Axitinib For The Treatment Of Advanced Hepatocellular Carcinoma

Phase 2

Completed

Conditions: Hepatocellular Carcinoma

Interventions: Drug: Axitinib (AG-013736)
Drug: Placebo
Other: Best Supportive Care

Registration Number: NCT01210495

Lead Sponsor: Pfizer

Brief Summary: The study is designed to demonstrate that axitinib plus best supportive care is superior to placebo plus best supportive care in prolonging survival in patients with advanced hepatocellular carcinoma.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 224

Inclusion Criteria

Locally advanced or metastatic HCC
Failure of one prior antiangiogenic therapy including sorafenib, bevacizumab and brivanib.
Child-Pugh Class A or B (score 7 only) disease.

Exclusion Criteria

Prior treatment of advanced HCC with more than one prior first-line systemic therapy.
Any prior local therapy within 2 weeks of starting the study treatment.
Presence of hepatic encephalopathy and/or clinically relevant ascites.
Presence of main portal vein invasion by HCC.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Axitinib (AG-013736)	Participants in this group received axitinib + best supportive care. Participants with Child-Pugh Class A disease (score 5 or 6) were enrolled into the randomized portion at a starting axitinib dose of 5 mg BID orally. Participants with Child-Pugh Class B disease (score 7) were to begin enrollment into the randomized portion of the study following determination of the recommended axitinib starting dose in the non-randomized portion. Study treatment was administered in cycles of 4 weeks in duration
A	Best Supportive Care	Participants in this group received axitinib + best supportive care. Participants with Child-Pugh Class A disease (score 5 or 6) were enrolled into the randomized portion at a starting axitinib dose of 5 mg BID orally. Participants with Child-Pugh Class B disease (score 7) were to begin enrollment into the randomized portion of the study following determination of the recommended axitinib starting dose in the non-randomized portion. Study treatment was administered in cycles of 4 weeks in duration
B	Placebo	Participants in this group received placebo + best supportive care. Treatment was administered in cycles of 4 weeks in duration. The starting dose of placebo for participants with Child Pugh Class A disease (score 5 or 6) was chosen as 5 mg BID. Participants with Child-Pugh Class B, score 7 received placebo that was determined from the non-randomized portion of the study until the recommended starting dose was determined, participants with Child-Pugh Class B, score 7, were not permitted to enter the randomized portion of the study
B	Best Supportive Care	Participants in this group received placebo + best supportive care. Treatment was administered in cycles of 4 weeks in duration. The starting dose of placebo for participants with Child Pugh Class A disease (score 5 or 6) was chosen as 5 mg BID. Participants with Child-Pugh Class B, score 7 received placebo that was determined from the non-randomized portion of the study until the recommended starting dose was determined, participants with Child-Pugh Class B, score 7, were not permitted to enter the randomized portion of the study

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS) - Stratified Analysis, Randomized Portion	From randomization until at least two years after the last participant has been randomized (up to 6 years)	OS was defined as the time from the date of randomization to the date of death due to any cause. OS (in months) was calculated as (date of death - first randomization date +1)/30.4. For participants still alive at the time of the analysis, the OS time was censored on the last date they were known to be alive. All participants were followed up for survival at least every 3 months after discontinuing study treatment until at least two years after randomization of the last participant.

Secondary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) - Stratified Analysis, Randomized Portion	Every 8 weeks until disease progression/death or start of new treatment or until at least two years after the last participant has been randomized, whatever occurs first	PFS was defined as time from randomization to first documented objective tumor progression or to death due to any cause, whichever occurred first. PFS (in months) was calculated as (first event date - first randomization date +1)/30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease \[PD\]), or from adverse event (AE) data (where the outcome was death). As per response evaluation criteria in solid tumors (RECIST) 1.1, progression was defined as greater than or equal to (\>=) 20% increase in sum of longest dimensions of target lesions or appearance of one or more new target lesions and unequivocal progression of existing non-target lesions, or appearance of 1 new non-target lesions. Participants discontinuing study treatment without documented evidence of PD were to be followed up at least every 8 weeks after discontinuing study treatment until disease progression, or initiation of another anticancer treatment.
Objective Response Rate (ORR) - Percentage of Participants With Objective Response by Stratified Analysis, Randomized Portion	Every 8 weeks until at least two years after the last participant has been randomized	ORR was defined as the percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to the RECIST 1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must decrease to normal (short axis \<10 millimetres \[mm\]). PR was defined as a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time to Tumor Progression (TTP) - Stratified Analysis, Randomized Portion	Every 8 weeks until disease progression/death or start of new treatment or until at least two years after the last participant has been randomized, whatever occurs first	TTP was defined as the time from randomization to first documentation of objective tumor progression. If tumor progression data included more than 1 date, the first date was used. TTP (in months) was calculated as (first event date - first randomization date +1)/30.4.
Duration of Response (DR) by Unstratified Analysis, Randomized Portion	From objective response to date of progression or death	DR was defined as the time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed to the first documentation of PD or to death due to any cause, whichever occurs first. If tumor progression data included more than 1 date, the first date was to be used. DR (in months) was to be calculated as (the end date for DR - first CR or PR that was subsequently confirmed +1)/30.4.
Percentage of Participants With Overall Clinical Benefit Response (CBR) - Stratified Analysis, Randomized Portion	From Baseline up to end of treatment	CBR was defined as the percentage of participants with confirmed CR or confirmed PR or a best response of stable disease \>=8 weeks according to RECIST 1.1 criteria, relative to all randomized participants who had baseline measurable disease. Confirmed responses were defined as those that persisted on repeat imaging study \>=4 weeks after the initial documentation of response. Participants who did not have on study radiographic tumor re-evaluation or who died, progressed, or dropped out for any reason prior to reaching a CR, PR, or stable disease were counted as non-responders in the assessment of CBR. A participant who initially met the criteria for a PR and then subsequently became a confirmed CR was to be assigned a best response of CR.
Axitinib Steady-State Pharmacokinetic (PK) Parameter - Maximum Observed Plasma Concentration (Cmax), Non-Randomized Portion	Cycle 1 Day 15	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing.
Axitinib Steady-State PK Parameter - Area Under the Plasma Concentration Versus Time Curve From 0 to 24 Hour (AUC0-24), Non-Randomized Portion	Cycle 1 Day 15	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing. In the below table, 4 participants in Child-Pugh A and 1 participant in Child-Pugh B were not reported due to nonestimable half-life.
Axitinib Steady-State Pharmacokinetic Parameter - Time to First Occurrence of Cmax (Tmax), Non-Randomized Portion	Cycle 1 Day 15	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing.
Axitinib Steady-State Pharmacokinetic Parameter - Apparent Oral Clearance (CL/F), Non-Randomized Portion	Cycle 1 Day 15	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing. In the below table, 4 participants in Child-Pugh A and 1 participant in Child-Pugh B were not reported due to nonestimable half-life.
Axitinib Steady-State Pharmacokinetic Parameter - Terminal Plasma Elimination Half-Life (t1/2), Non-Randomized Portion	Cycle 1 Day 15	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing. In the below table, 4 participants in Child-Pugh A and 1 participant in Child-Pugh B were not reported due to nonestimable half-life.
Axitinib Steady-State Pharmacokinetic Parameter - Apparent Oral Volume of Distribution of the Drug During the Elimination Phase (Vz/F), Non-Randomized Portion	Cycle 1 Day 15	Axitinib samples were to be collected from all participants on Cycle 1 Day 15 at the following time points: pre-dose, 1, 2, 3, 4, 6 and 8 hours after axitinib dosing. The PK parameter, Vz/F has been presented in this outcome measure. In the below table, 4 participants in Child-Pugh A and 1 participant in Child-Pugh B were not reported due to nonestimable half-life.
Concentration of Soluble Proteins at Baseline in Randomized Portion	Baseline	Plasma soluble proteins interleukin-6 (IL-6), E-Selectin, interleukin-8 (IL-8), hepatocyte growth factor (HGF), matrix metalloproteinase-2 (MMP-2), stem cell factor (SCF), angiopoietin-2 (Ang-2), vascular endothelial growth factor-A (VEGF-A), vascular endothelial growth factor-C (VEGF-C), soluble vascular endothelial growth factor receptor 2 (sVEGFR2), soluble vascular endothelial growth factor receptor 3 (sVEGFR3), stromal cell-derived factor-1 (SDF1), neutrophil gelatinase-associated lipocalin (NGAL), migration inhibitory factor (MIF), c-MET, regulated upon activation normal T cell expressed and presumably secreted (RANTES), and monocyte chemotactic protein-3 (MCP-3) were only measured in randomized participants.
Percentage of Participants With Specific Micro-Ribonucleic Acid (miRNA) Transcript Present in Circulation in Randomized Portion	Baseline	A 5 millilitres (mL) whole blood sample was collected from all randomized participants to evaluate the miRNA transcripts.
Functional Assessment of Cancer Therapy - Hepatobiliary Questionnaire (FACT-Hep) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date	FACT-Hep consists of 27-item FACT-G, and 18-item Hepatobiliary Subscale. FACT-Hep questionnaire uses 5-point Likert rating scale, range '0'-not at all to '4'. FACT-Hep total score ranges from 0 to 180, where highest score represents maximum achievable quality of life. Domains of FACT-G include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB) and Functional Well-Being (FWB). Hepatobiliary disease specific items include: swelling or cramps, losing weight, gastrointestinal (GI)-related questions, lack of energy, side effects, pain, fatigue, usual activities, jaundice, fevers, itching, taste of food and chills. Eight of the items (pain, back pain, stomach pain/discomfort, lack of energy, fatigue, nausea, weight loss and jaundice) make up FACT-Hepatobiliary Symptom Index (FHSI-8), and are considered to be symptoms specific to hepatobiliary cancer. Table below included mixed effect model estimated average based on all observed values/time points.
Functional Assessment of Cancer Therapy - General (FACT-G) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date	FACT-G is core questionnaire of Functional Assessment of Chronic Illness Therapy (FACIT) measurement system to evaluate QoL in cancer population. FACT-G consisted of 27 questions grouped in 4 domains of general Health-Related QoL (HRQoL): PWB, SWB, EWB and FWB; each ranging from 0 (not at all) to 4 (very much). FACT-G ranged between 0 and 108. Since questions could be reversed coded, as appropriate, before calculating FACT-G, 0 and 108 could be considered worst and best health states. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.
Functional Assessment of Cancer Therapy (FACT)-Hepatobiliary Symptom Index-8 (FHSI-8) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date	The FACT-Hep includes the FACT-G and a hepatobiliary module. The hepatobiliary disease specific items include: swelling or cramps, losing weight, GI related questions, lack of energy, side effects, pain, fatigue, usual activities, jaundice, fevers, itching, taste of food and chills. Eight of the items (pain, back pain, stomach pain/discomfort, lack of energy, fatigue, nausea, weight loss, and jaundice) make up the FHSI-8, and are considered to be symptoms specific to hepatobiliary cancer. FHSI-8 total score ranges from 0 to 32 where "0" is a severely symptomatic participant and the highest score indicates an asymptomatic participant. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.
Functional Assessment of Cancer Therapy-G (FACT-G) Subscales in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date	FACT-G is core questionnaire of Functional Assessment of Chronic Illness Therapy (FACIT) measurement system to evaluate QoL in cancer population. FACT-G consisted of 27 questions grouped in 4 domains of general HRQoL: PWB, SWB, EWB and FWB. Each of the individual subscale, except EWB has 7 items and each integer scored 0 to 4 making a maximum possible score of 28 (range 0 to 28). EWB has 6 items and each integer scored 0 to 4 making a maximum possible score of 24 (range 0 to 24). For all the 4 scales, higher values correspond to better health. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.
Functional Assessment of Cancer Therapy - Hepatobiliary Cancer Subscale (FACT Hep-CS18) Questionnaire in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date	This subscale consists of 18 items rated on a scale from '0' - not at all to '4' - very much regarding how much each item was present in the last 7 days. FACT-Hep-CS18 total score ranges from 0 to 72. The higher score reflects better QoL or fewer symptoms. The 18 items of this scale are associated with hepatocellular carcinoma. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.
Functional Assessment of Cancer Therapy - Hepatobiliary Cancer Trial Outcome Index (FACT Hep-TOI) Questionnaire in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date	The trial outcome index is defined to be the sum (PWB+FWB+HepCS), making it 32 items altogether. Each ranges from '0' - not at all to '4' - very much regarding how much each item was present in the last 7 days. FACT Hep -TOI total score ranges from 0 to 128, where the highest score represents a maximum achievable quality of life. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.
Time to Deterioration (TTD) Based on the Composite Endpoint in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	From randomization to death or tumor progression or FHSI-8 mean score decrease >=3 points, whichever comes first	TTD analysis was performed for FHSI-8. Time to deterioration was defined as the time between date of randomization and date of the event.
EuroQoL (EQ-5D)- Health State Profile Utility Score in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.
EuroQoL Visual Analogue Scale (EQ-VAS) in Randomized Portion: Overall Between-Treatment Comparison Based on the Repeated Measures Mixed Effects Model	Cycle 1 Day 1 pre-dose and before any other clinical assessments, every 4 weeks thereafter while on study, at end of study treatment/withdrawal, and follow-up and at Day 28 after last dose date	EQ-5D VAS in rates the participant's overall health status using values from 0 (worst imaginable) to 100 (best imaginable). The below table included the model estimated average based on all the observed values/time points. The mixed effect model was used.
Number of Participants With Dose-Limiting Toxicities (DLTs) in Non-Randomized Portion	Cycle 1 (4 weeks)	Number of Child-Pugh Class B (score 7) participants with DLT was evaluated during Cycle 1 of treatment in the non-randomized portion of the study.
Number of Participants With Treatment-Emergent Adverse Events (AEs) in Non-Randomized Portion	Up to 28 days after last dose of study drug (up to 6 years)	An AE was an untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. The grade of an AE was determined according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
Number of Participants With Treatment-Related Adverse Events (AEs) in Non-Randomized Portion	Up to 28 days after last dose of study drug (up to 6 years)	Treatment-related AE was any untoward medical occurrence in a participant with causal relationship to the study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The grade of an AE was determined according to CTCAE Version 3.0.
Number of Participants With Treatment-Emergent Adverse Events (AEs) in Randomized Portion	Up to 28 days after last dose of study drug (up to 6 years)	An AE was an untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes: death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. The grade of an AE was determined according to CTCAE Version 3.0.
Number of Participants With Treatment-Related Adverse Events (AEs) in Randomized Portion	Up to 28 days after last dose of study drug (up to 6 years)	Treatment-related AE was any untoward medical occurrence in a participant with causal relationship to the study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The grade of an AE was determined according to CTCAE Version 3.0.

Trial Locations

Locations (76): Moores UCSD Cancer Center
🇺🇸
La Jolla, California, United States
UCSD Medical Center- La Jolla
🇺🇸
La Jolla, California, United States
Comprehensive Cancer Centers of Nevada
🇺🇸
Las Vegas, Nevada, United States
Alta Bates Summit Comprehensive Cancer Center
🇺🇸
Berkeley, California, United States
Hopital De La Croix-Rousse
🇫🇷
Lyon Cedex 04, France
Bichat-Beaujon Service Inter Hospitalier De Cancerologie
🇫🇷
Clichy, France
UCSD Medical Center- Hillcrest
🇺🇸
San Diego, California, United States
Medizinische Klinik mit Schwerpunkt
🇩🇪
Berlin, Germany
The Christie NHS Foundation Trust
🇬🇧
Withington, Manchester, United Kingdom
The First Affiliated Hospital of Anhui Medical University
🇨🇳
Hefei, Anhui, China
Guangdong General Hospital
🇨🇳
Guangzhou, Guangdong, China
The PLA 307 Hospital
🇨🇳
Beijing, China
Zhongshan Hospital Fudan University
🇨🇳
Shanghai, China
Sir Run Run Shaw Hospital of College of Medicine of Zhejiang University
🇨🇳
Hangzhou, Zhejiang, China
Hôpital Saint Antoine
🇫🇷
Paris, France
Royal Liverpool and Broadgreen University Hospital
🇬🇧
Liverpool, United Kingdom
Chang Gung Medical Foundation Linkou Branch
🇨🇳
Taoyuan, Taiwan
Taichung Veterans General Hospital
🇨🇳
Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳
Tainan, Taiwan
Changhua Christian Hospital
🇨🇳
Changhua, Taiwan
Sasaki Foundation Kyoundo Hospital
🇯🇵
Chiyoda-Ku, Tokyo, Japan
Chi-Mei Medical Center LiouYing
🇨🇳
Tainan, Taiwan
Nanjing Bayi Hospital
🇨🇳
Nan Jing, Jiangsu, China
University of California Irvine Medical Center
🇺🇸
Orange, California, United States
Florida Hospital Transplant Center, Liver Unit
🇺🇸
Orlando, Florida, United States
Jiang Su Cancer Hospital
🇨🇳
Nanjing, Jiangsu, China
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Hospital of the University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Penn Presbyterian Medical Center
🇺🇸
Philadelphia, Pennsylvania, United States
Moffitt Cancer Center & Research Institute
🇺🇸
Tampa, Florida, United States
Universitair Ziekenhuis Gent
🇧🇪
Gent, Belgium
CHC Clinique Saint-Joseph
🇧🇪
Liège, Belgium
Nebraska Methodist Hospital
🇺🇸
Omaha, Nebraska, United States
CHU Cote de Nacre
🇫🇷
Caen, cedex 05, France
Hopital Saint André
🇫🇷
Bordeaux Cedex, France
Centre Hospitalier Universitaire d'Amiens
🇫🇷
Amiens, France
UPCET-CIC Timone
🇫🇷
Marseille, France
CHRU Montpellier-Hopital Saint Eloi - Departement Oncologie Medicale
🇫🇷
Montpellier Cedex 05, France
Hôpital L'Archet Ii
🇫🇷
Nice, France
Centre Eugène Marquis
🇫🇷
Rennes, France
CHRU de Purpan.
🇫🇷
Toulouse Cedex, France
Universitätsklinikum Bonn
🇩🇪
Bonn, Germany
Klinikum der Ludwig-Maximilians-Universitaet , Campus Grosshadern
🇩🇪
München, Germany
Policlinico S.Orsola-Malpighi Dipartimento di Ematologia e Scienze Oncologiche "L. E A. Seragnoli"
🇮🇹
Bologna, Italy
Semmelweis Egyetem I.sz. Belgyógyászati Klinika
🇭🇺
Budapest, Hungary
Istituto di Ematologia ed Oncologia Medica, Lorenzo ed Ariosto Seragnoli,
🇮🇹
Bologna, Italy
Szegedi Tudományegyetem Onkoterápiás Klinika
🇭🇺
Szeged, Hungary
Ospedale Versilia,Oncologia Medica
🇮🇹
Lido Di Camaiore (LU), Italy
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori IRST
🇮🇹
Meldola (FC), Italy
Unita Operativa Oncologia Medica IRCCS Fondazione Salvatore Maugeri
🇮🇹
Pavia, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹
Roma, Italy
Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria aile Scotte
🇮🇹
Siena, Italy
Shizuoka Cancer Center
🇯🇵
Suntou-gun, Shizuoka, Japan
Unità Operativa Oncologica Medica
🇮🇹
Roma, Italy
Kinki University Hospital
🇯🇵
Osaka-Sayama, Osaka, Japan
Aichi Cancer Center Central Hospital, Diagnostic and Interventional Radiology
🇯🇵
Nagoya, Aichi, Japan
Gifu Municipal Hospital
🇯🇵
Gifu-shi, Gifu, Japan
Chiba University Hospital
🇯🇵
Chiba City, Chiba, Japan
Kanazawa University Hospital
🇯🇵
Kanazawa, Ishikawa, Japan
Yamanashi Prefectural Central Hospital
🇯🇵
Kofu-Shi, Japan
Nihon University Itabashi Hospital
🇯🇵
Itabashi-Ku, Tokyo, Japan
National Cancer Center/ Center for Liver Cancer
🇰🇷
Goyang-si, Korea, Republic of
Samsung Medical Center, Division of Hematology-Oncology, Department of Medicine
🇰🇷
Seoul, Korea, Republic of
Nemocnica Poprad, a.s.
🇸🇰
Poprad, Slovakia
Asan Medical Center, Division of Oncology, Department of Internal Medicine
🇰🇷
Seoul, Korea, Republic of
Narodny onkologicky ustav
🇸🇰
Bratislava, Slovakia
Fakultna nemocnica s poliklinikou F. D. Roosevelta Banska Bystrica
🇸🇰
Banska Bystrica, Slovakia
POKO Poprad s.r.o.
🇸🇰
Poprad, Slovakia
Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital
🇨🇳
Kaohsiung, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
Clatterbridge Centre for Oncology NHS Foundation Trust
🇬🇧
Liverpool, United Kingdom
Royal Free Hospital
🇬🇧
London, United Kingdom
King's College Hospital NHS Foundation Trust
🇬🇧
London, United Kingdom
Hammersmith Hospital
🇬🇧
London, United Kingdom
Queen Mary Hospital
🇭🇰
Hong Kong, Hong Kong
Prince of Wales Hospital
🇭🇰
Shatin, N.T., Hong Kong