordiae Uni Hospital; Oncology

🇮🇪

Dublin, Ireland

Euromedical General Clinic of Thessaloniki; Oncology Department

🇬🇷

Thessaloniki, Greece

Beaumont Hospital; Cancer Clinical Trials Unit

🇮🇪

Dublin, Ireland

Nstituto Nacional de Ciancias Medicas Y Nutricion, Salvador Zubir

🇲🇽

Mexico City, Mexico CITY (federal District), Mexico

Hospital Nacional Carlos Alberto Seguin Escobedo-Essalud; Oncology & Haemathology

🇵🇪

Arequipa, Peru

Chang Gung Medical Foundation - Linkou; Dept of Surgery

🇨🇳

Taoyuan, Taiwan

IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A

🇮🇹

Genova, Liguria, Italy

Colorado Cancer Research Program/Admin

🇺🇸

Denver, Colorado, United States

Kaiser Permanente - Franklin

🇺🇸

Denver, Colorado, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

UF Health Orlando

🇺🇸

Orlando, Florida, United States

Columbia River Oncology Program

🇺🇸

Portland, Oregon, United States

Medical University of South Carolina; Hollings Cancer Center

🇺🇸

Charleston, South Carolina, United States

Norton Healthcare Inc.

🇺🇸

Louisville, Kentucky, United States

Virginia Commonwealth University - Massey Cancer Center

🇺🇸

Richmond, Virginia, United States

University of Florida; Davis Cancer Pavilion and Shands Medical Plaza

🇺🇸

Gainesville, Florida, United States

University of Kentucky Medical Center

🇺🇸

Lexington, Kentucky, United States

Cross Cancer Institute ; Dept of Medical Oncology

🇨🇦

Edmonton, Alberta, Canada

Hospital Sao Jose

🇧🇷

Sao Paulo, SP, Brazil

Columbia University Medical Center

🇺🇸

New York, New York, United States

Rutgers Cancer Institute of New Jersey

🇺🇸

New Brunswick, New Jersey, United States

Yale Cancer Center

🇺🇸

New Haven, Connecticut, United States

Centra Alan B. Pearson Regional Cancer Center

🇺🇸

Lynchburg, Virginia, United States

University of Iowa

🇺🇸

Iowa City, Iowa, United States

Iop Instituto de Oncologia Do Parana

🇧🇷

Curitiba, Paraná, Brazil

Clinicas Oncologicas Integradas - COI

🇧🇷

Rio De Janeiro, Brazil

UPCO - Unidade de Pesquisas Clínicas em Oncologia

🇧🇷

Pelotas, Rio Grande Do Sul, Brazil

Hospital Moinhos de Vento

🇧🇷

Porto Alegre, Rio Grande Do Sul, Brazil

Instituto de Ensino e Pesquisa Sao Lucas - IEP

🇧🇷

Sao Paulo, São Paulo, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

🇧🇷

Sao Paulo, São Paulo, Brazil

Chao Family Comprehensive Cancer Center

🇺🇸

Orange, California, United States

Washington Cancer Institute

🇺🇸

Washington, District of Columbia, United States

University of Florida

🇺🇸

Gainesville, Florida, United States

Mercy Medical Center

🇺🇸

Baltimore, Maryland, United States

Aultman Hospital

🇺🇸

Canton, Ohio, United States

Fairview Hospital

🇺🇸

Cleveland, Ohio, United States

Uni of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

Uni of Texas - Md Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Tiroler Landeskrankenanstalten Ges.M.B.H.

🇦🇹

Innsbruck, Austria

Lkh Salzburg - Univ. Klinikum Salzburg

🇦🇹

Salzburg, Austria

Medizinische Universität Wien

🇦🇹

Wien, Austria

Instituto Nacional de Cancer - INCa

🇧🇷

Rio de Janeiro, Brazil

Arthur J.E. Child Comprehensive Cancer Center

🇨🇦

Calgary, Alberta, Canada

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

The Ottawa Hospital

🇨🇦

Ottawa, Ontario, Canada

Queen Mary Hospital; Surgery

🇭🇰

Hong Kong, Hong Kong

Tuen Mun Hospital; Clinical Oncology

🇭🇰

Hong Kong, Hong Kong

Pamela Youde Nethersole Eastern Hospital; Clinical Oncology

🇭🇰

Hong Kong, Hong Kong

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