Clinical trial NCT04008797: A Study of E7386 in Combination With Other Anticancer Drug(s) in Participants With Solid Tumor
Official title: An Open-label Study of E7386 in Combination With Other Anticancer Drug(s) in Subjects With Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Neoplasms
Carcinoma, Hepatocellular
Liver Neoplasms
Colorectal Neoplasms
Endometrial Neoplasms
Keywords: Solid Tumor
Hepatocellular carcinoma
Endometrial cancer
Colorectal cancer
E7386
Lenvatinib
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-05
Enrollment: 301
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The Dose Optimization part and HCC subpart of Expansion part of the study are randomized. The Dose Escalation part, and CRC/EC subparts of Dose Escalation part are non-randomized.
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to assess the safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with other anticancer drug(s), and to determine the optimal dose of E7386 in combination with lenvatinib in endometrial carcinoma (EC) (for EC Dose Optimization Part only).

Detailed description: The Dose Escalation and Dose Expansion parts of the study have completed enrollment. The Dose Optimization part of the study is enrolling participants with endometrial carcinoma (EC) only.

Eligibility criteria: Inclusion Criteria:

1. HCC part only:

   Participants with confirmed diagnosis of unresectable HCC with any of the following criteria:
   1. Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors
   2. Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology and/or chronic hepatitis B or C infection

   ST part only (except for HCC):

   Participants with histologically or cytologically confirmed diagnosis of solid tumor for which no alternative standard therapy or no effective therapy exists
2. Life expectancy of \>=12 weeks
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
4. All AEs due to previous anti-cancer therapy have either returned to Grade 0 to 1 except for alopecia or up to Grade 2 peripheral neuropathy (renal/bone marrow/liver function should meet the inclusion criteria)
5. Adequate washout period before study drug administration:

   1. Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever is shorter
   2. Any antitumor therapy with antibody: 4 weeks or more
   3. Any investigational drug or device: 4 weeks or more
   4. Blood/platelet transfusion or granulocyte colony-stimulating factor (G-CSF): 2 weeks or more Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not had radiation pneumonitis
6. Adequate controlled blood pressure (BP), renal function, bone marrow function, liver function, and serum mineral level
7. At least one measurable lesion based on mRECIST (for HCC Subparts in Dose Escalation Part) or on RECIST 1.1 (for Other ST Subparts in Dose Escalation Part and all subparts in Expansion and Dose Optimization Parts) meeting following criteria

   * At least 1 lesion of \>=1.0 centimeter (cm) in the longest diameter for a non-lymph node or \>=1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to RECIST 1.1 using computerized tomography (CT)/magnetic resonance imaging (MRI)
   * Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation, or transarterial chemoembolisation (TACE)/ transarterial embolization (TAE) must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
8. For HCC participants only: Child-Pugh score A. Note: If Child-Pugh score 7 or more was observed during Screening or Baseline, the participant is ineligible and re-assessment of the Child-Pugh score is not permitted
9. For HCC participants only: Participants categorized to stage B (not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment), or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system
10. For HCC Subpart in Expansion Part only: prior systemic therapy for locally advanced or metastatic disease is as defined below

    a. Participants who have received only one prior line of immuno oncology (IO) based regimen and have progressed on or after prior treatment with IO based regimen, or IO ineligible participants who have received no prior systemic therapy. Participants who previously received lenvatinib treatment are ineligible
11. For CRC Subpart in Expansion Part only: participants must have received at least 2 prior regimens (not exceeding 4 prior regimens) or could not tolerate standard treatment and must have received the following prior therapies in the metastatic setting if approved and locally available (progressed on at least 1 prior regimen in the metastatic setting or could not tolerate standard treatment):

    Note: Adjuvant chemotherapy counts as prior systemic treatment if there is documented disease progression within 6 months of treatment completion Note: If a participant is determined to be intolerant to prior standard treatment, the participant must have received at least of 2 cycles of that therapy Note: Participants who have received oral tyrosine kinase inhibitor (example, regorafenib) are ineligible
    1. Fluoropyrimidine, irinotecan and oxaliplatin with or without an anti-Vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) (example, bevacizumab) Note: Capecitabine is acceptable as equivalent to fluoropyrimidine in prior treatment Note: Participants who have previously received fluoropyrimidine, oxaliplatin, and irinotecan as part of the same and only chemotherapy regimen, example, FOLFOXIRI or FOLFIRINOX, may be eligible after discussion with the Sponsor
    2. Chemotherapy with anti- epidermal growth factor receptor (EGFR) mAb (cetuximab or panitumumab) for participants with rat sarcoma virus (RAS) (Kirsten rat sarcoma viral oncogene homolog \[KRAS)/ NRAS\]) wild type (WT) CRC Note: RAS (KRAS/NRAS) WT participants with right or left CRC lesions who may have not been treated with anti-EGFR mAb based on local guidelines are eligible
    3. BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600E mutated tumors
    4. Immune checkpoint inhibitor for participants with microsatellite instability-high (MSI-H) CRC
12. For EC Subpart in Expansion Part only: Participants must have EC that has progressed after prior platinum-based chemotherapy and an anti-programmed cell death (ligand) 1 (PD-\[L\])1)-directed therapy for EC (participants ineligible for IO therapy who have progressed after prior platinum-based chemotherapy are eligible). Up to 3 prior systemic therapies, of which up to 2 for metastatic or locally advanced disease, are permitted Note: There is no restriction regarding prior hormonal therapies For Dose Optimization Part only: Participants must have EC that has progressed after prior platinum-based chemotherapy and an anti-PD-(L)1-directed therapy for EC. Up to 3 lines of prior therapy, regardless of setting, are allowed. Note: Prior hormonal therapy and radiation are allowed and do not count as prior lines of therapy.

Exclusion Criteria:

1. Any of cardiac conditions as follows:

   * Heart failure New York Heart Association (NYHA) Class II or above
   * Prolongation of QT interval with Fridericias correction (QTcF) to greater than (\>) 480 millisecond (msec)
   * Left ventricular ejection fraction (LVEF) less than (\<) 50 percent (%)
2. Major surgery within 21 days or minor surgery (that is, simple excision) within 7 days prior to starting study drug. Participant must have recovered from the surgery related toxicities to less than Grade 2 Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility
3. Known to be human immunodeficiency virus (HIV) positive Note: the sponsor has evaluated whether to include participant with HIV. Given that this is the first combination study of E7386 with lenvatinib and that the main mechanism of action of E7386 is immunomodulation of the tumor microenvironment along with the fact that several anti-retroviral therapies have drug-drug interaction with cytochrome P450 3A (CYP3A) substrates, the sponsor has decided not to include these participants at the current time. However, further considerations will be made moving forward based on new emerging data Note: HIV testing is required at screening only when mandated by local health authority
4. Participants with proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein \>=1 gram per 24 hour will be ineligible
5. Active infection requiring systemic treatment (Except for Hepatitis B and/or C \[HBV/HCV\] infection in HCC participants)

   In case of HBsAg (+) participants in HCC participants:
   * Antiviral therapy for HBV is not ongoing
   * HBV viral load is 2000 international unit per milliliter (IU/mL) or more at the Screening Period although antiviral therapy for HBV is ongoing
   * Has dual active HBV infection (HBsAg (+) and/or detectable HBV deoxyribonucleic acid \[DNA\]) and HCV infection (anti-HCV Ab (+) and detectable HCV ribonucleic acid \[RNA\]) at study entry
6. Diagnosed with meningeal carcinomatosis
7. Participants with central nervous system metastases are only eligible if they have been previously treated and are radiologically stable, (that is, without evidence of progression for at least 4 weeks prior to first dose of study treatment by repeat imaging), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
8. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
9. Any of bone disease/conditions as follows:

   * T-score of \< minus (-) 3.0 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by dual energy x-ray absorptiometry (DXA) scan. Participants with T-score \<-2.5 to -3.0 can only be included if treatment with a bisphosphonate (example, zoledronic acid) or denosumab has been started at least 14 days and no more than 6 months prior to the first dose of study drug
   * Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
   * Symptomatic hypercalcemia requiring bisphosphonate therapy
   * History of any fracture within 6 months prior to starting study drug
   * Bone metastasis requiring orthopedic intervention
   * Bone metastasis not being treated by bisphosphonate or denosumab. Participants may be included if treatment with bisphosphonate or denosumab has been started at least 14 days prior to the first dose of study drug. Participants with previous solitary bone lesions controlled with radiotherapy are eligible
   * History of symptomatic vertebral fragility fracture or any fragility fracture of the hip, pelvis, wrist or other location (defined as any fracture without a history of trauma or because of a fall from standing height or less)
   * Moderate (25% to 40% decrease in the height of any vertebrae) or severe (\>40% decrease in the height of any vertebrae) morphometric vertebral fracture at baseline
10. History of malignancy (except for original disease, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ \[example, bladder or cervix\]) within the past 24 months prior to the first dose of study drug
11. For HCC Subpart in Dose Escalation Part only: Participants who experienced discontinuation of lenvatinib, 2 or more dose reductions of lenvatinib required from initial dose level of this study due to its toxicity, or participants who experienced single dose reduction or consecutive \>=8 days dose interruption of lenvatinib within 60 days from the first dose, due to its toxicity. HCC Subpart in Expansion Part only: Participants who previously received lenvatinib treatment are ineligible.

    EC Subpart in Expansion Part only: Participants previously treated with lenvatinib who experienced discontinuation of lenvatinib due to toxicity, or dose reduction to less than 10 mg of lenvatinib due to toxicity within 60 days from the first dose.

    EC Dose Optimization Part only: Participants who previously received lenvatinib treatment are ineligible.
12. Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic International Normalized Ratio (INR) monitoring for HCC participants only (example, warfarin or similar agents). Treatment with low molecular weight heparin and factor X inhibitors is permitted. Treatment with antiplatelet agents is prohibited for HCC participants in Dose Escalation Part only
13. Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug
14. For HCC participants only: History of hepatic encephalopathy within 6 months prior to starting study drug
15. For EC Subpart in Expansion and Dose Optimization Parts only: carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and endometrial stromal sarcomas
16. Has preexisting \>=Grade 3 gastrointestinal or non-gastrointestinal fistula
17. Evidence of current Coronavirus disease 2019 (COVID-19) infection or ongoing unrecovered active sequelae of COVID-19 infection
18. Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (that is, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and after study drug discontinuation). No sperm donation is allowed during the study period and after study drug discontinuation
19. Has a known psychiatric or substance abuse disorder that would interfere with the participant ability to cooperate with the requirements of the study
20. Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator could affect the participant safety or interfere with the study assessments
21. Scheduled for major surgery during the study

Primary outcomes:
measure: Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs)
timeFrame: Cycle 0 (Cycle 0 length=6 or 7 days) up to Cycle 1 (Cycle 1 length=28 days)
measure: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 30 days after the last dose of study drug or before initiating post anti-cancer treatment (up to approximately 60 months)
measure: Dose Optimization Part: Objective Response Rate (ORR) per RECIST 1.1 by Investigator Assessment at Week 24
timeFrame: At Week 24
Secondary outcomes:
measure: Dose Escalation Part: Cmax: Maximum Observed Plasma Concentration for E7386
timeFrame: Day 1 to Day 8
measure: Dose Escalation Part: Cmax: Maximum Observed Plasma Concentration for Lenvatinib
timeFrame: Day 8
measure: Dose Escalation Part: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7386
timeFrame: Day 1 to Day 8
measure: Dose Escalation Part: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Lenvatinib
timeFrame: Day 8
measure: Dose Escalation Part: AUC: Area Under the Plasma Concentration Versus Time Curve for E7386
timeFrame: Day 1 to Day 8
measure: Dose Escalation Part: AUC: Area Under the Plasma Concentration Versus Time Curve for Lenvatinib
timeFrame: Day 8
measure: Dose Escalation Part: CL/F: Apparent Total Body Clearance for E7386
timeFrame: Day 1 to Day 8
measure: Dose Escalation Part: CL/F: Apparent Total Body Clearance for Lenvatinib
timeFrame: Day 8
measure: Dose Escalation Part: Vz/F: Apparent Volume of Distribution for E7386
timeFrame: Day 1 to Day 8
measure: Dose Escalation Part: Vz/F: Apparent Volume of Distribution for Lenvatinib
timeFrame: Day 8
measure: Percentage of Participants with Best Overall Response (BOR)
timeFrame: From first dose of study drug until progression of disease (PD), development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 60 months)
measure: Objective Response Rate (ORR)
timeFrame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 60 months)
measure: Disease Control Rate (DCR)
timeFrame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 60 months)
measure: Clinical Benefit Rate (CBR)
timeFrame: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 60 months)
measure: Progression-free Survival (PFS)
timeFrame: From first dose of study drug until PD, or death from any cause, whichever occurs first (up to approximately 60 months)
measure: Overall Survival (OS)
timeFrame: From first dose of study drug until death from any cause (up to approximately 60 months)
measure: Duration of Response (DOR)
timeFrame: From first dose of study drug until PD, or death from any cause, whichever occurs first (up to approximately 60 months)
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: UAMS
state: Arkansas
city: La Jolla
country: United States
facility: University of California San Diego (UCSD) - Moores Cancer Center(All)
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Pasadena
country: United States
facility: Pasadena Liver Center
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Santa Monica
country: United States
facility: UCLA University of California - Los Angeles
state: California
city: Walnut Creek
country: United States
facility: John Muir Clinical Research
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center - Anschutz Medical Campus
state: Colorado
city: Miami
country: United States
facility: Uni. Of Miami- Sylvester Cancer Centre
state: Florida
city: Sarasota
country: United States
facility: Florida Cancer Specialists - South
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists - East
state: Florida
city: Covington
country: United States
facility: Women's Cancer Care - Covington, LA
state: Louisiana
city: Jackson
country: United States
facility: University Of Mississippi Medical Center
state: Mississippi
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
city: Bronx
country: United States
facility: Montefiore Medical Center (MMC) - Jack D. Weiler Hospital
state: New York
city: New York
country: United States
facility: Perlmutter Cancer Center- NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Sylvania
country: United States
facility: ProMedica Flower Hospital
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Science Center
state: Oklahoma
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Sioux Falls
country: United States
facility: Sanford Cancer Centre
state: South Dakota
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville
state: Tennessee
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson/University of Washington Cancer Consortium
state: Washington
city: Toronto
country: Canada
facility: Sunnybrook Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM, Unit for Innovative Therapies
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Changchun
country: China
facility: Bethune Hospital of Jilin University
city: Fuzhou
country: China
facility: Fujian Provincial Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yan-sen University Cancer Center
city: Guangzhou
country: China
facility: Sun Yat-Sen Memrial Hospital, Sun Yat-Sen University
city: Jinan
country: China
facility: Cancer Hospital of Shandong First Medical University
city: Kunming
country: China
facility: Yunnan Cancer Hospital
city: Shanghai
country: China
facility: Fudan University Cancer Center
city: Shanghai
country: China
facility: The Tenth People's Hospital; Shanghai Tongji University
city: Shenzhen
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center
city: Tianjin
country: China
facility: Tianjin Cancer Hospital
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Odense
country: Denmark
facility: Odense University Hospital
city: Amiens
country: France
facility: CHU Amiens-Picardie (Hopital Sud)
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Brest
country: France
facility: CHU Cavale Blanche
city: Caen
country: France
facility: Centre François Baclesse
city: Clermont-Ferrand
country: France
facility: Centre Jean Perrin
city: Clichy
country: France
facility: Hôpital Beaujon
city: Dijon
country: France
facility: Centre Georges-François Leclerc
city: La Tronche
country: France
facility: Grenoble University Hospital (Centre Hospitalier Universitaire Grenoble Alpes)
city: Lille
country: France
facility: CHU de LILLE - Hôpital HURIEZ
city: Lyon
country: France
facility: Hepatology, Hopital de la Croix-Rousse - 103 grande rue de la Croix-Rousse
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Institut Curie - Centre de Recherche
city: Paris
country: France
facility: APHP Hospital Saint-Antoine
city: Paris
country: France
facility: AP-HP Université de Paris, Port Royal
city: Paris
country: France
facility: Hopital Europeen Georges-Pompidou (HEGP)
city: Paris
country: France
facility: Hopital de la Croix Saint-Simon
city: Pessac
country: France
facility: Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux)(Hopitaux de Bordeaux) - Groupe hospitalier Sud - Hopital Haut-Levequ
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire (CHU) de Poitiers
city: Saint-Herblain
country: France
facility: Insitute de Cancérologie de l'Ouest - Centre René Gauducheau
city: Strasbourg
country: France
facility: ICANs
city: Villejuif
country: France
facility: Gustave Roussy Institute (IGR)
city: Ancona
country: Italy
facility: Clinica Oncologica AOU (Azienda Ospedaliero Universitaria) delle Marche
city: Milan
country: Italy
facility: Istituto Clinico Humanitas, Rozzano
city: Rome
country: Italy
facility: Fondazione Policlinico Gemelli IRCCS
city: Nagoya
country: Japan
facility: Eisai Trial Site #5
state: Aichi
city: Toyoake
country: Japan
facility: Eisai Trial Site #11
state: Aichi
city: Kashiwa
country: Japan
facility: Eisai Trial Site #2
state: Chiba
city: Matsuyama
country: Japan
facility: Eisai Trial Site #8
state: Ehime
city: Kurume
country: Japan
facility: Eisai Trial Site #7
state: Fukuoka
city: Akashi
country: Japan
facility: Eisai site #13
state: Hyogo
city: Kawasaki
country: Japan
facility: Eisai Trial Site #10
state: Kanagawa
city: Kamigyo-ku
country: Japan
facility: Eisai Trial Site #12
state: Kyoto
city: Osakasayama
country: Japan
facility: Eisai Trial Site #3
state: Osaka
city: Hidaka
country: Japan
facility: Eisai Trial Site #9
state: Saitama
city: Chuo-Ku
country: Japan
facility: Eisai Trial Site #1
state: Tokyo
city: Koto-ku
country: Japan
facility: Eisai Trial Site #6
state: Tokyo
city: Minato-ku
country: Japan
facility: Eisai Site 15
state: Tokyo
city: Chiba
country: Japan
facility: Eisai Trial Site #4
city: Niigata
country: Japan
facility: Eisai site #14
city: Seongnamsi Bundang
country: Korea, Republic of
facility: Eisai Trial Site #1
state: Gyeonggi-Do
city: Goyang-si Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
state: Ilsandong-gu
city: Guro-gu
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Seoul
city: Jongno-gu
country: Korea, Republic of
facility: Eisai Trial Site #5
state: Seoul
city: Jongno-gu
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul
city: Seocho-Gu
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
state: Seoul
city: Seodaemun
country: Korea, Republic of
facility: Eisai Trial Site #2
state: Seoul
city: Songpa-Gu
country: Korea, Republic of
facility: Asan Medical Centre
state: Seoul
city: Songpa-gu
country: Korea, Republic of
facility: Eisai Trial Site #4
state: Seoul
city: Seoul
country: Korea, Republic of
facility: Eisai Trial Site #3
city: San Carlos
country: Spain
facility: H. Clinico San Carlos
state: Madrid
city: Barcelona
country: Spain
facility: Fundació Privada Institut d'Investigació Oncològica de Vall-Hebron (VHIO)
city: Coruna
country: Spain
facility: University Hospital A Coruña
city: Jaen
country: Spain
facility: Hospital Universitario de Jaén
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Kao-Hsiung
country: Taiwan
facility: Chang Gung Medical Foundation - Kaohsiung Branch
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Medical Foundation - Linkou Branch
Study officials:
References: