MDX-010 Antibody, MDX-1379 Melanoma Vaccine, or MDX-010/MDX-1379 Combination Treatment for Patients With Unresectable or Metastatic Melanoma
- Conditions
- MelanomaMetastases
- Interventions
- Biological: MDX-1379 (gp100) Melanoma Peptide VaccineDrug: MDX-010 (anti-CTLA4) monoclonal antibody
- Registration Number
- NCT00094653
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to determine the safety and efficacy of MDX-010 (ipilimumab, BMS-734016) (anti-CTLA4) in combination with MDX-1379 (gp100, BMS-734019) in patients with previously treated, unresectable Stage III or IV melanoma. Survival time will be evaluated, as well as patient responses and time to disease progression. Eligible patients are those who in response to a single regimen containing interleukin-2 (IL-2), dacarbazine, and/or temozolomide, have 1) relapsed following an objective response (partial response/complete response \[PR/CR\]); 2) failed to demonstrate an objective response (PR/CR); or 3) could not tolerate such a regimen due to unacceptable toxicity. Patients will be randomized into one of three groups, and will receive one of the following treatments: MDX-010 alone, MDX-1379 alone, or MDX-010 in combination with MDX-1379.
- Detailed Description
Melanoma accounts for approximately 5% of all skin cancers in the United States, but it accounts for about 75% of all skin cancer deaths. In 2004, the expected prevalence of melanoma is 627,252, with about 119,178 of these cases being Stage III or IV (metastatic melanoma). First line treatments for metastatic melanoma, usually IL-2, dacarbazine and/or temozolomide, are associated with significant toxicities. MDX-010 (anti-CTLA4) antibodies are designed to keep the immune system running by blocking CTLA-4 from down-regulating T cell activation. MDX-1379 is made up of two peptides that are pieces of a bigger melanoma protein (gp100). These peptides bind to HLA-A2 which is then recognized by T cells.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1783
- Diagnosed with malignant melanoma
- Measurable unresectable Stage III or IV melanoma
- HLA-A*0201 positive
- Previous treatment with & failure/relapse/inability to tolerate IL-2, dacarbazine and/or temozolomide
- At least 4 weeks since prior treatment
- Negative pregnancy
- Life expectancy greater than 4 months
- Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1
- Required lab values
- Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) negative
- Prior malignancies which the patient has not been disease free for over 5 years, except treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any other cancer
- Ocular melanoma
- Active, untreated central nervous system (CNS) metastasis
- Prior treatment with MDX-010 (anti-CTLA4) antibody
- Prior treatment with any cancer therapeutic vaccine
- Active autoimmune disease or history of autoimmune disease
- Pregnancy or nursing
- Hypersensitivity to Incomplete Freund's Adjuvant (IFA) (Montanide ISA-51)
- Underlying medical conditions deemed hazardous if treated with study drug
- Concomitant therapy with anti-melanoma drugs, chemotherapies, other investigational therapies, chronic use of systemic corticosteroids
- Unable to provide informed consent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 MDX-1379 (gp100) Melanoma Peptide Vaccine Melanoma Peptide Vaccine (MDX-1379) (gp100) + Placebo 2 MDX-010 (anti-CTLA4) monoclonal antibody MDX-010 (ipilimumab) + MDX-1379 (gp100) (Melanoma Peptide Vaccine) 2 MDX-1379 (gp100) Melanoma Peptide Vaccine MDX-010 (ipilimumab) + MDX-1379 (gp100) (Melanoma Peptide Vaccine) 3 MDX-010 (anti-CTLA4) monoclonal antibody MDX-010 (ipilimumab) + Placebo
- Primary Outcome Measures
Name Time Method Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 in Combination With gp 100 Melanoma Peptide Vaccine Versus gp 100 Melanoma Peptide Vaccine Alone From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks) OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) (Time-to-Death) Difference Between MDX-010 Monotherapy Versus gp100 Melanoma Peptide Vaccine Alone and MDX-010 in Combination With gp100 Melanoma Peptide Vaccine Versus MDX-010 Monotherapy From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks) OS was defined as the time from randomization until death from any cause. If a participant did not expire, the subject was censored at the time of last contact (last known alive date). 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
12-, 18-, and 24-Month Survival Rates Month 12, Month 18, Month 24 The probability that a subject is alive at 12 months, 18 months, and 24 months following randomization, estimated via the non-parametric method (Kaplan-Meier method). For calculating 95% CI, bootstrap method was used with 20000 simulated trials.
Progression Free Survival (PFS) From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks) PFS was defined as the number of days between the date of randomization and the date of the progression or the date of death. A subject who died without prior progression was considered to have progressed on the date of death. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
Percentage of Participants With Progression Free Survival (PFS) at Week 12 and Week 24 Week 12, Week 24 PFS at Week 12 was defined as the probability that the subject was progression-free at 12 weeks and 24 weeks following the start of randomization. It was computed via Kaplan-Meier method, truncated at Week 12 and Week 24. PFS was determined by investigator. 95% confidence intervals (CI) for median were computed using Brookmeyer and Crowley method.
Time to Progression (TTP) from time of randomization to date of PD or death due to PD (end of the study was defined as the time at which 481 deaths were observed [264 weeks]) TTP was defined as the number of days between the date of the randomization and date of PD or death due to PD. For subjects who had not progression and remained alive, TTP was censored on the date of last assessment; those who remained alive and had no recorded post-baseline assessment, TTP was censored on the date of randomization; those who remained alive and had randomized but were not treated, TTP was censored at the date of randomization; for those who died without reported disease progression, TTP was censored on the date of death.
Best Overall Response (BOR): Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressed Disease (PD) BOR was determined between Weeks 12 and Week 24 confirmation at least 4 weeks later at Cycle 1. Investigator's assessment, modified World Health Organization criteria. CR: disappearance of all lesions by 2 consecutive observations \>=4 weeks apart, no evidence of PD. PR: \>=50% ↓ in sum of products of longest diameter \& greatest perpendicular diameter of all target lesions compared to baseline by 2 observations \>=4 weeks apart. SD: Neither sufficient ↓ to qualify for PR nor sufficient ↑ to qualify for PD. PD: ↑ \>=25% in sum of products of longest diameter \& greatest perpendicular diameter of target lesions compared to smallest recorded sum during study, or appearance of \>= 1 new lesion.
Determination of Best Overall Response Rate (BORR) Up to week 24 Response was based on the investigators' assessment using modified WHO criteria. BORR is defined as the number of subjects whose BOR is complete or partial response (CR or PR) divided by the total number of subjects in the group. BORR was comprised of responder and non-responder. The definition of a responder in BORR was either confirmed CR or PR, and a non-responder was defined as stable disease (SD), progressed disease (PD), unconfirmed CR (uCR), unconfirmed PR (uPR), and not evaluated.
Time to Response From randomization until the end of the study, which was defined as the time at which 481 deaths were observed (264 weeks) Time to response was defined as the number of days from the date of randomization to the date when measurement criteria are met for BOR of CR or PR, as determined by investigator.
Duration of Response from time of initial drug administration to date of PD or death due to PD (the end of the study was defined as the time at which 481 deaths were observed [264 weeks]) Kaplan-Meier medians along with Brookmeyer and Crowley 95% confidence intervals (CI) for were computed. Duration of response was defined in subjects whose BOR was CR or PR as the number of days between the date of response (CR or PR) and the date of PD or the date of death (whichever occurs first).
Disease Control Rate (DCR) Up to week 24 Response was based on the investigators' assessment using modified WHO criteria. DCR is defined as the number of subjects whose BOR is CR, PR, or SD divided by the total number of subjects in the group.
Delayed Response (Response Beyond Week 24) from Week 24 to end of study (the end of the study was defined as the time at which 481 deaths were observed [264 weeks]) Response was based on the investigators' assessment using modified World Health Organization (WHO) criteria. Delayed response is defined as post Week 24 overall response for the subjects who have PD before or at Week 24. Evaluation of delayed overall response is compared to baseline assessment. Delayed response includes delayed late CR, delayed late PR, delayed late SD, continued PD, unknown, and missing after Week 24. The delayed response of CR and PR also must have been confirmed.
Change From Baseline in Health-Related Quality of Life (QOL) as Measured by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) Instrument at Week 12 Baseline (Day 1, Cycle1), Week 12 The 30 items were grouped into the following: 1 global QOL scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). All scores were linearly transformed to a 0 to 100 scale. For global QOL and functional items, a higher score represents a better level of functioning (100=best/0=worst). For symptom items, a higher score represents a higher level of symptoms (0=no symptom at all/100=very much severe).
Percentage of Participants With On-Study Adverse Events (AEs) and AEs With an Outcome of Death On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]). An AE was defined as any undesirable sign, symptom, clinically significant laboratory abnormality, or medical condition occurring after starting study treatment, even if the event was not considered to be treatment-related. Adverse events are graded using the Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. If CTCAE grading does not exist for an adverse event, the intensity of mild (1), moderate (2), severe (3), and life-threatening (4) were used.
Percentage of Participants With Immune-Related Adverse Events (irAEs) On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]). An immune related adverse event (irAE) was defined as an adverse event of unknown etiology, associated with study drug exposure and consistent with an immune phenomenon. The irAEs were programmatically determined from a predefined list of MedDRA version 12.0 high-level group terms, high-level terms and preferred terms of all ipilimumab related adverse event. The category of "Other irAEs" includes blood, eye, immune, infections, renal, and respiratory systems.
Percentage of Participants With Worst On-Study Hematological Abnormalities On-study laboratory results are results reported after the first dose date and within 70 days of last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]). ANC=Absolute Neutrophil Count. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.
Percentage of Participants With Worst On-Study Liver Abnormalities On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]). ALT=alanine aminotransferase; AST=aspartate aminotransferase. CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.
Percentage of Participants With Worst On-Study Renal Abnormalities On-study adverse events include all AEs reported between the first dose and 70 days after the last dose of study therapy (end of the study was defined as the time at which 481 deaths were observed [264 weeks]). CTCAE v3.0 Grades 0 through 4 of severity for each AE based on this general guideline: Grade 0=Normal, Grade 1=Mild AE, Grade 2=Moderate AE, Grade 3=Severe AE, Grade 4=Life-threatening or disabling AE.
Clinically Meaningful Changes in Vital Signs and Physical Examinations vital signs and physical examination were evaluated at screening and at Weeks 1, 4, 7, 10, 12, 16, 20, 24, 28, 36, and every 3 months thereafter Clinically meaningful changes were according to investigator. Vital sign measurements include height, weight, temperature, pulse, and resting systolic and diastolic blood pressure.
Trial Locations
- Locations (183)
USC/Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
The Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Jackson Memorial Hospital & Clinics
🇺🇸Miami, Florida, United States
Indiana Oncology Hematology Consultants North
🇺🇸Indianapolis, Indiana, United States
American Health Network of IN, LLC
🇺🇸Indianapolis, Indiana, United States
Indiana Oncology Hematology South
🇺🇸Indianapolis, Indiana, United States
The Christ Hospital Cancer Center
🇺🇸Cincinnati, Ohio, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Hospital de Cancer de Barretos - Fundacao Pio XII
🇧🇷Barretos - SP, Brazil
Southampton General
🇬🇧Southampton, United Kingdom
Klinikum Mannheim gGmbH
🇩🇪Mannheim, Germany
Hospital Araujo Jorge
🇧🇷Goiania - GO, Brazil
Fundacoa Hospital Amaral Carvalho
🇧🇷Jau, SP, Brazil
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Klinikum Augsburg
🇩🇪Augsburg, Germany
Fundacao Central Sul-Americana para o Desenvolvimento de Drogas Anticancer-SOAD
🇧🇷Porto Alegre, Brazil
Universitaetsklinikum Dusseldorf
🇩🇪Duesseldorf, Germany
Sociedade Beneficante de Sennores - Hospital Sino Libante
🇧🇷Sao Paulo, SP, Brazil
Cancer Centre of Southeastern Ontario at KGH
🇨🇦Kingston, Ontario, Canada
Biocor - Hosp. de Doencas Cardiovasculares Ltda.
🇧🇷Belo Horizonte - MG, Brazil
GVI Oncology
🇿🇦Panorama, South Africa
Fund. SOAD / HC de Porto Alegre
🇧🇷Porto Alegre - RS, Brazil
The Ottawa Hospital Regional Cancer Centre
🇨🇦Ottawa, Ontario, Canada
Ninewells Hospital
🇬🇧Dundee, United Kingdom
Institut Gustave Roussy (IGR)
🇫🇷Villejuif, France
Universitaetsklinikum Essen
🇩🇪Essen, Germany
Centre Leon Berard
🇫🇷Lyon, France
Universitaetsklinikum Wuerzburg
🇩🇪Wuerzburg, Germany
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Santo Andre Diagnosticos aTratamentos
🇧🇷Santo Andre, SP, Brazil
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Velindre Hospital
🇬🇧Cardiff, United Kingdom
Hopital Saint-Eloi
🇫🇷Montpellier, France
Sandton Onocology Medical Research
🇿🇦Sandton, South Africa
Pro Onco Centro Tratemento Oncologico
🇧🇷Londrina - PR, Brazil
Hopital Sainte-Marguerite
🇫🇷Marseille, France
Hotel Dieu
🇫🇷Nantes, France
Centre Antoine Lacassagne
🇫🇷Nice cedex 2, France
Santo Andre Diagnosticos e Tratamentos Ltda.
🇧🇷Santo Andre-SP, Brazil
Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada
Klinik fur und Poliklinik fur Dermatologie, Venerologie und Allergologie
🇩🇪Hufelandstr. 55, Essen, Germany
HC-FMUSP
🇧🇷Sao Paulo - SP, Brazil
Charite Universitaets medizin Berlin
🇩🇪Berlin, Germany
Hospital Sao Lucas - PUCRS
🇧🇷Porto Alegre - RS, Brazil
University of Mannheim
🇩🇪Mannheim, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Germany
Universitaetsklinikum Erlangen
🇩🇪Erlangen, Germany
St. Luke's Cancer Center, The Royal Surrey County Hospital
🇬🇧Guildford, Surry, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom
Klinikum der Friedrich-Schiller-Universitaet Jena
🇩🇪Jena, Germany
Klinikum Rechts der Isar / TU Muenchen
🇩🇪Muenchen, Germany
Mary Potter Oncology Centre
🇿🇦Pretoria, South Africa
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Churchill Hospital
🇬🇧Oxford, United Kingdom
Hospital Sirio Labanes
🇧🇷Sao Paulo-SP, Brazil
Dr. H. Bliss Murphy Cancer Centre
🇨🇦St. John's, Newfoundland and Labrador, Canada
Clinica Davila
🇨🇱Recoleta, Santiago, Chile
Centre Hospitalier Universitaire Vaudois - CHUV
🇨🇭Lausanne, Switzerland
University of Debrecen, Medical and Health Sciences Center
🇭🇺Debrecen, Hungary
Vrije Universiteit Medisch Centrum (VUMC)
🇳🇱Amsterdam, Netherlands
Sir Mortimer B. Davis - Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
London Regional Cancer Program
🇨🇦London, Ontario, Canada
Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin
🇩🇪Berlin, Germany
National Institute of Oncology
🇭🇺Budapest, Hungary
Christie Hospital
🇬🇧Manchester, United Kingdom
Arizona Cancer Center
🇺🇸Tucson, Arizona, United States
San Diego Cancer Center
🇺🇸Vista, California, United States
University Medical Center
🇺🇸Tucson, Arizona, United States
Moores UCSD Cancer Center
🇺🇸La Jolla, California, United States
La Jolla Hematology and Oncology Medical Group
🇺🇸La Jolla, California, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Cancer Institute Medical Group, Inc
🇺🇸Santa Monica, California, United States
North County Oncology Medical Clinical, Inc.
🇺🇸Oceanside, California, United States
Scripps Cancer Center
🇺🇸La Jolla, California, United States
Pacific Shores Medical Group
🇺🇸Long Beach, California, United States
City of Hope Medical Group
🇺🇸Pasadena, California, United States
University of California, San Diego
🇺🇸San Diego, California, United States
St. Mary's Medical Center - Northern California Melanoma Center
🇺🇸San Francisco, California, United States
Rocky Mountain Cancer Centers
🇺🇸Longmont, Colorado, United States
Mount Sinai Comprehensive Cancer Center at Aventura
🇺🇸Aventura, Florida, United States
Memorial Regional Cancer Center
🇺🇸Hollywood, Florida, United States
Shands Jacksonville
🇺🇸Jacksonville, Florida, United States
University of Florida/Jacksonville Faculty Clinic
🇺🇸Jacksonville, Florida, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Mount Sinai Medical Center
🇺🇸Miami Beach, Florida, United States
University of Miami Hospital & Clinics
🇺🇸Miami, Florida, United States
Palm Beach Cancer Institute
🇺🇸West Palm Beach, Florida, United States
Emory University Hospital-Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Cancer Care Specialists of Central IL
🇺🇸Effingham, Illinois, United States
Decatur Memorial Hospital
🇺🇸Decatur, Illinois, United States
Cardinal Bernardin Cancer Center, Loyola Unv. Med. Ctr.
🇺🇸Maywood, Illinois, United States
Center for Cancer Care at Goshen Health System
🇺🇸Goshen, Indiana, United States
Indiana Oncology Hematology Consutants of Noblesville
🇺🇸Noblesville, Indiana, United States
Central Baptist Hospital
🇺🇸Lexington, Kentucky, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Lutherville, Maryland, United States
Franklin Square Hospital Center
🇺🇸Baltimore, Maryland, United States
Beth Isreal Dec Medical Center
🇺🇸Boston, Massachusetts, United States
Brigham and Womens Hospital
🇺🇸Boston, Massachusetts, United States
Henry Ford Medical Center- West Bloomfield
🇺🇸West Bloomfield, Michigan, United States
Henry Ford Medical Center
🇺🇸Dearborn, Michigan, United States
Humphrey Cancer Center
🇺🇸Fridley, Minnesota, United States
Barnes Jewish Hospital
🇺🇸St. Louis, Missouri, United States
Ellis Fischel Cancer Center
🇺🇸Columbia, Missouri, United States
Family Cancer Center
🇺🇸Memphis, Tennessee, United States
Washington Unv. School of Med./ Siteman Cancer Center
🇺🇸St. Louis, Missouri, United States
Hubert H Humphrey Cancer Center
🇺🇸Robbinsdale, Minnesota, United States
The Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
St. Joseph Oncology, Inc
🇺🇸St. Joseph, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Hematology-Oncology Associates of Northern NJ, PA
🇺🇸Morristown, New Jersey, United States
The Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Overlook Oncology Center
🇺🇸Summit, New Jersey, United States
Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
New Mexico Oncology Hematology Consultants, Ltd.
🇺🇸Albuquerque, New Mexico, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Columbia University Medical Center, Irving Center for Clinical Research
🇺🇸New York, New York, United States
Thomas Jefferson University Hosptital
🇺🇸Philadelphia, Pennsylvania, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Hillman Cancer Research Pavilion
🇺🇸Pittsburgh, Pennsylvania, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
University of Pittsburgh Cancer Institute
🇺🇸Pittsburgh, Pennsylvania, United States
The West Clinic
🇺🇸Memphis, Tennessee, United States
Cancer Centers of the Carolinas
🇺🇸Spartanburg, South Carolina, United States
Fletcher Allen Health Care
🇺🇸Burlington, Vermont, United States
Center for Oncology Research and Treatment
🇺🇸Richardson, Texas, United States
Arlington Cancer Center
🇺🇸Arlington, Texas, United States
Joe Arrington Cancer Research and Treatment Center
🇺🇸Lubbock, Texas, United States
Hospital Municipal de Oncoligia Maria Curie
🇦🇷Ciudad de Buenos Aires, Buenos Aires, Argentina
Instituto Medico Especializado Alexander Fleming
🇦🇷Buenos Aires, Argentina
Instituto Medico Platense
🇦🇷La Plata, Provincia de Buenos Aires, Argentina
Hospital Britanico de Buenos Aires
🇦🇷Ciudad de Buenos Aires, Argentina
Hospital Municipal de Oncologia Maria Curie
🇦🇷Ciudad de Buenos Aires, Argentina
Hospital General de Agudos Carlos G. Durand
🇦🇷Ciudad de Buenos Aires, Argentina
Instituto de Oncologia Angel H. Roffo
🇦🇷Ciudad de Buenos Aires, Argentina
Instituto Alexander Fleming
🇦🇷Ciudad de Buenos Aires, Argentina
Hospital Privado de Cordoba S.A.
🇦🇷Cordoba, Argentina
Hospital Privado Centro Medico de Cordoba S.A.
🇦🇷Cordoba, Argentina
ISIS Clinica Especializada
🇦🇷Santa Fe, Argentina
Institut Jules Bordet
🇧🇪Brussels, Belgium
Erasme Hospital, Free Universtiy of Brussels
🇧🇪Brussels, Belgium
Erasme Hospital
🇧🇪Brussels, Belgium
U.Z. Gent
🇧🇪Gent, Belgium
Universitair Ziekenhuis Gasthuisberg
🇧🇪Leuven, Belgium
Pro Onco Centro Tratamento Oncologico
🇧🇷Londrina, PR, Brazil
Fundacao Pio XII - Hospital de Cancer de Barretos
🇧🇷Barretos, SP, Brazil
Hospital Araujo Jorge da Associacoa de Combate ao Cancer em Goias
🇧🇷Goiania, GO, Brazil
Hospital Sao Lucas da PUCRS
🇧🇷Porto Alegre, RS, Brazil
Centre Oscar Lambret
🇫🇷Lille, France
Clinica Renaca
🇨🇱Renaca, Vina Del Mar, Chile
Centre Alexis Vautrin
🇫🇷Vandoeuvre les Nancy, France
Hopital Saint-Louis
🇫🇷Paris, France
Centre Eugene Marquis
🇫🇷Rennes, France
Centre-Hospitalier Universitaire de Saint-Etienne
🇫🇷Saint-Etienne, France
Universitaetsklinikum Heidelberg
🇩🇪Heidelburg, Germany
Poole Hospital
🇬🇧Poole, United Kingdom
Anschutz Cancer Pavilion
🇺🇸Aurora, Colorado, United States
University of Colorado Health Sciences Center
🇺🇸Aurora, Colorado, United States
University of Colorado Hospital
🇺🇸Denver, Colorado, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
The Oregon Clinical
🇺🇸Portland, Oregon, United States
Hematology-Oncology Associates of CNY
🇺🇸East Syracuse, New York, United States
Hospital Barros Luco
🇨🇱Santiago, Chile
Semmelweis Hospital
🇭🇺Miskolc, Hungary
University of Szeged, Albert Szent-Gyorgyi Medical and Pharmaceutical Center
🇭🇺Szeged, Hungary
Cliniques Universitaires UCL de Mont-Godinne
🇧🇪Yvoir, Belgium
Academisch Ziekenhuis Maastricht
🇳🇱Maastricht, Netherlands
Dermatologische Klinik Universitatsspital Zurich
🇨🇭Zurich, Switzerland
Instituto Nacional del Cancer
🇨🇱Independencia, Santiago, Chile
Fundacion Arturo Lopez Perez
🇨🇱Santiago, Chile
Antoni Van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
Yale University School of Medicine - Oncology Outpatient Clinic
🇺🇸New Haven, Connecticut, United States
M.D. Anderson Cancer Center Orlando
🇺🇸Orlando, Florida, United States
James Graham Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Norton Hospital
🇺🇸Louisville, Kentucky, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
University of Louisville Hospital
🇺🇸Louisville, Kentucky, United States
Hospital Militar Central
🇦🇷Ciudad de Buenos Aires, Argentina