A Study of Ipatasertib in Combination With Paclitaxel as a Treatment for Participants With PIK3CA/AKT1/PTEN-Altered, Locally Advanced or Metastatic, Triple-Negative Breast Cancer or Hormone Receptor-Positive, HER2-Negative Breast Cancer
- Registration Number
- NCT03337724
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
This study will evaluate the efficacy of ipatasertib + paclitaxel versus placebo + paclitaxel in participants with histologically confirmed, locally advanced or metastatic triple-negative breast cancer (TNBC) and in participants with locally advanced or metastatic hormone receptor positive (HR+)/ human epidermal growth factor receptor 2 negative (HER2-) breast adenocarcinoma who are not suitable for endocrine therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 579
- Women or men aged =>18 years with histologically documented triple-negative breast cancer (TNBC) or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Adequate hematologic and organ function within 14 days prior to treatment initiation
- Histologically documented TNBC or HR+/HER2- adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to resection with curative intent
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Eligible for taxane monotherapy, as per local investigator assessment (e.g., absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control which may require combination chemotherapy)
- HR+/HER2- breast cancer that is not considered appropriate for endocrine-based therapy and meets one of the following: patient has recurrent disease <=5 years of being on adjuvant endocrine therapy or if patient with de novo metastatic disease have progressed within 6 months of being on first line endocrine therapy.
- Consent to submit a formalin-fixed, paraffin-embedded tumor (FFPE) tissue block or freshly cut unstained, serial tumor slides from the most recently collected tumor tissue for central molecular analysis
- Confirmation of biomarker eligibility using an appropriately validated molecular assay at a diagnostic laboratory, Clinically Laboratory Improvement Amendments (CLIA) or equivalently accredited i.e., valid results from either central testing or local testing of tumor tissue or blood demonstrating PIK3CA/AKT1/PTEN-altered status
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception and agreement to refrain from donating eggs
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods and agreement to refrain from donating sperm
- Treatment with approved or investigational cancer therapy within 14 days prior to treatment initiation
- Any previous chemotherapy for inoperable locally advanced or metastatic TNBC or HR+/HER2- adenocarcinoma of the breast (patients receiving neo/adjuvant chemotherapy eligible provided they have at least a 12 month disease-free interval)
- History of or known presence of brain or spinal cord metastases
- Malignancies other than breast cancer within 5 years prior to treatment initiation (except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or Stage I uterine cancer)
- Prior treatment with an Akt inhibitor (prior PI3K or mTOR inhibitors are allowed)
- History of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills
- Active infection requiring systemic anti-microbial treatment (including antibiotics, anti-fungals, and anti-viral agents)
- Known human immunodeficiency virus (HIV) infection
- Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, including active viral or other hepatitis, current drug or alcohol abuse, or cirrhosis
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of treatment (or anticipated need during study)
- Pregnant or breastfeeding, or intending to become pregnant during the study
- Clinically significant cardiac dysfunction (including NYHA Class II/III/IV heart failure, left ventricular ejection fraction [LVEF] <50%, active ventricular arrhythmia requiring medication, history of myocardial infarction within 6 months of treatment initiation, clinically significant electrocardiogram [ECG] abnormalities).
- Need for chronic corticosteroid therapy of >=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids or immunosuppressants for a chronic disease
- Unresolved, clinically significant toxicity from prior therapy, except for alopecia and Grade 1 peripheral neuropathy
- Uncontrolled clinical symptoms including pleural effusion, pericardial effusion, or ascites, tumor-related pain, hypercalcemia (or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy)
- History of Type I or Type II diabetes mellitus requiring insulin
- Grade >=2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
- History of or active inflammatory bowel disease or active bowel inflammation
- Clinically significant lung disease (including pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, active infection/ history of opportunistic infections)
- Treatment with strong CYP3A inhibitors or strong CYP3A inducers within 2 weeks or 5 drug-elimination half-lives, whichever is longer, prior to initiation of treatment
- Grade >=2 peripheral neuropathy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Paclitaxel Placebo - Ipatasertib + Paclitaxel Paclitaxel - Placebo + Paclitaxel Paclitaxel - Ipatasertib + Paclitaxel Ipatasertib -
- Primary Outcome Measures
Name Time Method Cohort A: Progression-Free Survival (PFS) From randomization up to 27 months PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1), or death from any cause, whichever occurred first, assessed up to 27 months for this outcome measure. Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). The appearance of one or more new lesions was also considered progression.
Cohort B: PFS From randomization up to 24.4 months PFS was defined as the time from randomization to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 24.4 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Abbreviation used in statistical analysis: PI3K=phosphoinositide 3-kinase and mTOR=mammalian target of rapamycin inhibitor.
Cohort C: PFS From enrollment up to 31 months PFS for Cohort C was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
- Secondary Outcome Measures
Name Time Method Cohort C: CBR From enrollment up to 31 months CBR was defined as percentage of participants with an objective response (CR or PR), or SD for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1 assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
Cohort A and B: Clinical Benefit Rate (CBR) From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B CBR was defined as percentage of participants with an objective response (CR or PR), or stable disease (SD) for at least 24 weeks, as determined by the investigator through the use of RECIST v.1.1. assessed up to From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Percentages are rounded off to the nearest decimal point.
Cohort A and B: Objective Response Rate (ORR) From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B ORR was defined as percentage of participants with partial response (PR) or complete response (CR) on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
Cohort A and B: Duration of Response (DOR) From randomization up to 27 months for Cohort A and up to 24.4 months for Cohort B DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first assessed up to 27 months for Cohort A and up to 24.4 months for Cohort B, for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Cohort C: ORR From enrollment up to 31 months ORR was defined as percentage of participants with PR or CR on 2 consecutive occasions ≥4 weeks apart as determined by the investigator using RECIST v.1.1, assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Percentages are rounded off to the nearest decimal point.
Cohort C: DOR From enrollment up to 31 months DOR was defined as the time from the first occurrence of a documented OR (CR or PR) to PD, as determined locally by the investigator through the use of RECIST v1.1, or death from any cause, whichever occurred first, assessed up to 31 months for this outcome measure. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.
Overall Survival (OS) From randomization/ enrollment (Cohort C) up to death from any cause, up to 45 months for Cohort A, up to 46 months for Cohort B and up to 31 months for Cohort C OS was defined as the time from randomization to death from any cause.
Cohort A and B: Change From Baseline in Global Health Status (GHS)/Health-Related Quality of Life (HRQoL) Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30 Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and 24 (cycle length=28 days) European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
Cohorts A and B:Plasma Concentration of Ipatasertib Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days) Cohort C: 1-year Event-free PFS Rate From enrollment until the occurrence of disease progression or death from any cause, whichever occurred earlier, up to 1 year PFS was defined as the time from enrollment to the first occurrence of disease progression, as determined locally by the investigator through the use of RECIST v.1.1, or death from any cause, whichever occurred first. Event-free PFS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Percentages are rounded off to the nearest decimal point. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Cohort C: Change From Baseline in GHS/HRQoL Score Measured by GHS/HRQoL Scale (Questions 29 and 30) of the EORTC QLQ-C30 Baseline, Day 1 of Cycles 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, and 44 (cycle length=28 days) EORTC QLQ-C30 is a cancer-specific instrument with 30 questions covering symptoms, functioning, and health-related quality of life (HRQoL). The participant's assessment of overall HRQoL is assessed by using the last 2 questions (29 and 30) of the instrument, with each of these items based on a 7-point scale (1=very poor to 7=excellent), which are then combined into the GHS/QoL multi-item scale. The scores obtained for each question were averaged into a raw score for the scale, and this raw score for the scale was then subsequently linearly transformed to a scale score of 0 to 100, with a high score indicating better GHS/QoL. Negative change from Baseline values in the GHS/QoL change from baseline analysis indicated deterioration in HRQoL and positive values indicated improvement.
Number of Participants With Adverse Events (AEs) Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE 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 were reported based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0.
Cohorts A and B: Plasma Concentration of G-037720 Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days ) G-037720 was a metabolite of ipatasertib.
Cohort C: 1-year Event-free OS Rate From enrollment up to death from any cause, up to 1 year OS was defined as the time from enrollment to death from any cause. Event-free OS rate was defined as percentage of participants who did not experience any event and survived at 1 year after enrollment. As prespecified in the protocol, this outcome measure was applicable only to Cohort C. Percentages were rounded off to the nearest decimal.
Cohort B: Time to Deterioration (TTD) in Pain Baseline up to 24.4 months Time to deterioration in GHS/HRQoL was defined as the time from randomization to first observed ≥ 11-point increase from Baseline in pain scale score (Question 9 and 19) in EORTC QLQ-C30 linearly transformed GHS/HRQoL scale score, assessed up 24.4 months for this outcome measure. TTD was planned to be assessed only in cohort with HR+/HER2 - breast cancer participants (Cohort B). Questions 9 and 19 that assessed pain, used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). The scores were linearly transformed on a scale of 0 to 100, with higher scores indicating increased severity in symptoms.
Cohort C: Plasma Concentration of Ipatasertib Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days) Cohort C: Serum Concentration of Atezolizumab Day 1 of Cycle 1: 30 minutes post dose, predose on Day 15 of Cycle 1 and predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (cycle length=28 days) As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Cohort C: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab Up to 45.5 months The numbers of ADA-positive participants after drug administration were summarized for participants exposed to atezolizumab. As prespecified in the protocol, this outcome measure was applicable only to Cohort C.
Number of Participants With at Least One Adverse Events of Special Interest (AESI) Up to 58.9 months for Cohort A, up to 59.9 months for Cohort B and up to 45.5 months for Cohort C An AE is any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. An AE 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 were reported based on the NCI CTCAE, Version 4.0. AESI include cases of potential drug-induced liver injury that include an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) in combination with either an elevated bilirubin or clinical jaundice, as defined by Hy's Law. Suspected transmission of an infectious agent by the study drug, Grade \>= 3 fasting hyperglycemia, hepatotoxicity, diarrhea, rash, ALT/AST elevations. Grade \>= 2 colitis/enterocolitis.
Cohort C: Plasma Concentration of G-037720 Days 1 and 15 of Cycle 1: 1 to 3 hours post dose, and on Day 15 of Cycle 3: 2 to 4 hours post dose (cycle length= 28 days ) G-037720 was a metabolite of ipatasertib.
Trial Locations
- Locations (176)
Oncologianova GmbH - Gesellschaft für Innovationen in der Onkologie
🇩🇪Recklinghausen, Germany
Kaiser Permanente - Roseville
🇺🇸Roseville, California, United States
Kaiser Permanente - South San Francisco
🇺🇸South San Francisco, California, United States
Memorial Sloan Kettering
🇺🇸New York, New York, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Kaiser Permanente - Oakland
🇺🇸Oakland, California, United States
Fundación CENIT para la Investigación en Neurociencias
🇦🇷Buenos Aires, Argentina
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
CHU Besançon - Hôpital Jean Minjoz
🇫🇷Besançon Cedex, France
Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
🇩🇪Freiburg, Germany
Polyclinique Bordeaux Nord Aquitaine
🇫🇷Bordeaux, France
UCSD Moores Cancer Center
🇺🇸La Jolla, California, United States
West Clinic
🇺🇸Germantown, Tennessee, United States
Agioi Anargyroi; 3Rd Dept. of Medical Oncology
🇬🇷Athens, Greece
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Dres. Andreas Köhler und Roswitha Fuchs
🇩🇪Langen, Germany
Universitätsfrauen- und Poliklinik am Klinikum Suedstadt
🇩🇪Rostock, Germany
Santa Casa de Misericordia de Salvador
🇧🇷Salvador, BA, Brazil
Masaryk?v onkologický ústav; Klinika komplexní onkologické pé?e
🇨🇿Brno, Czechia
Universitätsklinikum Würzburg; Frauenklinik
🇩🇪Würzburg, Germany
Praxis Dr.med. Katja Ziegler-Löhr
🇩🇪Köln, Germany
Hosp Provincial D. Centenarios; Oncology Dept
🇦🇷Rosario, Argentina
Cliniques Universitaires St-Luc
🇧🇪Bruxelles, Belgium
Indraprastha Apollo Hospitals
🇮🇳New Delhi, Delhi, India
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Sociedad de Investigaciones Medicas Ltda (SIM)
🇨🇱Temuco, Chile
ICIMED Instituto de Investigación en Ciencias Médicas
🇨🇷San José, Costa Rica
Cabrini Medical Centre; Oncology
🇦🇺Malvern, Victoria, Australia
GHdC Site Notre Dame
🇧🇪Charleroi, Belgium
Hospital Nossa Senhora da Conceicao
🇧🇷Porto Alegre, RS, Brazil
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Anticancer Hospital Ag Savas; 1St Dept of Internal Medicine
🇬🇷Athens, Greece
Szegedi Tudomanyegyetem, AOK, Szent-Gyorgyi Albert Klinikai Kozpont, Onkoterapias Klinika
🇭🇺Szeged, Hungary
National Hospital Organization Osaka National Hospital
🇯🇵Osaka, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Tokyo, Japan
Centro Médico Zambrano Hellion
🇲🇽Monterrey, Nuevo LEON, Mexico
Centro Medico Monte Carmelo
🇵🇪Arequipa, Peru
Instyt. Centrum Zdrowia Matki Polki; Klinika Chirurgii Onk. Chorób Piersi z Podod. Onko Klinicznej
🇵🇱?ód?, Poland
Hospital Provincial de Castellon; Servicio de Oncologia
🇪🇸Castellon de La Plana, Castellon, Spain
Universitätsklinikum des Saarlandes; Klinik f. Frauenheilkunden und Geburtshilfe
🇩🇪Homburg/Saar, Germany
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
Tokai University Hospital
🇯🇵Kanagawa, Japan
Saitama Cancer Center, Breast Oncology
🇯🇵Saitama, Japan
Inha University Hospital
🇰🇷Incheon, Korea, Republic of
Orszagos Onkologial Intezet; Onkologiai Osztaly X
🇭🇺Budapest, Hungary
Hyogo Medical University Hospital
🇯🇵Hyogo, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Hospital Nacional Cayetano Heredia; Ocología; Servicio de Hematología Oncología Médica
🇵🇪Lima, Peru
Oncosalud Sac; Oncología
🇵🇪Lima, Peru
Narodowy Instytut Onkologii im. M.Sklodowskiej-Curie; Klinika Nowotworow Piersi i Chirurgii Rekonstr
🇵🇱Warszawa, Poland
SBIH Kaluga Region Clinical Oncology Dispensary
🇷🇺Kaluga, Russian Federation
National Cancer Centre; Medical Oncology
🇸🇬Singapore, Singapore
Hospital Clinic Barcelona; Servicio de oncologia
🇪🇸Barcelona, Spain
Clínica San Gabriel; Unidad de Investigación Oncológica de la Clínica San Gabriel
🇵🇪Lima, Peru
Clinica Ricardo Palma
🇵🇪San Isidro, Peru
Federal State Institution, Moscow Research Oncology Institute n.a. P.A. Hertzen; Oncourology
🇷🇺Moscow, Moskovskaja Oblast, Russian Federation
National Cancer Institute MOH of Ukraine
🇺🇦Kiev, Ukraine
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Hospital Universitario Virgen del Rocio; Servicio de Oncologia
🇪🇸Sevilla, Spain
Katip Celebi University Ataturk Training and Research Hospital; Oncology
🇹🇷Izmir, Turkey
Royal Stoke University Hospital
🇬🇧Stoke-on-Trent, United Kingdom
Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
🇪🇸Santiago de Compostela, LA Coruña, Spain
Moscow City Oncology Hospital #62
🇷🇺Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation
FSI Rostov research oncological institute of MoH and SD of RF; PAD
🇷🇺Rostov-on-Don, Rostov, Russian Federation
Hospital Universitario Reina Sofia; Servicio de Oncologia
🇪🇸Córdoba, Cordoba, Spain
Dicle Uni Medical Faculty; Internal Medicine
🇹🇷Diyarbakir, Turkey
University Hospital coventry; Oncology Department
🇬🇧Coventry, United Kingdom
Hospital Universitario Puerta de Hierro; Servicio de Oncologia
🇪🇸Majadahonda, Madrid, Spain
Hospital del Mar; Servicio de Oncologia
🇪🇸Barcelona, Spain
HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio de Oncologia
🇪🇸Madrid, Spain
Medical Oncology Centre of Rosebank; Oncology
🇿🇦Johannesburg, South Africa
Chemotherapy SI Dnipropetrovsk MA of MOHU
🇺🇦Dnipropetrovsk, Ukraine
Medipol University Medical Faculty; Oncology Department
🇹🇷Istanbul, Turkey
National Taiwan Uni Hospital; General Surgery
🇨🇳Taipei, Taiwan
Sakarya University Medical School; Medical Oncology
🇹🇷Sakarya, Turkey
The Beatson West of Scotland Cancer Centre; Cancer Clinical Trials Unit
🇬🇧Glasgow, United Kingdom
Royal Marsden Hospital; Dept of Medical Oncology
🇬🇧Sutton, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
K. Permanente - Santa Clara
🇺🇸Santa Clara, California, United States
K. Permanente - Walnut Creek
🇺🇸Walnut Creek, California, United States
Calvary Mater Newcastle; Medical Oncology
🇦🇺Waratah, New South Wales, Australia
British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
Clinica CIMCA
🇨🇷San José, Costa Rica
Fakultni nemocnice Olomouc; Onkologicka klinika
🇨🇿Olomouc, Czechia
APHP - Hospital Saint Louis
🇫🇷Paris, France
Institut Jean Godinot; Oncologie Medicale
🇫🇷Reims CEDEX, France
Onkologische Schwerpunktpraxis Kurfürstendamm
🇩🇪Berlin, Germany
Euromedical General Clinic of Thessaloniki; Oncology Department
🇬🇷Thessaloniki, Greece
Mühlenkreiskliniken; Johannes Wesling Klinikum Minden; Klinik für Frauenheilkunde und Geburtshilfe
🇩🇪Minden, Germany
Borsod-Abauj-Zemplen Megyei Korhaz Es Egyetemi Oktato Korhaz; Onkologiai Osztaly
🇭🇺Miskolc, Hungary
Azienda Ospedaliero-Universitaria S.Orsola-Malpighi; Unità Operativa Oncologia Medica
🇮🇹Bologna, Emilia-Romagna, Italy
Ospedale Santa Maria Annunziata; Oncologia
🇮🇹Bagno a Ripoli, Toscana, Italy
National Hospital Organization Kyushu Cancer Center;Breast Oncology
🇯🇵Fukuoka, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Merida | Investigacion Clinica
🇲🇽Mérida, Yucatan, Mexico
PHI University Clinic of Radiotherapy and Oncology; Malignant diseases of thorax
🇲🇰Skopje, North Macedonia
Instituto Regional de Enfermedades Neoplasicas - IREN Norte
🇵🇪Trujillo, Peru
Blokhin Cancer Research Center; Combined Treatment
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
Clinical Oncology Dispensary of Ministry of Health of Tatarstan
🇷🇺Kazan, Tatarstan, Russian Federation
Institute of Oncology Ljubljana
🇸🇮Ljubljana, Slovenia
Hospital de Donostia; Servicio de Oncologia
🇪🇸Guipuzcoa, Spain
VETERANS GENERAL HOSPITAL; Department of General Surgery
🇨🇳Taipei, Taiwan
Prof. Dr. Cemil Tascioglu City Hospital; Med Onc
🇹🇷Istanbul, Turkey
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
Lviv State Oncological Regional Treatment and Diagnostic Center
🇺🇦Lviv, Ukraine
Rajiv Gandhi Cancer Inst.&Research Center; Medical Oncology
🇮🇳New Delhi, Delhi, India
Fiona Stanley Hospital; FSH Cancer Centre Clinical Trials Unit
🇦🇺Bull Creek, Western Australia, Australia
Centre Georges Francois Leclerc; Oncologie 3
🇫🇷Dijon, France
ICM; Medecine B3
🇫🇷Montpellier cedex 5, France
Centre Catherine De Sienne
🇫🇷Nantes, France
Ankara Bilkent City Hospital
🇹🇷Ankara, Turkey
Irccs Centro Di Riferimento Oncologico (CRO); Dipartimento Di Oncologia Medica
🇮🇹Aviano, Friuli-Venezia Giulia, Italy
Royal Marsden Hospital - London
🇬🇧London, United Kingdom
Hospital Araujo Jorge; Departamento de Ginecologia E Mama
🇧🇷Goiania, GO, Brazil
Instituto Nacional de Cancer - INCa; Oncologia
🇧🇷Rio de Janeiro, RJ, Brazil
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre, RS, Brazil
Faculdade de Medicina do ABC - FMABC
🇧🇷Santo Andre, SP, Brazil
Hospital Perola Byington
🇧🇷Sao Paulo, SP, Brazil
Vall d?Hebron Institute of Oncology (VHIO), Barcelona
🇪🇸Barcelona, Spain
Hospital Ramon y Cajal; Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Clinico Universitario; Oncologia
🇪🇸Valencia, Spain
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Zala County Hospital ICU
🇭🇺Zalaegerszeg, Hungary
Kanagawa Cancer Center
🇯🇵Kanagawa, Japan
Kinki University Hospital, Faculty of Medicine; Surgery
🇯🇵Osaka, Japan
Shizuoka Cancer Center
🇯🇵Shizuoka, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Showa University Hospital; Breast Surgery
🇯🇵Tokyo, Japan
Memorial Sloan Kettering Cancer Center at Westchester
🇺🇸Harrison, New York, United States
Hospital do Câncer de Londrina
🇧🇷Londrina, PR, Brazil
Universitätsklinikum Hamburg-Eppendorf; Frauenklinik
🇩🇪Hamburg, Germany
Hetenyi Geza County Hospital; Onkologiai Kozpont
🇭🇺Szolnok, Hungary
CENEIT Oncologicos; DENTRO DE CONDOMINIO SAN FRANCISCO
🇲🇽Mexico City, Mexico
PHI University Clinic of Radiotherapy and Oncology; Breast malignancy
🇲🇰Skopje, North Macedonia
Instituto Nacional de Enfermedades Neoplasicas
🇵🇪Lima, Peru
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
St. Marianna University Hospital
🇯🇵Kanagawa, Japan
Kumamoto Shinto General Hospital
🇯🇵Kumamoto, Japan
Centro Medico Dalinde
🇲🇽Cdmx, Mexico CITY (federal District), Mexico
Hospital Daniel Alcides Carrion
🇵🇪Callao, Peru
Narodowy Inst.Onkol.im.Sklodowskiej-Curie Panstw.Inst.Bad Gliwice; III Klin. Radioter. i Chemioter.
🇵🇱Gliwice, Poland
Ivanovo Regional Oncology Dispensary
🇷🇺Ivanovo, Russian Federation
Clinical Hospital; Oncology Department
🇲🇰Bitola, North Macedonia
St. Luke's International Hospital
🇯🇵Tokyo, Japan
National University Hospital; National University Cancer Institute, Singapore (NCIS)
🇸🇬Singapore, Singapore
Arkhangelsk Regional Clinical Oncology Dispensary
🇷🇺Arkhangelsk, Arhangelsk, Russian Federation
S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
🇷🇺Saint-Petersburg, Sankt Petersburg, Russian Federation
Chi Mei Medical Center Liou Ying Campus
🇨🇳Liuying Township, Taiwan
Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
🇨🇳Taipei City, Taiwan
Kyiv City Clinical Oncological Center, Day Hospital Department for Oncological patients
🇺🇦Kiev, Ukraine
USC Norris Cancer Center
🇺🇸Los Angeles, California, United States
USC Norris Cancer Center; USC Oncology Hematology Newport Beach
🇺🇸Newport Beach, California, United States
Kaiser Permanente - San Francisco (2238 Geary)
🇺🇸San Francisco, California, United States
UCSF Comprehensive Cancer Ctr
🇺🇸San Francisco, California, United States
UC Davis; Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Kaiser Permanente Sacramento Medical Center
🇺🇸Sacramento, California, United States
Kaiser Permanente - San Leandro
🇺🇸San Leandro, California, United States
Texas Oncology, P.A.
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center; Simmons Comprehensive Cancer Center, Simmons Pharmacy
🇺🇸Dallas, Texas, United States
Kaiser Permanente - Vallejo
🇺🇸Vallejo, California, United States
Memorial Regional Hospital
🇺🇸Hollywood, Florida, United States
UF Health Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
Memorial Hospital West
🇺🇸Pembroke Pines, Florida, United States
University of Maryland
🇺🇸Baltimore, Maryland, United States
Mercy Medical Center
🇺🇸Baltimore, Maryland, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Oncology Consultants PA
🇺🇸Houston, Texas, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Istituto Nazionale Tumori Irccs Fondazione g. PASCALE;U.O.C. Oncologia Medica Senologica
🇮🇹Napoli, Campania, Italy
K. Permanente - San Jose
🇺🇸San Jose, California, United States
IOV - Istituto Oncologico Veneto - IRCCS; Oncologia Medica II
🇮🇹Padova, Veneto, Italy
Westmead Hospital; Medical Oncology
🇦🇺Wentworthville, New South Wales, Australia
Mater Hospital; Cancer Services
🇦🇺South Brisbane, Queensland, Australia