The BURAN Study of Buparlisib in Patients With Recurrent or Metastatic HNSCC

Phase 3

Active, not recruiting

• Conditions: Head and Neck Cancer
• Interventions: Drug: Buparlisib & Paclitaxel

• Registration Number: NCT04338399
• Lead Sponsor: Adlai Nortye Biopharma Co., Ltd.

Brief Summary

The BURAN study is a randomized, open-label phase III study to assess the treatment effect of once-daily buparlisib in combination with weekly paclitaxel compared to weekly paclitaxel alone in patients with refractory, recurrent, or metastatic head and neck squamous cell carcinoma (HNSCC) that have progressed after prior anti PD 1/anti PD L1 monotherapy; prior anti PD 1/anti PD L1 therapy in combination with platinum-based therapy; or after sequential treatment of anti PD 1/anti PD L1 therapy, either prior to or post, platinum-based therapy.

Detailed Description

This study is to assess the impact on overall survival of the combination of Buparlisib and paclitaxel compared to paclitaxel alone in patients with prior anti PD 1/anti PD L1 monotherapy; prior anti PD 1/anti PD L1 therapy in combination with platinum-based therapy; or after sequential treatment of anti PD 1/anti PD L1 therapy, either prior to or post, platinum-based therapy.

Study Timeline

• Study First Submitted: 2020-03-18
• Study First Submitted QC: 2020-04-06
• Study First Posted: 2020-04-08
• Study Start: 2020-12-12
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-12
• Last Update Posted: 2025-02-14
• Primary Completion: 2025-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 483

Inclusion Criteria

1. Aged ≥18 years old.

2. Able to provide informed consent obtained before any trial related activities and according to local guidelines.

3. Patient has histologically and/or cytologically-confirmed HNSCC.

4. Patient has archival or new tumor tissue for the analysis of biomarkers and confirmation of HPV status (if unknown). One tumor block (preferred) or a recommended minimum of 5 unstained slides for patients with known HPV status (for tumor DNA characterization) or a recommended minimum of 10 slides for patients whose HPV status is unknown (5 slides for HPV testing plus 5 slides needed for biomarker testing). Enrollment in the study is contingent on confirmation of the availability of an adequate amount of tumor tissue, except in rare special circumstances, which must be reviewed and approved by the sponsor.

5. Patient has either progressive or recurrent disease after treatment with PDL1/PD1 based therapy for recurrent or metastatic disease:

   1. PDLl/PD1 therapy alone for metastatic (monotherapy) disease
   2. PDL1/PD1 in combination with chemotherapy for metastatic and recurrent disease
   3. PDL1/PD1 used for metastatic disease, after or prior to receiving a platinum agent for locally advanced or metastatic disease.
6. 6. Patient has received no more than two prior lines of systemic treatment for HNSCC (single agent chemotherapy used as a radiosensitizer is not counted as a prior line of therapy).

7. Patient has measurable disease as determined per RECIST version 1.1. If the only site of measurable disease is a previously irradiated lesion, documented progression of disease and a four-week period since radiotherapy completion is required.

8. Patient has adequate bone marrow function and organ function as shown by the following:

   1. Absolute neutrophil count (ANC) ≥1.5 x 109/L.

   2. Hemoglobin ≥9 g/dL (which may be reached by transfusion).

   3. Platelets ≥100 x 109/L (which may be reached by transfusion).

   4. International normalized ratio (INR) ≤1.5.

   5. Calcium (corrected for serum albumin) within normal limits (WNL) or ≤ grade 1 severity according to NCI-CTCAE version 5.0 if judged clinically not significant by the Investigator.

      Patients concomitantly taking bisphosphonates or denosumab for calcium correction are eligible.

   6. Normal potassium and magnesium levels.

   7. Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ 1.5 x upper limit of normal (ULN) or < 3.0 x ULN if liver metastases are present.

   8. Total serum bilirubin ≤ ULN or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin below or within normal range in patients with well documented Gilbert's Syndrome. Gilbert's syndrome is defined as presence of episodes of unconjugated hyperbilirubinemia with normal results from cells blood count (including normal reticulocyte count and blood smear), normal liver function test results, and absence of other contributing disease processes at the time of diagnosis.

   9. Serum creatinine ≤ 1.5 x ULN or calculated and directly measured creatinine clearance (CrCL) > 30 mL/min.

   10. Haemoglobin A1c (glycosylated hemoglobin; HbA1c) ≤8%.

9. Patient has Eastern Cooperative Oncology Group (ECOG) performance status ≤1.

10. Patient is able to swallow and retain oral medication. Patients able to swallow oral medication but mostly self-nourished through gastric or jejunal feeding tube are eligible.

11. Patients must apply highly effective contraception during and throughout the study, as well after the final dose of study treatment

Exclusion Criteria

Patients meeting any of the following criteria will not be eligible for participation in the study:

1. Patient has received previous treatment with any protein kinase B (PKB/AKT), mammalian target of rapamycin (mTOR) inhibitors, or phosphatidylinositol 3 kinase (PI3K) pathway inhibitors.

2. Patient received treatment with a taxane as part of prior treatment for metastatic disease.

3. Patient has symptomatic central nervous system (CNS) metastases. Patients with asymptomatic CNS metastases may participate in this study. Patient must have completed any prior local treatment for CNS metastases ≥ 28 days prior to the start of study treatment (including radiotherapy) and must be on a stable low dose of corticosteroid therapy. Radiosurgery must have been completed at least 14 days prior to start of study treatment.

4. Patient has received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study treatment or who have adverse events which have not recovered to grade 1 or better from previous chemotherapy treatment (except alopecia, autoimmune endocrine events must be stable and controlled).

5. Patient has grade ≥ 2 neuropathy, colitis, pneumonitis, , and uncontrolled endocrinopathies (e.g., hypothyroidism, diabetes with hemoglobin A1c > 8%) from previous treatment

6. Patient has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects.

7. Patient is currently receiving increasing or chronic treatment (>5 days) with corticosteroids or another immunosuppressive agent. The following uses of corticosteroids are permitted: single doses; standard premedication for paclitaxel, topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops, or local injections (e.g., intra-articular), or < 10 mg prednisolone or equivalent.

8. Patient is being treated at start of study treatment with any of the following drugs:

   1. Drugs known to be strong or moderate inhibitors or inducers of isoenzyme cytochrome P450 3A4 (CYP3A4) including herbal medications (see Table 16).
   2. Drugs with a known risk of inducing Torsades de Pointes. Note: The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated. Switching to a different medication prior to starting study treatment is allowed.

9. Patient is currently receiving warfarin or other coumarin-derived anti-coagulant, for treatment, prophylaxis, or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), fondaparinux or new oral anticoagulants (NOACs) is allowed.

10. Patient has a known hypersensitivity and/or contraindication to paclitaxel, standard premedication for paclitaxel, or other products containing Cremophor®.

11. Patient has other concurrent severe and/or uncontrolled medical conditions that would, in the Investigator's judgment, contraindicate patient participation in the clinical study (e.g., active or uncontrolled severe infection, chronic active hepatitis, immunocompromised, acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung disease, etc).

12. Patient has a known history of human immunodeficiency virus (HIV) infection (testing not mandatory).

13. Patient has any of the following cardiac abnormalities:

    1. Symptomatic congestive heart failure within 12 months of the screening period.
    2. History of documented congestive heart failure (New York Heart Association functional classification III-IV) or documented cardiomyopathy and left ventricular ejection fraction (LVEF) <50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO).
    3. Myocardial infarction ≤six months prior to enrollment.
    4. Unstable angina pectoris.
    5. Serious uncontrolled cardiac arrhythmia.
    6. Symptomatic pericarditis.
    7. QT interval corrected according to the formula of Fridericia (QTcF) > 450 msec for males and > 470 msec for females, on the screening electrocardiogram (ECG).
    8. Currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study treatment.

14. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study treatment (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).

15. Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g., risk of doing harm to self or others), or active severe personality disorders (defined according to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition [DSM-V]) are not eligible. Note: For patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous six weeks prior to start of study treatment.

16. Patient has other prior or concurrent malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, or other adequately treated in situ cancer, early gastric or GI cancer resected completely by endoscopy procedures or any other cancer from which the patient has been disease free for ≥ 3years.

17. Patient has a history of non-compliance to any medical regimen or inability to grant consent.

18. Patient is concurrently using or has used another approved or investigational cancer agent within 4 weeks of randomization.

19. Patient is pregnant or nursing (lactating). Patients with elevated human chorionic gonadotrophin (hCG) at baseline that is judged to be related to the tumor are eligible if hCG levels do not show the expected doubling when repeated five to seven days later, or pregnancy has been ruled out by vaginal ultrasound.

20. Patient has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated vaccines, and are not allowed. Non-live COVID vaccinations or boosters should not occur within 30 days of study start.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Weekly Paclitaxel	Buparlisib & Paclitaxel	Patients will receive weekly paclitaxel (80 mg/m2) administered intravenously (IV) on Days 1, 8, and 15 of a 21-day treatment cycle. Treatment will continue until disease progression, unacceptable toxicity, death or discontinuation for any other reason.
Buparlisib & Weekly Paclitaxel	Buparlisib & Paclitaxel	Drug: Patients will receive 100 mg (2 x 50 mg) buparlisib hard gel capsule administered orally, once daily starting on Day 1 of Treatment Cycle 1, Drug: Paclitaxel (80 mg/m2) administered intravenously (IV) on Days 1, 8, and 15 of a 21-day treatment cycle. Treatment will continue until disease progression, unacceptable toxicity, death or discontinuation for any other reason.

Primary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Overall survival will be measured from time of randomization until death from any cause. The analysis will occur when all patients have been randomized and followed for 12 months.	To assess the OS of buparlisib in combination with paclitaxel compared to paclitaxel alone in patients with recurrent or metastatic HNSCC

Secondary Outcome Measures

Name	Time	Method
Progression free survival	PFS will be assessed up to 24 months after all patients are randomized	Defined as the time from randomization date until tumor progression or death from any cause.
Overall Response Rate	ORR will be assessed for all patients 6 months after randomization is complete.	Defined at the proportion of patients with a complete or partial response
Health Related Quality of Life (QoL): Time to Definitive deterioration of Quality of Life as assessed by EORTC C30 questionnaire	Assessments will be made from randomization until treatment discontinuation	A summary of EORTC-QLQ-C30 scores by time window. Time to deterioration is the number of days between the date of randomization and the date of the assessment when definitive deterioration is seen. Definitive deterioration is defined as a decrease in the sub scale score by at least 10% compared with baseline.
Safety and Tolerability of Buparlisib in combination with Paclitaxel compared with Paclitaxel alone as Measured by Number of Participants Experiencing Adverse Events (AEs).	From screening until 4 weeks following treatment discontinuation	Treatment Emergent Adverse Events AEs will be assessed according to the NCI-CTCAE version 5.0 for severity and will be recorded and classified on the basis of MedDRA terminology.; Anxiety score change from baseline taken at time of screening (General Anxiety Disorder 7 item scale) until end of treatment.; Depression score change from baseline taken at time of screening (Patient Health Questionnaire 9) until end of treatment.
Pharmacokinetics of Buparlisib: plasma concentration-time profile of Buparlisib during 15 days of treatment	Day 0 to Day 15 sparse sampling	For Sparse PK sampling, blood samples will be collected on Treatment Cycle 1, Days 1, 8, and 15 at pre-dose, 1 (± 0.25), 2 ± (0.25) and 6 ± (0.5) hours post-dose. PK sampling will be collected only for those patients randomized to the buparlisib in combination with paclitaxel arm and pharmacokinetic profile of Buparlisib combined with paclitaxel in the study population will be compared with a simulated population PK model.

Trial Locations

Locations (162)

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Northwestern University; 🇺🇸 Chicago, Illinois, United States

University of Cincinnati Cancer Center; 🇺🇸 Cincinnati, Ohio, United States

Clinique CHC MontLégia; 🇧🇪 Liege, Belgium

Clinique Saint-Pierre dOttignies CSPO; 🇧🇪 Ottignies, Belgium

Beijing Tongren Hospital; 🇨🇳 Beijing, China

Hunan Cancer Hospital; 🇨🇳 Changsha, China

Xiangya Hospital Central South University; 🇨🇳 Changsha, China

Sichuan Cancer Hospital; 🇨🇳 Chengdu, China

Affiliated Cancer Hospital of Guangzhou Medical University; 🇨🇳 Guangzhou, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, China

Cancer Hospital affiliated to Guangxi Medical University; 🇨🇳 Naning, China

Shanghai Dongfang Hospital; 🇨🇳 Shanghai, China

Tianjin Cancer Hospital; 🇨🇳 Tianjin, China

Henan Cancer Hospital; 🇨🇳 Zhengzhou, China

IRCCS Maugeri Pavia; 🇮🇹 Pavia, Italy

Azienda Ospedaliera Universitaria Integrata Verona; 🇮🇹 Verona, Italy

IONC SRL- Instituto Oncológico de Córdoba; 🇦🇷 Córdoba, Argentina

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

The First Affiliated Hospital of Bengbu Medical College; 🇨🇳 Bengbu, China

City of Hope; 🇺🇸 Duarte, California, United States

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, China

Institut regional du Cancer de Montpellier; 🇫🇷 Montpellier, France

Universitaetsklinikum Bonn; 🇩🇪 Bonn, Germany

NYU Langone; 🇺🇸 New York, New York, United States

Moffitt Cancer Center; 🇺🇸 Tampa, Florida, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Centro de Investigacion Pergamino SA - Clinica Pergamino S.A.; 🇦🇷 Buenos Aires, Argentina

Instituto de Investigaciones Metabólicas (IDIM) // Instituto de Investigaciones Metabólicas S.A.; 🇦🇷 Ciudad Autonoma de Buenos Aire, Argentina

CancerCare Manitoba; 🇨🇦 Winnipeg, Canada

Clinique Hartmann; 🇫🇷 Neuilly Sur Seine, France

Azienda Ospedaliero Universitaria Careggi - Firenze; 🇮🇹 Firenze, Italy

University of Pecs Department of Oncotherapy; 🇭🇺 Pécs, Hungary

Hollings Cancer Center; 🇺🇸 Charleston, South Carolina, United States

Fundacion Cenit para la Investigacion en Neurociencias; 🇦🇷 Buenos Aires, Argentina

Shandong Provincial Tumor Hospital; 🇨🇳 Jinan, China

The Fifth Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Zhuhai, China

Universitair Ziekenhuis Gent UZ Gent; 🇧🇪 Ghent, Belgium

Universitair Ziekenhuis Brussel; 🇧🇪 Jette, Belgium

Hopital de la Timone; 🇫🇷 Marseille, France

The First Affiliated Hospital of CQMU; 🇨🇳 Chongqing, China

Hôpital St-Louis; 🇫🇷 Paris, France

Universitatsklinikum Hamburg Eppendorf; 🇩🇪 Hamburg, Germany

Marienkrankenhaus Hamburg; 🇩🇪 Hamburg, Germany

Universitatsmedizin Greifswald - KoR; 🇩🇪 Greifswald, Germany

Universitatsklinikum Leipzig; 🇩🇪 Leipzig, Germany

Orszagos Onkologiai Intezet; 🇭🇺 Budapest, Hungary

Tolna Megyei Balassa Janos Korhaz; 🇭🇺 Szekszárd, Hungary

Azienda Ospedaliera Universitaria S.Orsola-Malpighi; 🇮🇹 Bologna, Italy

Istituto di Candiolo IRCCS; 🇮🇹 Candiolo, Italy

Azienda Sanitaria Universitaria Integrata di Udine; 🇮🇹 Udine, Italy

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie; 🇵🇱 Warszawa, Poland

Korea University Guro Hospital; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Hospital Clinico Universitario Virgen de la Arrixaca; 🇪🇸 Madrid, Spain

Hospital Universitario Miguel Servet; 🇪🇸 Zaragoza, Spain

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Ajou University Hospital; 🇰🇷 Suwon-si, Korea, Republic of

Stony Brook University Medical Center; 🇺🇸 Stony Brook, New York, United States

Fundacion CORI para la Investigacion y Prevencion del Cáncer; 🇦🇷 La Rioja, Argentina

Emory University; 🇺🇸 Atlanta, Georgia, United States

Yunnan Cancer Hospital; 🇨🇳 Kunming, China

Yale University, Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Hope Cancer Center, UT Health East Texas; 🇺🇸 Tyler, Texas, United States

Centro para la Atencion Integral del Paciente Oncologico - CAIPO; 🇦🇷 Tucuman, Argentina

Princess Alexandra Hospital; 🇦🇺 Brisbane, Australia

CHUM; 🇨🇦 Montreal, Canada

Affiliated Cancer Hospital of Chongqing University; 🇨🇳 Chongqing, China

Anhui Provincial Cancer Hospital; 🇨🇳 Hefei, China

Centre Leon Berard; 🇫🇷 Lyon, France

Centre hospitalier Universitaire de Bordeaux; 🇫🇷 Bordeaux, France

Centre Franois Baclesse; 🇫🇷 Caen, France

LHopital prive du Confluent Nantes; 🇫🇷 Nantes, France

Hopital Tenon; 🇫🇷 Paris, France

CHP Saint-Grégoire; 🇫🇷 Saint-Grégoire, France

Hopital La Pitie Salpetriere; 🇫🇷 Paris, France

Institut de cancerologie de Lorraine; 🇫🇷 Vandœuvre-lès-Nancy, France

Uniklinik RWTH Aachen; 🇩🇪 Aachen, Germany

Franziskus Hospital; 🇩🇪 Georgsmarienhütte, Germany

HNO-Klinik des Universitats-Klinikums Giessen; 🇩🇪 Giessen, Germany

University Hospital Essen; 🇩🇪 Essen, Germany

Hannover Medical School; 🇩🇪 Hannover, Germany

UNIVERSITÄTSMEDIZIN Mainz III. Klinik/Poliklinik; 🇩🇪 Mainz, Germany

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong

ASST Spedali Civili Brescia; 🇮🇹 Brescia, Italy

IRCCS - Istituto Scientifico Romagnolo per la Cura e lo Studio dei Tumori; 🇮🇹 Cesena, Italy

A.O. S. Croce e Carle; 🇮🇹 Cuneo, Italy

Azienda Ospedaliera San Paolo Polo Universitario; 🇮🇹 Milano, Italy

INT IRCCS Fondazione G.Pascale; 🇮🇹 Napoli, Italy

Istituto Nazionale dei Tumori; 🇮🇹 Milan, Italy

A.O.U. "Maggiore della Carita"- S.C.D.U Oncologiac; 🇮🇹 Novara, Italy

Azienda Ospedaliero Universitaria di Parma; 🇮🇹 Parma, Italy

AOU San Giovanni di Dio e Ruggi D'Aragona, Università degli Studi di Salerno; 🇮🇹 Salerno, Italy

Azienda Ospedaliero Universitaria Policlinico "Paolo Giaccone" U.O.C. Oncologia Medica; 🇮🇹 Palermo, Italy

IRCCS Istituto Clinico Humanitas; 🇮🇹 Rozzano, Italy

Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte; 🇮🇹 Siena, Italy

AO Card. G. Panico; 🇮🇹 Tricase, Italy

ASST Valtellina e Alto Lario - UOC Oncologia Medica Ospedale di Sondrio; 🇮🇹 Sondrio, Italy

Hyogo Cancer Center; 🇯🇵 Akashi-shi, Japan

Kagawa University Hospital; 🇯🇵 Kita-gun, Japan

Saitama Medical University International Medical Center; 🇯🇵 Hidaka, Japan

National Cancer Center Hospital; 🇯🇵 Chuo Ku, Japan

Kobe University Hospital; 🇯🇵 Kobe, Japan

Kyushu University Hospital; 🇯🇵 Fukuoka shi, Japan

Aichi Cancer Center; 🇯🇵 Nagoya, Japan

The Cancer Institute Hospital of JFCR; 🇯🇵 Koto-Ku, Japan

Kindai University Hospital; 🇯🇵 Osaka Sayama-shi, Japan

National Hospital Organization Shikoku Cancer Center; 🇯🇵 Matsuyama, Japan

Hokkaido University Hospital; 🇯🇵 Sapporo, Japan

National University Corporation Tohoku University, Tohoku University Hospital; 🇯🇵 Sendai, Japan

Kosin University Gospel Hospital; 🇰🇷 Busan, Korea, Republic of

Gachon University Gil Medical Center; 🇰🇷 Incheon, Korea, Republic of

Showa University Hospital; 🇯🇵 Shinagawa-Ku, Japan

Shizuoka Cancer Center; 🇯🇵 Shizuoka, Japan

Korea University Anam Hospital; 🇰🇷 Seoul, Korea, Republic of

Seoul National University Bundang Hospital; 🇰🇷 Seongnam-si, Korea, Republic of

The Catholic University of Korea Seoul ST. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

Fundacion Oncologico de Galicia Jos Antonio Quiroga y Pieyro; 🇪🇸 A Coruña, Spain

Hospital Clinic Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitario de Burgos; 🇪🇸 Burgos, Spain

Vall dHebron Institute of Oncology (VHIO); 🇪🇸 Barcelona, Spain

Institut Catala d Oncologia Badalona; 🇪🇸 Badalona, Spain

Hospital Reina Sofia; 🇪🇸 Córdoba, Spain

Complejo Hospitalario de Jaen; 🇪🇸 Jaén, Spain

Hospital Duran i Reynals - Institut Catala dOncologia ICO; 🇪🇸 Hospitalet de Llobregat, Spain

Hospital Universitario Severo Ochoa; 🇪🇸 Leganés, Spain

Clinica Universidad de Navarra; 🇪🇸 Madrid, Spain

Hospital Universitario Lucus Augusti; 🇪🇸 Lugo, Spain

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario Fundacion Jimenez Diaz; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital General Universitario Gregorio Maran; 🇪🇸 Madrid, Spain

Hospital Puerta de Hierro- Majadahonda; 🇪🇸 Majadahonda, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Regional de Malaga; 🇪🇸 Málaga, Spain

Hospital de Navarra; 🇪🇸 Pamplona, Spain

Hospital Universitario Marques de Valdecilla; 🇪🇸 Santander, Spain

Hospital Universitario Santiago de Compostela; 🇪🇸 Santiago De Compostela, Spain

Valme Hospital Medical Oncology Department; 🇪🇸 Sevilla, Spain

Chang Gung Memorial Hospital-KaohSiung; 🇨🇳 Kaohsiung, Taiwan

Hospital Clinico Universitario Valencia - INCLIVA; 🇪🇸 Valencia, Spain

Instituto Valenciano de Oncologia; 🇪🇸 Valencia, Spain

Taipei Veterans General Hospital; 🇨🇳 Taipei, Taiwan

Chang Gung Memorial Hospital-LinKou; 🇨🇳 Taoyuan, Taiwan

Beatson Oncology Centre; 🇬🇧 Glasgow, United Kingdom

University College London Hospitals; 🇬🇧 London, United Kingdom

The Royal Marsden NHS Foundation Trust; 🇬🇧 London, United Kingdom

Edinburgh Cancer Center; 🇬🇧 Edinburgh, United Kingdom

The Royal Marsden NHS Foundation Trust - Sutton; 🇬🇧 Sutton, United Kingdom

Changhua Christian Hospital; 🇨🇳 Changhua, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

Chi Mei Medical Center Liouying; 🇨🇳 Tainan, Taiwan

National Cheng Kung University Hospital; 🇨🇳 Tainan, Taiwan

Fox Chase Cancer Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie; 🇵🇱 Gliwice, Poland

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

West Cancer Center; 🇺🇸 Germantown, Tennessee, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States