A Study to Evaluate Enfortumab Vedotin Versus (vs) Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301)
- Conditions
- Bladder CancerUreteral CancerUrothelial Cancer
- Interventions
- Registration Number
- NCT03474107
- Lead Sponsor
- Astellas Pharma Global Development, Inc.
- Brief Summary
The purpose of this study was to compare the overall survival (OS) of participants with locally advanced or metastatic urothelial cancer treated with enfortumab vedotin (EV) to the OS of participants treated with chemotherapy.
This study compared progression-free survival on study therapy (PFS1); the overall response rate (ORR) and the disease control rate (DCR) per Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 of participants treated with EV to participants treated with chemotherapy.
In addition, this study evaluated the duration of response (DOR) per RECIST V1.1 of EV and chemotherapy and assessed the safety and tolerability of EV, as well as, the quality of life (QOL) and Patient Reported Outcomes (PRO) parameters.
- Detailed Description
Japan PMDA has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post marketing study in Japan.
Participants considered an adult according to local regulation at the time of obtaining informed consent participated in the study.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 608
-
Subject is legally an adult according to local regulation at the time of signing informed consent.
-
Subject has histologically or cytologically confirmed urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with urothelial carcinoma (transitional cell) with squamous differentiation or mixed cell types are eligible.
-
Subject must have experienced radiographic progression or relapse during or after a checkpoint inhibitor (CPI) (anti-programmed cell death protein 1 (PD1) or anti-programmed death-ligand 1 (PD-L1)) for locally advanced or metastatic disease. Subjects who discontinued CPI treatment due to toxicity are eligible provided that the subjects have evidence of disease progression following discontinuation. The CPI need not be the most recent therapy. Subjects for whom the most recent therapy has been a non-CPI based regimen are eligible if the subjects have progressed/relapsed during or after the subjects most recent therapy. Locally advanced disease must not be amenable to resection with curative intent per the treating physician.
-
Subject must have received a platinum containing regimen (cisplatin or carboplatin) in the metastatic/locally advanced, neoadjuvant or adjuvant setting. If platinum was administered in the adjuvant/neoadjuvant setting subject must have progressed within 12 months of completion.
-
Subject has radiologically documented metastatic or locally advanced disease at baseline.
-
An archival tumor tissue sample should be available for submission to central laboratory prior to study treatment. If an archival tumor tissue sample is not available, a fresh tissue sample should be provided. If a fresh tissue sample cannot be provided due to safety concerns, enrollment into the study must be discussed with the medical monitor.
-
Subject has ECOG PS of 0 or 1
-
The subject has the following baseline laboratory data:
- absolute neutrophil count (ANC) ≥ 1500/mm3
- platelet count ≥ 100 × 10^9/L
- hemoglobin ≥ 9 g/dL
- serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert's disease
- creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards or as measured by 24 hour urine collection (glomerular filtration rate [GFR] can also be used instead of CrCl)
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 3 x ULN for subjects with liver metastases
-
Female subject must either:
- Be of nonchildbearing potential: Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy).
- Or, if of childbearing potential: Agree not to try to become pregnant during the study and for at least 6 months after the final study drug administration, and have a negative urine or serum pregnancy test within 7 days prior to Day 1 (Females with false positive results and documented verification of negative pregnancy status are eligible for participation), and if heterosexually active, agree to consistently use a condom plus 1 form of highly effective birth control per locally accepted standards starting at screening and throughout the study period and for at least 6 months after the final study drug administration.
-
Female subject must agree not to breastfeed or donate ova starting at screening and throughout the study period, and for at least 6 months after the final study drug administration.
-
A sexually active male subject with female partner(s) who is of childbearing potential is eligible if:
- Agrees to use a male condom starting at screening and continue throughout the study treatment and for at least 6 months after final study drug administration. If the male subject has not had a vasectomy or is not sterile as defined below the subjects female partner(s) is utilizing 1 form of highly effective birth control per locally accepted standards starting at screening and continue throughout study treatment and for at least 6 months after the male subject receives final study drug administration.
-
Male subject must not donate sperm starting at screening and throughout the study period, and for at least 6 months after the final study drug administration.
-
Male subject with a pregnant or breastfeeding partner(s) must agree to abstinence or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for at least 6 months after the final study drug administration.
-
Subject agrees not to participate in another interventional study while on treatment in present study.
Inclusion Criteria for COE:
- Subject is eligible for the COE if they continue to meet all inclusion criteria from the main protocol in addition to the following when the patient is evaluated for eligibility to participate in the COE portion of the study:
- Institutional review board (IRB)/ independent ethics committee (IEC) approved written COE informed consent and privacy language as per national regulations (e.g., health insurance portability and accountability act [HIPAA] Authorization for US sites) must be obtained from the subject prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
- Subject was randomized to Arm B and is either currently on study treatment or has discontinued study treatment due to intolerance, AE or progression of disease and has not started a new systemic anticancer treatment.
-
Subject has preexisting sensory or motor neuropathy Grade ≥ 2.
-
Subject has active central nervous system (CNS) metastases. Subjects with treated CNS metastases are permitted on study if all the following are true:
- CNS metastases have been clinically stable for at least 6 weeks prior to screening
- If requiring steroid treatment for CNS metastases, the subject is on a stable dose ≤ 20 mg/day of prednisone or equivalent for at least 2 weeks
- Baseline scans show no evidence of new or enlarged brain metastasis
- Subject does not have leptomeningeal disease
-
Subject has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery). Subject with ≤ Grade 2 immunotherapy-related hypothyroidism or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of hormone replacement therapy (if indicated). Subjects with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or panhypopituitarism are excluded. Subjects with ongoing immunotherapy related colitis, uveitis, or pneumonitis or subjects with other immunotherapy related AEs requiring high doses of steroids (> 20 mg/day of prednisone or equivalent) are excluded.
-
Subject has prior treatment with EV or other monomethyl auristatin E (MMAE)-based Antibody drug conjugates (ADCs).
-
Subject has received prior chemotherapy for urothelial cancer with all available study therapies in the control arm (i.e., both prior paclitaxel and docetaxel in regions where vinflunine is not an approved therapy, or prior paclitaxel, docetaxel and vinflunine in regions where vinflunine is an approved therapy).
-
Subject has received more than 1 prior chemotherapy regimen for locally advanced or metastatic urothelial cancer, including chemotherapy for adjuvant or neo-adjuvant disease if recurrence occurred within 12 months of completing therapy. The substitution of carboplatin for cisplatin does not constitute a new regimen provided no new chemotherapeutic agents were added to the regimen.
-
Subject has history of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Subjects with nonmelanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
-
Subject is currently receiving systemic antimicrobial treatment for viral, bacterial, or fungal infection at the time of first dose of EV. Routine antimicrobial prophylaxis is permitted.
-
Subject has known active Hepatitis B (e.g., hepatitis B surface antigen (HBsAg) reactive) or active hepatitis C (e.g., hepatitis C virus (HCV) Ribonucleic Acid (RNA) [qualitative] is detected).
-
Subject has known history of human immunodeficiency virus (HIV) infection (HIV 1 or 2).
-
Subject has documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of study drug.
-
Subject has radiotherapy or major surgery within 4 weeks prior to first dose of study drug.
-
Subject has had chemotherapy, biologics, investigational agents, and/or antitumor treatment with immunotherapy that is not completed 2 weeks prior to first dose of study drug.
-
Subject has known hypersensitivity to EV or to any excipient contained in the drug formulation of EV; OR subject has known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells.
-
Subject has known hypersensitivity to the following: docetaxel or to any of the other excipients listed in product label, including polysorbate 80, paclitaxel or to any of the other excipients listed in product label, such as macrogolglycerol ricinoleate 35 (Ph.Eur.); and vinflunine or to any of the other excipients listed in product label such as other vinca alkaloids (vinblastine,vincristine, vindesine, vinorelbine).
-
Subject has known active keratitis or corneal ulcerations.
-
Subject has other underlying medical condition that would impair the ability of the subject to receive or tolerate the planned treatment and follow-up.
-
History of uncontrolled diabetes mellitus within 3 months of the first dose of study drug. Uncontrolled diabetes is defined as hemoglobin A1C (HbA1c) ≥ 8% or HbA1c between 7 and < 8% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
Exclusion Criteria for COE
- Subject will be excluded from participation in the COE if they meet any of the exclusion criteria listed in the main protocol or if any of the following apply when the patient is evaluated for eligibility to participate in the COE portion of the study:
- Subject has been diagnosed with a new malignancy while on Arm B in the EV-301 study. Subjects with nonmelanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
- Subject has already started commercial EV or arrangements have been made for subject to start commercial EV which is reimbursed in their country. Additionally, if EV is commercially available with reimbursement in the potential subject's country, the subject can consider transitioning to the commercial product unless otherwise discussed with sponsor.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B: Chemotherapy Vinflunine Participants received either 75 milligrams per square meter (mg/m\^2) docetaxel by IV infusion over approximately 1 hour or 320 mg/m\^2 vinflunine by IV infusion over approximately 20 minutes or 175 mg/m\^2 paclitaxel by IV infusion over approximately 1 hour on day 1 of every 21-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first. Arm A: Enfortumab Vedotin 1.25 mg/kg Enfortumab Vedotin Participants received 1.25 milligrams per kilogram (mg/kg) of body weight enfortumab vedotin by intravenous infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first. Cross-over Extension (COE) Enfortumab Vedotin Eligible participants from chemotherapy arm who met the criteria for COE will receive 1.25 mg/kg of body weight enfortumab vedotin by intravenous infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle until discontinuation criteria is met. Arm B: Chemotherapy Docetaxel Participants received either 75 milligrams per square meter (mg/m\^2) docetaxel by IV infusion over approximately 1 hour or 320 mg/m\^2 vinflunine by IV infusion over approximately 20 minutes or 175 mg/m\^2 paclitaxel by IV infusion over approximately 1 hour on day 1 of every 21-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first. Arm B: Chemotherapy Paclitaxel Participants received either 75 milligrams per square meter (mg/m\^2) docetaxel by IV infusion over approximately 1 hour or 320 mg/m\^2 vinflunine by IV infusion over approximately 20 minutes or 175 mg/m\^2 paclitaxel by IV infusion over approximately 1 hour on day 1 of every 21-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) OS was defined as the time from the date of randomization until the documented date of death from any cause. OS was analyzed using Kaplan-Meier estimates. Participants who were still alive at the time of data cutoff date were to be censored at the last known alive date or at the data cutoff date, whichever was earlier.
- Secondary Outcome Measures
Name Time Method Change From Baseline to Week 12 in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS) Baseline and week 12 EQ-5D-5L is a health status instrument for self-reported assessment of 5 domains of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each domain is rated by selecting 1 of 5 standardized categorizations ranging from no problem to extreme problem. The final question is a visual analogue scale (VAS) to rank health status from 0 (best health imaginable) to 100 (worst health imaginable).
Duration of Response (DOR) as Per RECIST V1.1 From date of first objective response until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) DOR: time from the date of the first CR/PR (whichever is first recorded) that was subsequently confirmed as assessed by investigator to the date of documented PD or death due to any cause whichever occurred first. If a participant has neither progressed nor died, the participant was censored at the date of last RA or at the date of first CR/PR if no subsequent post-baseline RA was available. Participants who received any further ACT for the disease before radiological progression were censored at the date of the last RA before the ACT started. In addition, participants who had PD/death after \>= 2 missed RAs were censored at the last RA prior to the 2 or more missed RAs. Kaplan-Meier estimates was used. Median time of follow up for DOR was based on data cut-off and is same as median follow-up time for OS. CR/PR and PD were defined in ORR and PFS1 endpoints, respectively.
Number of Participants With ECOG Performance Status End of treatment (EOT) (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group) ECOG performance status was measured on an 6 point scale. 0-Fully active, able to carry on all pre-disease performance without restriction.
1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work.
2. Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours.
3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours.
4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.
5. Dead. Number of participants with ECOG PS was reported.Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) PFS: time from date of randomization until date of documented radiological disease progression (PD) per investigator based on RECIST V1.1, or until death due to any cause, whichever occurred first. PD: \>= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of \>= 5 mm. Appearance of 1 or more new lesions is also considered progression. A participant who neither progressed nor died was censored at date of last radiological assessment (RA)/ date of randomization if no post-baseline RA was available. Participants who received any further anticancer therapy (ACT) for disease before radiological progression was censored at date of last RA before ACT started and participants who had PD/death after \>=2 missed RAs were censored at last RA prior to 2 or more missed RAs. Kaplan-Meier estimates was used. Median time of follow-up for PFS was based on data cut-off \& is same as median follow-up time for OS.
Overall Response Rate (ORR) as Per RECIST V1.1 From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) based on the RECIST v1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. ORR was analysed using exact method based on binomial distribution (Clopper-Pearson). Median time of follow up for ORR was based on data cut-off and is same as median follow-up time for OS.
Number of Participants With Treatment Emergent Adverse Events From first dose up to 30 days after last dose (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group) An AE is any untoward medical occurrence in a participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A TEAE is defined as an AE observed or worsened after starting administration of the study drug.
Disease Control Rate (DCR) as Per RECIST V1.1 From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months) DCR was defined as the percentage of participants with a CR, PR or a stable disease (SD) based on RECIST v1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug. Progressive disease is defined in PFS1 endpoint. DCR was analysed using exact method based on binomial distribution (Clopper-Pearson). Median time of follow up for DCR was based on data cut-off and is same as median follow-up time for OS.
Change From Baseline to Week 12 in European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Global Health Status (QL2 Score) Baseline and week 12 EORTC QLQ-C30 is a generic questionnaire consisting of 30 items. The instrument yields functional scales (physical, role, emotional, cognitive, social), symptom scales/items (fatigue, Nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea), global health status, and financial impact score. Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the global health status/QoL, which are scored 1 ("very poor") to 7 ("excellent"). The recall period for each question is "during the past week". All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state. Higher scores on the global health status and functioning scales indicate better health status/function.
Trial Locations
- Locations (158)
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Site BE32013
🇧🇪Brussels, Belgium
Site BE32001
🇧🇪Gent, Belgium
Site BE32005
🇧🇪Hasselt, Belgium
University of Colorado
🇺🇸Denver, Colorado, United States
Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Benaroya Research Institute at Virginia Mason
🇺🇸Seattle, Washington, United States
Site JP81026
🇯🇵Sapporo, Hokkaido, Japan
Site JP81010
🇯🇵Hirosaki, Aomori, Japan
Site JP81024
🇯🇵Takatsuki, Osaka, Japan
Site JP81020
🇯🇵Tsukuba, Ibaraki, Japan
Site JP81001
🇯🇵Kyoto, Japan
Site JP81017
🇯🇵Niigata, Japan
Site JP81021
🇯🇵Tokushima, Japan
Site JP81004
🇯🇵Hiroshima, Japan
Site JP81006
🇯🇵Toyama, Japan
Sidney Kimmel Center for Prostate and Urologic Cancers
🇺🇸New York, New York, United States
HOPE Cancer Center of East Texas
🇺🇸Tyler, Texas, United States
Toledo Clinic Cancer Center
🇺🇸Toledo, Ohio, United States
Site NL31002
🇳🇱Amsterdam, Netherlands
Site NL31009
🇳🇱Nijmegen, Netherlands
Site DK45001
🇩🇰Herlev, Denmark
Site CA15015
🇨🇦Calgary, Canada
Site FR33004
🇫🇷Saint-Mande, France
Site CA15001
🇨🇦Sherbrooke, Canada
Site JP81008
🇯🇵Bunkyo-ku, Tokyo, Japan
Site JP81005
🇯🇵Sendai, Miyagi, Japan
Site FR33002
🇫🇷Strasbourg, France
Site KR82001
🇰🇷Seongnam-si, Korea, Republic of
Site JP81009
🇯🇵Kita-gun, Kagawa, Japan
Site DE49011
🇩🇪Essen, Germany
Site FR33019
🇫🇷Toulouse, France
Site AU61002
🇦🇺Sydney, Australia
Site AT43005
🇦🇹Linz, Austria
Site AT43004
🇦🇹Wien, Austria
Site CA15007
🇨🇦Montreal, Canada
Site CA15013
🇨🇦Vancouver, Canada
Site CA15004
🇨🇦Quebec, Canada
Site CA15002
🇨🇦Montreal, Canada
Site CA15014
🇨🇦London, Canada
Site IT39019
🇮🇹Cremona, Italy
Site IT39010
🇮🇹Milan, Italy
Site FR33009
🇫🇷Bordeaux, France
Site IT39025
🇮🇹Modena, Italy
Site JP81011
🇯🇵Ube, Yamaguchi, Japan
Site JP81023
🇯🇵Fukuoka, Japan
Site DE49009
🇩🇪Würzburg, Germany
Site JP81015
🇯🇵Chiba, Japan
Site DE49010
🇩🇪Münster, Germany
Site FR33001
🇫🇷Brest, France
Site FR33014
🇫🇷Marseille, France
Site FR33003
🇫🇷Nice, France
Site FR33005
🇫🇷Pierre-Bénite, France
Site JP81013
🇯🇵Shinjuku-ku, Tokyo, Japan
Site IT39013
🇮🇹Pisa, Italy
Site JP81018
🇯🇵Morioka, Iwate, Japan
Site IT39014
🇮🇹Reggio Emilia, Italy
Site JP81007
🇯🇵Sapporo, Hokkaido, Japan
Site KR82002
🇰🇷Incheon, Korea, Republic of
Site ES34001
🇪🇸Barcelona, Spain
Site ES34010
🇪🇸Badajoz, Spain
Site RU70002
🇷🇺Ivanovo, Russian Federation
Site KR82006
🇰🇷Daejeon, Korea, Republic of
Site KR82012
🇰🇷Hwasun-gun, Korea, Republic of
Site NL31001
🇳🇱Tilburg, Netherlands
Site KR82004
🇰🇷Seoul, Korea, Republic of
Site KR82005
🇰🇷Shin, Korea, Republic of
Site PT35102
🇵🇹Lisbon, Portugal
Site PT35106
🇵🇹Porto, Portugal
Site GB44013
🇬🇧Sutton, United Kingdom
Site ES34015
🇪🇸Madrid, Spain
Site GB44005
🇬🇧London, United Kingdom
Site TW88606
🇨🇳Taichung, Taiwan
Site ES34002
🇪🇸Badalona, Spain
Site ES34008
🇪🇸Valencia, Spain
Site GB44004
🇬🇧Wirral, United Kingdom
Site FR33022
🇫🇷Paris, France
Site FR33016
🇫🇷Caen, France
Site ES34012
🇪🇸Barcelona, Spain
Site ES34014
🇪🇸Córdoba, Spain
Site ES34013
🇪🇸Madrid, Spain
Site ES34007
🇪🇸Valencia, Spain
Site ES34011
🇪🇸Manresa, Spain
Site ES34017
🇪🇸Madrid, Spain
Site ES34005
🇪🇸Seville, Spain
Site ES34019
🇪🇸Pamplona, Spain
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Site RU70005
🇷🇺Omsk, Russian Federation
Site RU70009
🇷🇺Obninsk, Russian Federation
Site KR82009
🇰🇷Seoul, Korea, Republic of
Site KR82003
🇰🇷Seoul, Korea, Republic of
Site KR82007
🇰🇷Goyang-Si, Korea, Republic of
Site KR82010
🇰🇷Seoul, Korea, Republic of
White Plains Hospital Center for Cancer Care - Oncology Site
🇺🇸White Plains, New York, United States
Providence Portland Med Center
🇺🇸Portland, Oregon, United States
Site ES34023
🇪🇸Barcelona, Spain
UCI Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Innovative Clinical Research
🇺🇸Whittier, California, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Site BE32010
🇧🇪Charleroi, Belgium
Long Island Jewish Medical Center
🇺🇸Lake Success, New York, United States
Lifespan Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Site CA15008
🇨🇦Saskatoon, Canada
Site AU61004
🇦🇺St. Leonards, Australia
Site AR54001
🇦🇷Buenos Aires, Argentina
Site AU61006
🇦🇺Adelaide, Australia
Site AU61001
🇦🇺Miranda, Australia
Site AT43001
🇦🇹Salzburg, Austria
Site BE32007
🇧🇪Brussels, Belgium
Site CA15012
🇨🇦Edmonton, Canada
Site BE32009
🇧🇪Liège, Belgium
Site FR33021
🇫🇷Besancon, France
Site DK45004
🇩🇰Copenhagen, Denmark
Site CA15005
🇨🇦Toronto, Canada
Site DK45003
🇩🇰Aalborg, Denmark
Site FR33018
🇫🇷Bordeaux, France
Site FR33015
🇫🇷Lyon, France
Site FR33006
🇫🇷Villejuif, France
Site DE49003
🇩🇪Tübingen, Germany
Site IT39008
🇮🇹Arezzo, Italy
Site IT39004
🇮🇹Terni, Italy
Site JP81014
🇯🇵Kashiwa, Chiba, Japan
Site JP81016
🇯🇵Osakasayama, Osaka, Japan
Site JP81019
🇯🇵Fukuoka, Japan
Site JP81003
🇯🇵Okayama, Japan
Site JP81022
🇯🇵Osaka, Japan
Site KR82008
🇰🇷Seoul, Korea, Republic of
Site NL31003
🇳🇱Amsterdam, Netherlands
Site RU70015
🇷🇺Vologda, Russian Federation
Site ES34003
🇪🇸Madrid, Spain
Site TW88601
🇨🇳Tainan, Taiwan
Site TW88604
🇨🇳Taipei, Taiwan
Site GB44011
🇬🇧Southampton, United Kingdom
Site TW88605
🇨🇳Kaohsiung, Taiwan
Site CH41002
🇨🇭Bern, Switzerland
Site GB44002
🇬🇧Sheffield, United Kingdom
Site DE49008
🇩🇪Heidelberg, Germany
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Site CA15011
🇨🇦Oshawa, Canada
Site JP81002
🇯🇵Yokohama, Kanagawa, Japan
Site GB44006
🇬🇧London, United Kingdom
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Site JP81012
🇯🇵Koto-ku, Tokyo, Japan
Site CH41001
🇨🇭Chur, Switzerland
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Site PT35105
🇵🇹Lisboa, Portugal
Site TW88602
🇨🇳Kaohsiung, Taiwan
Site TW88607
🇨🇳Taoyuan, Taiwan
Site BE32008
🇧🇪Gent, Belgium
Site BE32011
🇧🇪Aalst, Belgium
Site BE32003
🇧🇪Leuven, Belgium
University of California
🇺🇸Sacramento, California, United States
Smilow Cancer Hospital at Yale-New Haven
🇺🇸New Haven, Connecticut, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Saint Francis Hospital
🇺🇸Greenville, South Carolina, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States