MedPath

A Study to Compare Subcutaneous (SC) Versus Intravenous (IV) Administration of Herceptin (Trastuzumab) in Women With Human Epidermal Growth Factor Receptor (HER) 2-Positive Early Breast Cancer

Registration Number
NCT00950300
Lead Sponsor
Hoffmann-La Roche
Brief Summary

In this open-label multicenter trial, participants with operable or locally advanced breast cancer will be randomized to pre-operative treatment with 8 cycles of chemotherapy (4 cycles of docetaxel followed by 4 cycles of 5-fluorouracil, epirubicin, and cyclophosphamide) concurrent with either SC Herceptin or IV Herceptin. After surgery, participants will receive a further 10 cycles of SC or IV Herceptin as per randomization to complete 1 year of treatment. All cycles will be 21 days in length. After the end of study treatment, participants will be followed for safety and efficacy for up to 5 years or until disease recurrence, whichever is earlier.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
596
Inclusion Criteria
  • Adult women greater than or equal to (≥) 18 years of age
  • Non-metastatic primary invasive adenocarcinoma of the breast clinical stage I to IIIC, including inflammatory and multicentric/multifocal breast cancer, with tumor size ≥1 centimeter (cm) by ultrasound or ≥2 cm by palpation, centrally confirmed HER2-positive (immunohistochemical score [IHC] 3+ or in situ hybridization [ISH]-positive)
  • At least 1 measurable lesion in breast or lymph nodes (≥1 cm by ultrasound or ≥2 cm by palpation), except for inflammatory carcinoma (T4d)
  • Baseline left ventricular ejection fraction (LVEF) ≥55%
  • Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
  • Adequate organ function at Baseline
Exclusion Criteria
  • History of any prior (ipsilateral and/or contralateral) invasive breast carcinoma
  • Past or current history of malignant neoplasms, except for curatively treated basal and squamous cell carcinoma of the skin and in situ carcinoma of the cervix
  • Metastatic disease
  • Any prior therapy with anthracyclines
  • Prior anti-HER2 therapy or biologic or immunotherapy
  • Serious cardiac illness
  • Pregnant or lactating women

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Herceptin SC + ChemotherapyHerceptin SC [trastuzumab]Participants will receive Herceptin via SC injection for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin SC will be given on Day 1 of each 21-day cycle, as a 600-milligram (mg) fixed dose.
Herceptin IV + ChemotherapyHerceptin IV [trastuzumab]Participants will receive Herceptin via IV infusion for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin IV will be given on Day 1 of each 21-day cycle, as 8 milligrams per kilogram (mg/kg) for a loading dose during Cycle 1 and as 6 mg/kg during subsequent cycles.
Herceptin IV + Chemotherapy5-FluorouracilParticipants will receive Herceptin via IV infusion for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin IV will be given on Day 1 of each 21-day cycle, as 8 milligrams per kilogram (mg/kg) for a loading dose during Cycle 1 and as 6 mg/kg during subsequent cycles.
Herceptin IV + ChemotherapyCyclophosphamideParticipants will receive Herceptin via IV infusion for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin IV will be given on Day 1 of each 21-day cycle, as 8 milligrams per kilogram (mg/kg) for a loading dose during Cycle 1 and as 6 mg/kg during subsequent cycles.
Herceptin IV + ChemotherapyDocetaxelParticipants will receive Herceptin via IV infusion for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin IV will be given on Day 1 of each 21-day cycle, as 8 milligrams per kilogram (mg/kg) for a loading dose during Cycle 1 and as 6 mg/kg during subsequent cycles.
Herceptin IV + ChemotherapyEpirubicinParticipants will receive Herceptin via IV infusion for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin IV will be given on Day 1 of each 21-day cycle, as 8 milligrams per kilogram (mg/kg) for a loading dose during Cycle 1 and as 6 mg/kg during subsequent cycles.
Herceptin SC + Chemotherapy5-FluorouracilParticipants will receive Herceptin via SC injection for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin SC will be given on Day 1 of each 21-day cycle, as a 600-milligram (mg) fixed dose.
Herceptin SC + ChemotherapyCyclophosphamideParticipants will receive Herceptin via SC injection for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin SC will be given on Day 1 of each 21-day cycle, as a 600-milligram (mg) fixed dose.
Herceptin SC + ChemotherapyDocetaxelParticipants will receive Herceptin via SC injection for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin SC will be given on Day 1 of each 21-day cycle, as a 600-milligram (mg) fixed dose.
Herceptin SC + ChemotherapyEpirubicinParticipants will receive Herceptin via SC injection for 8 cycles prior to surgery and an additional 10 cycles after surgery. Docetaxel will be co-administered during Cycles 1 to 4; chemotherapy during Cycles 5 to 8 will include 5-fluorouracil, cyclophosphamide, and epirubicin. Herceptin SC will be given on Day 1 of each 21-day cycle, as a 600-milligram (mg) fixed dose.
Primary Outcome Measures
NameTimeMethod
Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to SurgeryPre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)

Pre-dose samples were obtained prior to surgery (Cycle 8). The observed Ctrough was recorded, averaged among all participants, and expressed in micrograms per milliliter (μg/mL).

Percentage of Participants With Pathological Complete Response (pCR)After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)

Participants were evaluated following eight cycles of treatment and after surgery to assess for pCR, defined as absence of neoplastic invasive cells in the breast according to pathologist examination. The percentage of participants with pCR was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.

Secondary Outcome Measures
NameTimeMethod
Number of Participants With Ctrough of Trastuzumab >20 μg/mL Prior to SurgeryPre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)

Pre-dose samples were obtained prior to surgery (Cycle 8). The number of participants who had an observed Ctrough \>20 μg/mL was reported.

Number of Participants With Ctrough of Trastuzumab >20 μg/mL After SurgeryPre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)

Pre-dose samples were obtained after surgery (Cycle 13). The number of participants who had an observed Ctrough \>20 μg/mL was reported.

Maximum Serum Concentration (Cmax) of Trastuzumab Prior to SurgeryPre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)

PK samples were obtained prior to surgery (Cycle 7). The Cmax during Cycle 7 was recorded, averaged among all participants, and expressed in μg/mL.

Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to SurgeryPre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)

PK samples were obtained prior to surgery (Cycle 7). The Tmax during Cycle 7 was recorded, averaged among all participants, and expressed in days.

Observed Ctrough of Trastuzumab After SurgeryPre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)

Pre-dose samples were obtained after surgery (Cycle 13). The observed Ctrough was recorded, averaged among all participants, and expressed in μg/mL.

Predicted Ctrough of Trastuzumab Prior to SurgeryPre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)

Predicted Ctrough at pre-dose prior to surgery (Cycle 8) was determined on the basis of a population PK model from Study BP22023 (NCT00800436). The mean predicted Ctrough was expressed in μg/mL.

Predicted Ctrough of Trastuzumab After SurgeryPre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)

Predicted Ctrough at pre-dose after surgery (Cycle 13) was determined on the basis of a population PK model from Study BP22023 (NCT00800436). The mean predicted Ctrough was expressed in μg/mL.

Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0, Among Those With Measurable Disease at BaselineTumor assessments at Baseline; on Day 1 of Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months overall)

Tumor response was assessed using RECIST version 1.0. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to less than (\<) 10 millimeters (mm) with no prior assessment of progressive disease (PD). PR was defined as greater than or equal to (≥) 30% decrease from Baseline in sum diameter (SD) of target lesions with no prior assessment of PD. PD was defined as ≥20% relative increase and ≥5 mm of absolute increase in the SD of target lesions, taking as reference the smallest SD recorded since treatment started; or appearance of 1 or more new lesions. The percentage of participants with overall response of CR or PR at the end of neoadjuvant treatment was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.

Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to SurgeryPre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)

PK samples were obtained prior to surgery (Cycle 7). Values were extrapolated beyond Day 15 to produce the area over the full 21-day cycle. The AUC21d value at Cycle 7 was calculated from trastuzumab concentration-time profiles using standard non-compartmental PK methods, averaged among all participants, and expressed in days multiplied by micrograms per milliliters (d\*μg/mL).

Cmax of Trastuzumab After SurgeryPre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)

PK samples were obtained after surgery (Cycle 12). The Cmax during Cycle 12 was recorded, averaged among all participants, and expressed in μg/mL.

Tmax of Trastuzumab After SurgeryPre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)

PK samples were obtained after surgery (Cycle 12). The Tmax during Cycle 12 was recorded, averaged among all participants, and expressed in days.

AUC21d of Trastuzumab After SurgeryPre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)

PK samples were obtained after surgery (Cycle 12). Values were extrapolated beyond Day 15 to produce the area over the full 21-day cycle. The AUC21d value at Cycle 12 was calculated from trastuzumab concentration-time profiles using standard non-compartmental PK methods, averaged among all participants, and expressed in d\*μg/mL.

Percentage of Participants With Total Pathological Complete Response (tpCR)After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)

Participants were evaluated following eight cycles of treatment and after surgery to assess for tpCR, defined as absence of neoplastic invasive cells in the breast and axillary lymph nodes according to pathologist examination. The percentage of participants with tpCR was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method.

Time to Response According to RECIST Version 1.0, Among Those With Measurable Disease at BaselineTumor assessments at Baseline; on Day 1 Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of chemotherapy (approximately 6 months overall)

Tumor response was assessed using RECIST version 1.0. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to \<10 mm with no prior assessment of PD. PR was defined as ≥30% decrease from Baseline in SD of target lesions with no prior assessment of PD. PD was defined as ≥20% relative increase and ≥5 mm of absolute increase in the SD of target lesions, taking as reference the smallest SD recorded since treatment started; or appearance of 1 or more new lesions. Time to response was defined as the time from first dose of study medication to the first assessment of CR or PR, which was the date the response was first documented by objective evidence, among participants with an overall response of CR or PR.

Percentage of Participants Who Experienced a Protocol-Defined EventScreening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall)

Protocol-defined events included disease recurrence/progression (local, regional, distant, contralateral) or death from any cause. Imaging was performed at specified visits for up to 5 years after last dose. Thereafter, participants were followed for survival only. The percentage of participants who experienced a protocol-defined event at any time during the study was reported.

Event-Free Survival (EFS)Screening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall)

Protocol-defined events included disease recurrence or progression (local, regional, distant, contralateral) or death from any cause. Imaging was performed at specified visits for up to 5 years after last dose. Thereafter, participants were followed for survival only. EFS was estimated by Kaplan-Meier analysis and defined as the time from randomization to the first protocol-defined event.

Percentage of Participants Who DiedContinuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall)

The percentage of participants who died at any time during the study was reported.

Overall Survival (OS)Continuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall)

OS was estimated by Kaplan-Meier analysis and defined as the time from randomization to death from any cause.

Number of Participants With Anti-Drug Antibodies (ADAs) Against TrastuzumabBaseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18

Participants provided PK samples for evaluation of anti-trastuzumab antibodies. The number of participants with "Treatment-induced ADAs" and "Treatment-enhanced ADA" against trastuzumab at any time during or after treatment was reported. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result (four-fold increase of titer).

Number of Participants With ADAs Against Recombinant Human Hyaluronidase (rHuPH20)Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18

Participants in the Herceptin SC arm provided PK samples for evaluation of anti-rHuPH20 antibodies. The number of participants with "Treatment-induced ADAs" and "Treatment-enhanced ADA" against rHuPH20 (an excipient unique to the SC formulation) at any time during or after treatment was reported. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result (four-fold increase of titer).

Trial Locations

Locations (106)

Centro Medico San Roque; Oncology Dept

🇦🇷

Tucuman, Argentina

Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika

🇭🇺

Szeged, Hungary

Hospital Privado San Jose; Oncologia

🇲🇽

Obregon, Mexico

Chang Gung Medical Foundation-Taipei

🇨🇳

Taoyuan, Taiwan

Chulalongkorn Hospital; Medical Oncology

🇹🇭

Bangkok, Thailand

National Cancer Inst.

🇹🇭

Bangkok, Thailand

Phramongkutklao Hospital;Dept Surgery/Surgical Oncology Unit

🇹🇭

Bangkok, Thailand

Blokhin Cancer Research Center; Combined Treatment

🇷🇺

Moscow, Russian Federation

Moscow city oncology hospital #62 of Moscow Healthcare Department

🇷🇺

Moscow, Russian Federation

SBI of Healthcare Samara Regional Clinical Oncology Dispensary

🇷🇺

Samara, Russian Federation

Caipo; Oncology

🇦🇷

Tucuman, Argentina

Liga Norte Riograndense Contra O Câncer

🇧🇷

Natal, RN, Brazil

Hospital Sao Rafael - HSR

🇧🇷

Salvador, BA, Brazil

Hospital das Clinicas - UFPR; Quimioterapia

🇧🇷

Curitiba, PR, Brazil

Clinica de Neoplasias Litoral

🇧🇷

Itajai, SC, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

🇧🇷

Sao Paulo, SP, Brazil

Hospital Amaral Carvalho

🇧🇷

Jau, SP, Brazil

Hopital Albert Michallon; Oncologie

🇫🇷

La Tronche, France

Institut Daniel Hollard; Chimiotherapie Ambulatoire

🇫🇷

Grenoble, France

Praxis Dr. Schoenegg

🇩🇪

Berlin, Germany

Centre Jean Bernard

🇫🇷

Le Mans, France

Olsztyński Ośrodek Onkologiczny Kopernik sp. z o.o.

🇵🇱

Olsztyn, Poland

FSBI"National Medical Research Center of Oncology named after N.N.Petrov" MHRF

🇷🇺

St Petersburg, Leningrad, Russian Federation

Centrum Onkologii - Instytut im. Marii Skłodowskiej-Curie Klinika Nowotworów Piersi i Chirurgii

🇵🇱

Warszawa, Poland

Ivanovo Regional Oncology Dispensary

🇷🇺

Ivanovo, Russian Federation

SBI for HPE "Ryazan State Medical University n.a. I.P. Pavlov" of MoH of RF

🇷🇺

Ryazan, Russian Federation

Cancercare

🇿🇦

Cape Town, South Africa

Groote Schuur Hospital ( Uni of Capetown ); Oncology Dept

🇿🇦

Cape Town, South Africa

Wits Donald Gordon Clinical Trial Centre; Medical Oncology

🇿🇦

Parktown, Johannesburg, South Africa

Pretoria-East Hospital; 1 Sanwood Park

🇿🇦

Pretoria, South Africa

Rondebosch Oncology Centre

🇿🇦

Rondebosch, South Africa

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

🇪🇸

Madrid, Spain

Prince of Songkla Uni ; Unit of Medical Oncology

🇹🇭

Songkhla, Thailand

Istituto Nazionale Tumori Irccs Fondazione g. Pascale;s.c. Ematologia Oncologica

🇮🇹

Napoli, Campania, Italy

Fondazione Salvatore Maugeri; Servizio Di Prevenzione Oncologica

🇮🇹

Pavia, Lombardia, Italy

Fondazione Salvatore Maugeri

🇮🇹

Pavia, Lombardia, Italy

Fakultni nemocnice Olomouc; Onkologicka klinika

🇨🇿

Olomouc, Czechia

Lekarske Fakulty Univerzity Karlovy Fakultni Nemocnice Na Bulovce; Ustav Radiacni Onkologie

🇨🇿

Praha, Czechia

St. Johannes Hospital

🇩🇪

Dortmund, Germany

Hopital Maisonneuve- Rosemont; Oncology

🇨🇦

Montreal, Quebec, Canada

Grupo Salud Coop

🇨🇴

Bogota, Colombia

Oncólogos de Occidente

🇨🇴

Pereira, Colombia

HOPITAL JEAN MINJOZ; Oncologie

🇫🇷

Besancon, France

Hospital Perola Byington

🇧🇷

Sao Paulo, SP, Brazil

Instituto de Oncologia de Sorocaba - CEPOS

🇧🇷

Sorocaba, SP, Brazil

Hospital Universitario San Ignacio

🇨🇴

Bogota, Colombia

CHU de Québec - Hôpital du Saint-Sacrement / ONCOLOGY

🇨🇦

Quebec, Canada

Krajska Nemocnice Pardubice Neurologicka Klinika

🇨🇿

Pardubice, Czechia

Fakultni Thomayerova Nemocnice; Onkologicke Oddeleni

🇨🇿

Praha, Czechia

Tartu University Hospital; Clinic of Hematology and Oncology

🇪🇪

Tartu, Estonia

Institut Jean Godinot; Hopital De Jour

🇫🇷

Reims, France

CAMPUS CHARITÉ MITTE; Tagesklinik für Onkologie u.Hämatologie

🇩🇪

Berlin, Germany

Johanniter GmbH; Johanniter-Krankenhaus; Internistische Onkologie

🇩🇪

Bonn, Germany

North Estonia Medical Centre Foundation; Oncology Centre

🇪🇪

Tallinn, Estonia

Centre Rene Huguenin; Medecine B

🇫🇷

St Cloud, France

Hopital Saint Louis ; Service d Oncologie Medicale Fougere 6 (Pr Misset)

🇫🇷

Paris, France

Centro Oncologico S.A.

🇬🇹

Guatemala, Guatemala

Queen Mary Hospital; Surgery

🇭🇰

Hong Kong, Hong Kong

Hospital of Aladar Petz; Dept of Oncoradiology

🇭🇺

Gyor, Hungary

Rabin Medical Center; Oncology Dept

🇮🇱

Petach Tikva, Israel

Universitätsklinik Tübingen; Frauenklinik

🇩🇪

Tübingen, Germany

Semmelweis Egyetem Onkologiai Központ

🇭🇺

Budapest, Hungary

Sana Klinikum Offenbach GmbH; Klinik für Gynäkologie & Geburtshilfe

🇩🇪

Offenbach, Germany

Sankt Elisabeth Krankenhaus; Gynaekology

🇩🇪

Leipzig, Germany

Gynaekologisch-Onkologische Schwerpunktpraxis Prof. Dr. med. Lueck, Dr. Schrader und Dr. Noeding

🇩🇪

Hannover, Germany

Klinik Lippe Lemgo; Frauenklinik

🇩🇪

Lemgo, Germany

Klinik Obergöltzsch; Abt. Gynäkologie

🇩🇪

Rodewisch, Germany

Hadassah Ein Karem Hospital; Oncology Dept

🇮🇱

Jerusalem, Israel

ASST DI CREMONA; Dip. Medicina - S.C. Oncologia

🇮🇹

Cremona, Lombardia, Italy

Korea University Anam Hospital; Oncology Haemotology

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center, Uni Ulsan Collegemedicine; Dept.Internal Medicine / Divisionhematology/Oncology

🇰🇷

Seoul, Korea, Republic of

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

🇵🇪

Arequipa, Peru

Hospital Nacional Edgardo Rebagliati Martins; Oncologia

🇵🇪

Lima, Peru

Samsung Medical Centre; Division of Hematology/Oncology

🇰🇷

Seoul, Korea, Republic of

Gachon Medical School Gil Medical Center; Medical Oncology

🇰🇷

Incheon, Korea, Republic of

Oncosalud Sac; Oncología

🇵🇪

Lima, Peru

Wojewodzki Szpital Zespolony; Oddział Onkologii

🇵🇱

Elblag, Poland

Centro Oncológico Estatal; ISSSEMYM Oncología

🇲🇽

Toluca, Mexico

Centro Oncologico America

🇵🇦

Panama, Panama

Unidad de Investigacion Oncologia Clinica - Piura; Unidad de Oncología Clínica

🇵🇪

Piura, Peru

Clinica Ricardo Palma

🇵🇪

San Isidro, Peru

COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

🇵🇱

Lublin, Poland

State Budget Institution of Healthcare of Stavropol region Pyatigorsk Oncology Dispensary

🇷🇺

Pyatigorsk, Russian Federation

Saratov Regional Clinical Hospital & Pathology Centre

🇷🇺

Saratov, Russian Federation

Tula Regional Oncology Dispensary

🇷🇺

Tula, Russian Federation

Saint-Petersburg City Clinical Oncology Dispensary

🇷🇺

St Petersburg, Russian Federation

SBI of Healthcare of Stavropol region Stavropol Regional Clinical Oncology Dispensary

🇷🇺

Stavropol, Russian Federation

GUZ Vladimir Regional Clinical Oncological Dispensary

🇷🇺

Vladimir, Russian Federation

Vychodoslovensky onkologicky ustav

🇸🇰

Kosice, Slovakia

Nzz - Oncology Outpatient Clinic

🇸🇰

Poprad, Slovakia

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

🇪🇸

Valencia, Spain

National Hospital; Oncotherapy Dept

🇿🇦

Bloemfontein, South Africa

Hospital Universitari Sant Joan de Reus; Servicio de Oncologia

🇪🇸

Reus, Tarragona, Spain

Sandton Oncology Centre

🇿🇦

Sandton, South Africa

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

🇪🇸

Santiago de Compostela, LA Coruña, Spain

Skånes University Hospital, Skånes Department of Onclology

🇸🇪

Lund, Sweden

Hospital Universitario Miguel Servet; Servicio Oncologia

🇪🇸

Zaragoza, Spain

Changhua Christian Hospital; Dept of Surgery

🇨🇳

Changhua, Taiwan

Akademiska sjukhuset, Onkologkliniken

🇸🇪

Uppsala, Sweden

Taipei Veterans General Hospital

🇨🇳

Taipei City, Taiwan

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

🇨🇳

Taipei, Taiwan

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

🇹🇭

Bangkok, Thailand

Dokuz Eylul Uni Medical Faculty; Oncology Dept

🇹🇷

Izmir, Turkey

Akdeniz University Medical Faculty; Medical Oncology Department

🇹🇷

Antalya, Turkey

Istanbul Uni of Medicine Faculty; Oncology Dept

🇹🇷

Istanbul, Turkey

Hacettepe Uni Medical Faculty Hospital; Oncology Dept

🇹🇷

Sıhhiye, Ankara, Turkey

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