A Study Of Lorlatinib Versus Crizotinib In First Line Treatment Of Patients With ALK-Positive NSCLC
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT03052608
- Lead Sponsor
- Pfizer
- Brief Summary
A phase 3 study to demonstrate whether lorlatinib given as monotherapy is superior to crizotinib alone in prolonging the progression-free survival in advanced ALK-positive NSCLC patients who are treatment naïve and to compare lorlatinib to crizotinib with respect to overall survival in the same population
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 296
- Histologically or cytologically confirmed diagnosis of locally advanced or metastatic ALK-positive NSCLC; at least 1 extracranial measurable target lesion not previously irradiated. CNS metastases allowed if asymptomatic and not currently requiring corticosteroid treatment.
- Availability of an archival FFPE tissue specimen.
- No prior systemic NSCLC treatment.
- ECOG PS 0, 1, or 2.
- Age ≥18 years .
- Adequate Bone Marrow, Liver, Renal, Pancreatic Function
- Negative pregnancy test for females of childbearing potential
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Spinal cord compression unless good pain control attained
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Major surgery within 4 weeks prior to randomization.
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Radiation therapy within 2 weeks prior to randomization, including stereotactic or partial brain irradiation. Whole brain irradiation within 4 weeks prior to randomization
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Active bacterial, fungal, or viral infection
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Clinically significant cardiovascular disease, active or within 3 months prior to enrollment. Ongoing cardiac dysrhythmias, uncontrolled atrial fibrillation, bradycardia or congenital long QT syndrome
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Predisposing characteristics for acute pancreatitis in the last month prior to randomization.
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History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease
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Active malignancy (other than NSCLC, non melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, LCIS/DCIS of the breast, or localized prostate cancer) within the last 3 years prior to randomization.
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Concurrent use of any of the following food or drugs within 12 days prior to the first dose of lorlatinib or crizotinib.
- known strong CYP3A inhibitors .
- known strong CYP3A inducers
- known P gp substrates with a narrow therapeutic index
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Concurrent use of CYP3A substrates with narrow therapeutic indices within 12 days prior to the first dose of lorlatinib or crizotinib.
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Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or interfere with the interpretation of study results
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Investigational site staff members directly involved in the conduct of the study and their family members, or Pfizer employees, including their family members, directly involved in the conduct of the study.
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Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lorlatinib Lorlatinib Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously Crizotinib Crizotinib Crizotinib single agent, 250 mg (1 x 250) oral capsules, BID, continuously
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Based on Blinded Independent Central Review (BICR) Assessment From time of Study Start up to 33 months PFS was defined as the time from randomization to the date of the first documentation of progressive disease as assessed by the independent radiologist or death due to any cause, whichever occurred first. PFS (in months) was calculated as (date of event or censoring-randomization+1)/30.4375. Progressive disease is defined per RECIST version 1.1, as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Based on Investigator's Assessment From time of Study Start up to 33 months PFS was defined as the time from randomization to the date of the first documentation of progressive disease as assessed by investigator or death due to any cause, whichever occurred first. PFS (in months) was calculated as (date of event or censoring-randomization+1)/30.4375. Progressive disease is defined per RECIST version 1.1, as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.
Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on Investigator's Assessment From time of Study Start up to 33 months ORR was the percentage of participants with objective response of complete response (CR) or partial response (PR) according to RECIST version 1.1 recorded from randomization until disease progression or start of new anti-cancer therapy. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). PR was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Intracranial Objective Response Rate (IC-ORR) - Percentage of Participants With Intracranial Objective Response (IC-OR) Based on BICR Assessment From time of Study Start up to 33 months IC-ORR was the percentage of participant with intracranial objective response of complete response (CR) or partial response (PR) based on intracranial disease in the subset of participants with at least 1 intracranial lesion per RECIST version 1.1 (modified) recorded from randomization until disease progression or start of new anti-cancer therapy. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). PR was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Overall Survival (OS) From time of Study Start up to 33 months OS was defined as the time from randomization to the date of death due to any cause. OS (in months) was calculated as (date of death or censoring - start date +1)/30.4375. Participants last known to be alive were censored at date of last contact.
Objective Response Rate (ORR) - Percentage of Participants With Objective Response (OR) Based on BICR Assessment From time of Study Start up to 33 months ORR was the percentage of participants with objective response of complete response (CR) or partial response (PR) according to RECIST version 1.1 recorded from randomization until disease progression or start of new anti-cancer therapy. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). PR was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Intracranial Time to Progression (IC-TTP) Based on BICR Assessment From time of Study Start up to 33 months IC-TTP based on BICR assessment was defined as the time from date of randomization to the date of the first documentation of progression of intracranial disease, based on either new brain metastases or progression of existing brain metastases.
Duration of Response (DR) Based on BICR Assessment From time of Study Start up to 33 months DR was defined, for participants with a confirmed objective response (OR) of complete response (CR) or partial response (PR) per RECIST version 1.1, as the time from the first documentation of OR to the first documentation of progressive disease (PD) or death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). PR was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.
Intracranial Duration of Response (IC-DR) Based on BICR Assessment From time of Study Start up to 33 months IC-DR was defined, for participants with a confirmed intracranial objective response (OR) of complete response (CR) or partial response (PR) per RECIST version 1.1, as the time from the first documentation of intracranial OR to the first documentation of intracranial progressive disease (PD) or death due to any cause, whichever occurred first. CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). PR was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of 1 or more new lesions.
Time to Tumor Response (TTR) Based on BICR Assessment From time of Study Start up to 33 months TTR based on BICR assessment was defined, for participants with a confirmed objective response, as the time from the date of randomization to the first documentation of objective response (complete response or partial response) which was subsequently confirmed. Complete response was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). Partial response was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Intracranial Time to Tumor Response (IC-TTR) Based on BICR Assessment From time of Study Start up to 33 months IC-TTR was defined, for participants with a confirmed intracranial objective response, as the time from the date of randomization to the first documentation of intracranial objective response (complete response or partial response) which was subsequently confirmed. Complete response was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). Partial response was defined as at least a 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
PFS2 Based on Investigator's Assessment From time of Study Start up to 45 months PFS2 was defined as the time from randomization to the date of progression of disease on first subsequent systemic anti-cancer therapy, or death from any cause, whichever occurred first
Number of Participants With Treatment-Emergent Adverse Events (AEs; All-Causality and Treatment-Related) From time of Study Start up to 33 months An AE was an untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death, life-threatening experience, initial or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. All AEs in the table below were treatment-emergent AEs. Grade 3 and 4 AEs in the table below indicated severe AE and life-threatening consequences respectively; Grade 5 indicated death due to AE. Treatment-related AEs were determined by investigators.
Number of Participants With Changes in Hematology Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4 From Baseline up to 33 months Laboratory test results were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grades 1 and 2 indicate mild and moderate AE, respectively; Grades 3 and 4 indicate severe AE and life-threatening consequences respectively; Grade 5 indicates death due to AE. Participants with laboratory test abnormalities were summarized according to the worst grade for each laboratory test result. All participants meeting the postbaseline grade criteria in the table below had baseline maximum grades lower than 3.
Number of Participants With Changes in Chemistry Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4 From Baseline up to 33 months Laboratory test results were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grades 1 and 2 indicate mild and moderate AE, respectively; Grades 3 and 4 indicate severe AE and life-threatening consequences respectively; Grade 5 indicates death due to AE. Participants with laboratory test abnormalities were summarized according to the worst grade for each laboratory test result. All participants meeting the postbaseline grade criteria in the table below had baseline maximum grades lower than 3.
Number of Participants With Changes in Lipid Laboratory Parameters From Baseline Maximum NCI-CTCAE Grade Lower Than 3 to Postbaseline Maximum Grade 3 or Grade 4 From Baseline up to 33 months Laboratory test results were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grades 1 and 2 indicate mild and moderate AE, respectively; Grades 3 and 4 indicate severe AE and life-threatening consequences respectively; Grade 5 indicates death due to AE. Participants with laboratory test abnormalities were summarized according to the worst grade for each laboratory test result. All participants meeting the postbaseline grade criteria in the table below had baseline maximum grades lower than 3.
Number of Participant With Vital Signs and Body Weight Data Meeting Pre-defined Criteria From Baseline up to 33 months Vital signs data included pulse, systolic blood pressure, and diastolic blood pressure. Measurements were only provided once per timepoint. If multiple assessments were provided per timepoint, the maximum value were used for reporting. The pre-defined criteria of vital sign and body weight data were as follows: maximum pulse rate \>120 beats per minute (bpm); minimum pulse rate \<50 bpm; maximum increase in pulse rate ≥30 bpm; maximum decrease in pulse rate ≥30 bpm; increase in systolic blood Pressure ≥40 mmHg; decrease in systolic blood pressure ≥40 mmHg; decrease in systolic blood pressure ≥60 mmHg; increase in diastolic blood pressure ≥20 mmHg; decrease in diastolic blood pressure ≥20 mmHg; decrease in diastolic blood pressure ≥40 mmHg; increase in body weight ≥10%; increase in body weight ≥20%; decrease in body weight ≥10%.
Number of Participant With Maximum Increase From Baseline in Electrocardiogram (ECG) Data Meeting Pre-defined Criteria From Baseline up to 33 months Baseline was defined as the last assessment performed on or prior to date of the first dose of study treatment. Triplicate ECGs were collected in the study and the average of the replicate assessments were used for summary analysis. The pre-defined criteria of ECG data were as follows: change from baseline in QTcF ≥60 msec, ≥30 msec but \<60 msec, \<30 msec; change from baseline in QTcB ≥60 msec, ≥30 msec but \<60 msec, \<30 msec; PR change ≥50% if absolute baseline value was \<200 msec; PR change ≥25% if absolute baseline value was ≥200 msec; QRS change ≥50% if absolute baseline value was \<100 msec; QRS change ≥25% if absolute baseline value was ≥100 msec.
Number of Participants With Maximum Decrease From Baseline Greater Than or Equal to 20 Points in Left Ventricular Ejection Fraction (LVEF) Percentage From Baseline up to 33 months In this outcome measure, baseline was defined as the last assessment on or prior to the date of the first dose of study treatment. Decrease from baseline was an absolute difference between baseline and observed value.
Change From Baseline in Total Scores of Beck Depression Inventory (BDI)-II (Mood Assessment) Across Time Baseline, Cycle 2 Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C8D1, C10D1, C12D1, C14D1, C16D1, C18D1, C20D1, C22D1, C24D1, C26D1, C28D1, C30D1, C32D1, C34D1, C36D1, C38D1 and End of Treatment BDI-II (Mood Assessment) is a 21 item self-reported scale, with each item rated by participants on a 4-point scale (ranging from 0-3). The scale includes items capturing mood, (loss of pleasure, sadness, and irritability), suicidal ideation, and cognitive signs (punitive thoughts, self-criticism, self-dislike pessimism, poor concentration) as well as somatic signs (appetite, sleep, fatigue, libido). Scores were obtained by adding up the total points from the series of answers. The total score ranged from 0 to 63, with higher total scores indicating more severe depressive symptoms. The standardized cutoffs are as follows: 0-13: minimal depression; 14-19: mild depression; 20-28: moderate depression; 29-63: severe depression.
Number of Participants With Suicidal Ideation and Suicidal Behavior Across Time Baseline, Cycle 2 Day 1 (C2D1), C3D1, C4D1, C5D1, C6D1, C8D1, C10D1, C12D1, C14D1, C16D1, C18D1, C20D1, C22D1, C24D1, C26D1, C28D1, C30D1, C32D1, C34D1, C36D1, C38D1 and End of Treatment Suicidal ideation and behaviors were assessed by the Columbia Suicide Severity Rating Scale (C-SSRS). The C-SSRS is a unique, simple and short method of assessing both behavior and ideation that tracks all suicidal events and provides a summary of suicidality. It assesses the lethality of attempts and other features of ideation (frequency, duration, controllability, reasons for ideation, and deterrents), all of which are significantly predictive of completed suicide.
Change From Baseline in Lung Cancer Symptoms as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13) During Overall Treatment From Baseline up to Cycle 38 Day 1 The EORTC QLQ LC13 consists of 13 questions and includes 1 multi-item scale and 9 single items assessing symptoms (dyspnea, cough, haemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication use. The scale scores rang from 0 to 100, with higher scores indicating higher ("worse") level of symptoms.
Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Visual Analogue Scale (VAS) Across Time Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment The EuroQol EQ-5D-5L is a participant-completed questionnaire designed to assess health status. There are 2 components to the EuroQol EQ-5D-5L: a descriptive system in which individuals rate their level of problems (none, slight, moderate, severe, extreme/unable) in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a VAS. The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) and higher scores indicate better health state.
Time to Deterioration (TTD) in Participant Reported Pain in Chest, Dyspnea, or Cough From QLQ-LC13 From Baseline up to 33 months The EORTC QLQ LC13 consists of 13 questions and includes 1 multi-item scale and 9 single items assessing symptoms (dyspnea, cough, haemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication use. The scale scores rang from 0 to 100, with higher scores indicating higher ("worse") level of symptoms. TTD in pain in chest, dyspnea, or cough was defined as the time from randomization to the first time the participant's score showed a 10 point or greater increase after baseline in any of the 3 symptoms. TTD in months was calculated as (date of deterioration or censoring - randomization date +1)/30.4375.
Change From Baseline in Global Quality of Life (QOL), Functional Scales and Symptoms Scales as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) During Overall Treatment From Baseline up to Cycle 38 Day 1 The EORTC QLQ C30 consists of 30 questions and includes 5 functional scales (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale; 3 symptom scales (fatigue, pain, nausea and vomiting); and 6 single items that assess additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and financial impact. All scales and single item measures range in score from 0 to 100. Higher scores on the functional scales represent higher levels of functioning. Higher scores on the global health status/quality of life scale represent higher health status/quality of life. Higher scores on symptom scales/items represent a greater presence of symptoms.
Change From Baseline in Health Status as Assessed by EuroQol 5 Dimension 5 Level (EQ-5D-5L) - Index Across Time Baseline, Day 1 of all cycles from Cycle 2 to Cycle 38, and End of Treatment The EuroQol EQ-5D-5L is a participant-completed questionnaire designed to assess health status. There are 2 components to the EuroQol EQ-5D-5L: a descriptive system in which individuals rate their level of problems (none, slight, moderate, severe, extreme/unable) in 5 areas (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a VAS in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable). EQ-5D summary index is obtained with a formula that weights each level of the 5 dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health).
Number of Participant With ALK Domain Mutation in Plasma Circulating Nucleic Acid (CNA) Analysis at Screening, Cycle 2 Day 1 and Cycle 7 Day 1 at Screening, Cycle 2 Day 1 and Cycle 7 Day 1 The analysis of anaplastic lymphoma kinase (ALK) domain mutation in plasma CNA was performed by next-generation sequencing (NGS) and the number of participants with one or more ALK mutations at Screening, Cycle 2 Day 1 and Cycle 7 Day 1 is presented here.
Number of Participant With ALK Fusion Variant in Plasma Circulating Nucleic Acid (CNA) Analysis at Screening, Cycle 2 Day 1 and Cycle 7 Day 1 at Screening, Cycle 2 Day 1 and Cycle 7 Day 1 The analysis of ALK fusion variant in plasma CNA was performed by NGS and the number of participants with fusion variants at Screening, Cycle 2 Day 1 and Cycle 7 Day 1 is presented here. In the table below, EML4-ALK is the abbreviation of echinoderm microtubule-associated protein-like 4 anaplastic lymphoma kinase.
Trial Locations
- Locations (139)
The William P. Beetham Eye Institute, Joslin Diabetes Center
🇺🇸Boston, Massachusetts, United States
Ophthalmic Consultants of Boston Inc
🇺🇸Boston, Massachusetts, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas
🇲🇽Distrito Federal, Mexico
Raffles Hospital
🇸🇬Singapore, Singapore
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie-Panstwowy Instytut Badawczy
🇵🇱Warszawa, Poland
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Beijing Cancer Hospital
🇨🇳Beijing, China
Hopital de Chevilly Larue
🇫🇷Chevilly Larue, France
Melbourne Pathology
🇦🇺Bendigo, Victoria, Australia
The Affiliated Hospital of Military Medical Sciences
🇨🇳Beijing, Beijing, China
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
McGill University Health Centre
🇨🇦Montreal, Quebec, Canada
Guangdong General Hospital
🇨🇳Guangzhou, China
Fakultni nemocnice Olomouc, Klinika plicnich nemoci a tuberkulozy
🇨🇿Olomouc, Czechia
Hôpital Nord
🇫🇷Marseille cedex 20, France
Hopital Pierre Paul Riquet
🇫🇷Toulouse cedex 9, France
The University of Hong Kong, Department of Clinical Oncology
🇭🇰Hong Kong, Hong Kong
Vseobecna fakultni nemocnice v Praze
🇨🇿Praha 2, Czechia
Artemis Hospital
🇮🇳Gurugram, Haryana, India
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, MI, Italy
Azienda Ospedaliero-Universitaria di Parma
🇮🇹Parma, PR, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, RM, Italy
Istituto Nazionale Tumori di Napoli
🇮🇹Napoli, Italy
Universitätsklinikum des Saarlandes, Innere Medizin V
🇩🇪Homburg - Saar, Germany
Universitatsklinikum Regensburg, Institut fur Rontgendiagnostik
🇩🇪Regensburg, Germany
Sendai Kousei Hospital
🇯🇵Sendai, Miyagi, Japan
CHU de Rennes Hopital Pontchaillou
🇫🇷Rennes cedex 9, France
CHU de Rennes, Hopital Pontchaillou
🇫🇷Rennes cedex 9, France
Département d'Imagerie Médicale
🇫🇷Marseille cedex 20, France
AOU Policlinico Vittorio Emanuele-P.O.G. Rodolico
🇮🇹Catania, CT, Italy
Hopital Foch
🇫🇷Suresnes, France
Kindai University Hospital
🇯🇵Osakasayama, Osaka, Japan
Department d'imagerie medicale
🇫🇷Villejuif, France
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Complejo Hospitalario De Navarra
🇪🇸Pamplona, Navarra, Spain
Manipal Hospital
🇮🇳Bangalore, Karnataka, India
Centrum Medyczne Dom Lekarski S.A.
🇵🇱Szczecin, Poland
IRCCS Ospedale San Raffaele
🇮🇹Milano, MI, Italy
Shizuoka Cancer Center
🇯🇵Sunto-gun, Shizuoka, Japan
Kanagawa Cancer Center
🇯🇵Yokohama, Kanagawa, Japan
Hopital Larrey
🇫🇷Toulouse Cedex 9, France
Universitatsklinikum Regensburg, Klinik und Poliklinik fur Innere Medizin II
🇩🇪Regensburg, Germany
Kanazawa University Hospital
🇯🇵Kanazawa, Ishikawa, Japan
Sahyadri Clinical Research and Development Centre
🇮🇳Pune, Maharashtra, India
Hospital Universitario Puerta de Hierro Majadahonda
🇪🇸Majadahonda, Madrid, Spain
Ausl della Romagna- Ravenna
🇮🇹Ravenna, Italy
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Osaka International Cancer Institute
🇯🇵Osaka-shi, Osaka, Japan
LEC at SBIH "Saint-Petersburg Clinical Research Practical Center of specialized types of
🇷🇺Pesochniy Poselok, Saint-petersburg, Russian Federation
Aichi cancer center central hospital
🇯🇵Nagoya, Aichi, Japan
Tokushima University Hospital
🇯🇵Tokushima, Japan
Uberortliche Radiologische Gemeinschaftspraxis Dr. med. Marc Amler
🇩🇪Dresden, Germany
Med-Polonia Sp. z o.o.
🇵🇱Poznan, Poland
Chang Gung Memorial Hospital - Kaohsiung Branch
🇨🇳Kaohsiung, Taiwan
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsuyama, Ehime, Japan
FSBI "N.N.Blokhin Medical Research Center of Oncology"
🇷🇺Moscow, Russian Federation
ASST Monza - A.O. San Gerardo
🇮🇹Monza, MB, Italy
Institut Catala d'Oncologia Girona
🇪🇸Girona, Spain
Osaka City General Hospital
🇯🇵Osaka, Japan
Wakayama Medical University Department of Pulmonary Medicine and Oncology
🇯🇵Wakayama, Japan
National Cancer Center Hospital
🇯🇵Chuo-Ku, Tokyo, Japan
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Médicos Especialistas en Cancer S.C. / San Peregrino.
🇲🇽Aguascalientes, Mexico
Instituto Nacional de Cancerologia
🇲🇽Distrito Federal, Mexico
National University Hospital
🇸🇬Singapore, Singapore
National Taiwan University Hospital
🇨🇳Taipei, Taiwan ROC, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Cukurova University Medical Faculty
🇹🇷Adana, Turkey
Istanbul University Oncology Institute
🇹🇷Istanbul, Turkey
Hospital Teresa Herrera C.H.U.A.C.
🇪🇸A Coruna, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Marmara Univ Pendik Training and Research Hospital
🇹🇷Istanbul, Turkey
The Ipswich Hospital NHS Trust
🇬🇧Ipswich, Suffolk, United Kingdom
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Istituto Europeo di Oncologia
🇮🇹Milano, MI, Italy
Azienda Ospedaliera di Perugia - Ospedale S. M. Misericordia
🇮🇹Perugia, PG, Italy
Az.Osp.San Camillo-Forlanini
🇮🇹Roma, RM, Italy
Azienda Ospedaliera Dei Colli Ospedale Monaldi
🇮🇹Napoli, Italy
Hôpital Larrey
🇫🇷Toulouse Cedex 9, France
The Cancer Institute Hospital of JFCR
🇯🇵Koto-ku, Tokyo, Japan
Service Ophtalmologie
🇫🇷Marseille cedex 20, France
Florida Cancer Specialists
🇺🇸Winter Park, Florida, United States
University of Rochester Cancer Center Pharmacy
🇺🇸Rochester, New York, United States
Tennessee Oncology, PLLC
🇺🇸Smyrna, Tennessee, United States
The Sarah Cannon Research Institute.
🇺🇸Nashville, Tennessee, United States
Centro Medico Austral
🇦🇷Caba, Argentina
Centro de Investigacion Pergamino SA
🇦🇷Pergamino, Buenos Aires, Argentina
Bendigo Day Surgery Collection Centre and Laboratory
🇦🇺Bendigo, Victoria, Australia
Bendigo Medical Imaging, Bendigo Hospital
🇦🇺Bendigo, Victoria, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Grand Hopital de Charleroi - Site Notre Dame
🇧🇪Charleroi, Belgium
Shanghai Chest Hospital
🇨🇳Shanghai, Shanghai, China
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Jilin Provincial Cancer Hospital
🇨🇳Changchun, Jilin, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, Zhejiang, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Hopital Haut-Léveque-Centre François Magendie
🇫🇷Pessac, Aquitaine, France
Department of Respiratory,the First Affiliated Hospital of College of Medicine, Zhejiang University
🇨🇳Hangzhou, Zhejiang, China
Centre Hospitalier du Mans
🇫🇷Le Mans, France
Institut Paoli-Calmettes
🇫🇷Marseille cedex 09, France
Technische Universitat Dresden , Medizinische Fakultat Carl Gustav Carus
🇩🇪Dresden, Germany
Groupe Hospitalier Bichat Claude Bernard, AP-HP
🇫🇷Paris, France
Universitatsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Institut Gustave Roussy
🇫🇷Villejuif, France
Universitätsklinikum des Saarlandes
🇩🇪Homburg - Saar, Germany
Thoraxklinik Heidelberg gGmbH
🇩🇪Heidelberg, Germany
Tuen Mun Hospital
🇭🇰Hong Kong, Hong Kong
Istituto Clinico Humanitas
🇮🇹Rozzano, MI, Italy
Centro di Riferimento Oncologico-IRCCS
🇮🇹Pordenone, PN, Italy
Nagoya University Hospital
🇯🇵Nagoya, Aichi, Japan
Kurume University Hospital
🇯🇵Kurume, Fukuoka, Japan
National Hospital Organization Hokkaido Cancer Center
🇯🇵Sapporo, Hokkaido, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
National Hospital Organization, Yamaguchi-Ube Medical Center
🇯🇵Ube, Yamaguchi, Japan
Division of Medical Oncology, Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, St. Vincents Hospital
🇰🇷Suwon, Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
RBHI Kursk Regional Clinical Oncology Dispensary
🇷🇺Kursk, Russian Federation
Budgetary Healthcare Institution Omsk Region "Clinical Oncological Dispensary"
🇷🇺Omsk, OMSK Region, Russian Federation
Private Medical Institution "Euromedservice"
🇷🇺Pushkin, Saint-petersburg, Russian Federation
Institut Catala d'Oncologia L'Hospitalet
🇪🇸L'Hospitalet de Llobregat, Barcelona, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
Hospital De La Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Chung Shan Medical University Hospital
🇨🇳Taichung, Taiwan
Hospital Universitario La Fe
🇪🇸Valencia, Spain
Ege University Medical Faculty
🇹🇷Izmir, Turkey
Heart of England NHS Foundation Trust, Birmingham Heartlands Hospital
🇬🇧Birmingham, WEST Midlands, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Klinika Onkologii i Radioterapii Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Massachusetts Eye and Ear Infirmary
🇺🇸Boston, Massachusetts, United States
Srinivasam Cancer Care Multispeciality Hospitals India Pvt Ltd
🇮🇳Bangalore, Karnataka, India
Sahyadri Specialty Hospital
🇮🇳Pune, Maharashtra, India
Hospital Universitario Insular de Gran Canaria
🇪🇸Las Palmas de Gran Canaria, Canarias, Spain
The University of Hong Kong, Department of Medicine
🇭🇰Hong Kong, Hong Kong