A Clinical Trial Testing The Efficacy Of Crizotinib Versus Standard Chemotherapy Pemetrexed Plus Cisplatin Or Carboplatin In Patients With ALK Positive Non Squamous Cancer Of The Lung

Phase 3

Completed

Conditions: Non Squamous Lung Cancer

Interventions: Drug: treatment

Registration Number: NCT01154140

Lead Sponsor: Pfizer

Brief Summary: This study will evaluate the anti-cancer effects of crizotinib when compared with standard chemotherapy in patients with ALK positive lung cancer.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 343

Inclusion Criteria

Proven diagnosis of locally advanced not suitable for local treatment, recurrent and metastatic non-squamous cell carcinoma of the lung
Positive for translocation or inversion events involving the ALK gene locus
No prior systemic treatment for locally advanced or metastatic disease; Patients with brain metastases only if treated and neurologically stable with no ongoing requirement for corticosteroids
Evidence of a personally signed and dated informed consent document and willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures including completion of patient reported outcome [PRO] measures.
18 years of age or older with the exception of India which has an upper age limit of 65 years old

Exclusion Criteria

Current treatment on another therapeutic clinical trial.
Prior therapy directly targeting ALK.
Any of the following within the 3 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, congestive heart failure, or cerebrovascular accident including transient ischemic attack. - - Appropriate treatment with anticoagulants is permitted.
Ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, uncontrolled atrial fibrillation of any grade, or QTc interval >470 msec.
Pregnancy or breastfeeding.
Use of drugs or foods that are known potent CYP3A4 inducers/inhibitors Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices.
Known HIV infection
Known interstitial lung disease or interstitial fibrosis
Other severe acute or chronic medical conditions (including severe gastrointestinal conditions such as diarrhea or ulcer) or psychiatric conditions, or laboratory abnormalities that would impart, in the judgment of the investigator and/or sponsor, excess risk associated with study participation or study drug administration, and which would, therefore, make the patient inappropriate for entry into this study

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	treatment	-
B	treatment	-

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) Based on IRR	Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)	PFS was defined as the time from the date of randomization in study until the date of first documented objective tumor progression (according to RECIST v1.1 as determined by IRR) or death (due to any cause), whichever occurred first. PFS (in months) was calculated as (first event date - randomization date +1)/30.44. Objective progression was defined as a 20 percent (%) increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 millimeter (mm) or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	From randomization to death or last date known alive for those not known to have died (up to 72 months)	OS (in months) was defined as the duration from start of study treatment to date of death due to any cause. OS = (date of death minus the date of randomization of study medication plus 1) divided by 30.4. For participants who were alive, overall survival was censored on last date the participants were known to be alive.
Overall Survival Probability at Month 12 and 18	Month 12, 18	Overall survival probability at Month 12 and 18 was defined as the probability of overall survival at 12 and 18 months respectively, where the OS was defined as the duration from date of randomization to date of death due to any cause. The survival probability was estimated using the Kaplan-Meier method.
Objective Response Rate (ORR): Percentage of Participants With Objective Response as Assessed by IRR	Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)	ORR was defined as percentage of participants with complete response (CR) or partial response (PR) according to RECIST v1.1 determined by IRR. 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). No new lesions and disappearance of all non-target lesions. PR was defined as greater than or equal to (\>=) 30% decrease taking as reference the baseline sum of lesion dimensions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No clear progression of non-target disease. No new lesions.
Duration of Response (DR) Based on IRR	From objective response to date of progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)	DR: time from first documentation of objective tumor response (CR or PR) to first documentation of PD or death due to any cause, whichever occurred first as per RECIST v1.1 determined by IRR. CR: complete disappearance of all target and non-target disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions, disappearance of all non-target lesions. PR: \>=30% decrease taking as reference the baseline sum of lesion dimensions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions. c) PD: 20 % increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.
Time to Tumor Response (TTR) Based on IRR	Randomization to first documentation of objective tumor response (up to 35 months)	TTR was defined as the time from randomization to first documentation of objective tumor response (CR or PR) according to RECIST v1.1 determined by IRR. CR: 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). No new lesions and disappearance of all non-target lesions. PR: \>=30% decrease taking as reference the baseline sum of lesion dimensions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions.
Percentage of Participants With Disease Control at Week 12 Based on IRR	Week 12	Disease control rate at week 12 is defined as the percent of participants with CR, PR, or stable disease (SD) at week 12 according to RECIST v1.1 determined by IRR. The best response of SD would be assigned if SD criteria was met at least once after randomization at a minimum interval of 6 weeks. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions and disappearance of all non-target lesions. PR: \>=30% decrease taking as reference the baseline sum of lesion dimensions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions.
Time to Progression (TTP) Based on IRR	Randomization to objective progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)	TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions. If tumor progression data included more than 1 date, the first date was used. TTP (in months) was calculated as (first event date - randomization date +1)/30.44.
Time to Intracranial Progression (IC-TTP) Based on IRR	Randomization to objective intracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)	IC-TTP was defined similarly to TTP, but only considering intracranial disease (excluding extracranial disease) and the progression was determined based on either new brain metastases or progression of existing brain metastases. TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.
Time to Extracranial Progression (EC-TTP) Based on IRR	Randomization to objective extracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)	EC-TTP was defined similarly to TTP, but only considering extracranial disease (excluding intracranial disease) and the progression was determined based on either new extracranial lesions or progression of existing extracranial lesions. TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression according to RECIST v1.1 determined by IRR. Objective tumor progression was defined as 20% increase in the sum of the diameters of target measurable lesions taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study), with a minimum absolute increase of 5 mm or clear progression of pre-existing non-target lesions, or the appearance of any new clear lesions.
Percentage of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to follow up period (up to 72 months)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug that were absent before treatment or that worsened relative to pretreatment state. AEs included both SAEs and non-SAEs.
Percentage of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)	Baseline up to follow up period (up to 72 months)	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose of study drug that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.
Percentage of Participants With Adverse Events (AEs) According to Maximum Severity	Baseline up to follow up period (up to 72 months)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to maximum severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Grade 1 =mild; Grade 2 =moderate; within normal limits, Grade 3 =severe or medically significant but not immediately life-threatening; Grade 4 =life-threatening or disabling; urgent intervention indicated; Grade 5 =death.
Plasma Predose Concentration (Ctrough) of Crizotinib and Its Metabolite PF-06260182	Predose at Day 1 of Cycle 2, 3 and 5	Ctrough is the concentration prior to study drug administration on Day 1 of Cycle 2 onwards. PF-06260182 is the metabolite of Crizotinib.
Percentage of Participants For Each Anaplastic Lymphoma Kinase (ALK) Gene Fusion Variants	28 days prior to day 1 of study treatment	The Response Genetics, Inc. Echinoderm Microtubule Associated Protein Like 4 (EML4) ALK reverse transcriptase polymerase chain reaction (RT PCR) gene fusion test was used for the analysis of tissue samples for the ALK gene fusion variants (either no rearrangement, or 1 of 9 results reflecting 8 specific rearrangements \[V1, V2, V3a, V3b,V3a/b, V4, V5a, V6, V7\]). Percentage of participants who tested positive for ALK gene fusion variants were reported in this outcome measure.
Objective Response Rate (ORR) of Anaplastic Lymphoma Kinase (ALK) Variant Groups Based on IRR	Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (up to 35 months)	The Response Genetics, Inc. EML4 ALK reverse transcriptase polymerase chain reaction (RT PCR) gene fusion test was used for the analysis of tissue samples for the ALK gene fusion variants (either no rearrangement, or 1 of 9 results reflecting 8 specific rearrangements \[V1, V2, V3a, V3b,V3a/b, V4, V5a, V6, V7\]). Percentage of participants with confirmed CR or PR according to RECIST v1.1 determined by IRR, by type of ALK gene fusion variant were reported in this outcome measure. CR: 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). No new lesions and disappearance of all non-target lesions. PR: \>=30% decrease decrease taking as reference the baseline sum of lesion dimensions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all or target lesions. No clear progression of non-target disease. No new lesions.
Time to Deterioration (TTD) in Chest Pain, Dyspnea or Cough	From randomization of treatment up to deterioration while on study treatment (up to 35 months)	TTD in pain in chest, dyspnea, or cough from the Quality of Life Questionnaire Core 30 (QLQ-LC13) was a composite endpoint defined as the time from randomization to the earliest time the participant's scale scores showed a 10 point or greater increase after baseline in any of the 3 symptoms. For those who had not shown deterioration, the data was censored at the last date when the participants completed an assessment (QLQ-LC13) for pain, dyspnea, or cough or at last visit date prior to crossover for participants randomized to chemotherapy who subsequently crossed over to crizotinib. A 10-point or higher change in the score was perceived by participants as clinically significant. The transformed score of pain, dyspnea, and cough symptom scales of EORTC QLQ-LC13 (European Organization for the Research and Treatment of Cancer) range from 0 to 100, where higher scores indicate greater symptom severity.
Change From Baseline in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)	Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)	EORTC QLQ-C30: included 5 functional scales (physical, role, cognitive, emotional and social), global health status/global quality of life scale, 3 symptom scales (fatigue, pain, nausea and vomiting), 6 single items that assess the additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea) and financial difficulties. All scales and single-item measures range from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning, for the global health status/QoL represents a high QoL (better participant state), and for a symptom scale/item represents a high level of symptoms/problems (worse participant state).
Change From Baseline Scores in QLQ-C30 Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)	Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)	EORTC QLQ-C30: included 5 functional scales (physical, role, cognitive, emotional and social), global health status/global quality of life scale, 3 symptom scales (fatigue, pain, nausea and vomiting), 6 single items that assess the additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea) and financial difficulties. All scales and single-item measures range from 0 to 100. A high score for a functional scale represents a high/healthy level of functioning, for the global health status/QoL represents a high QoL (better participant state), and for a symptom scale/item represents a high level of symptoms/problems (worse participant state).
Change From Baseline in Lung Cancer Symptom Scores as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 13 (QLQ- LC13)	Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)	QLQ-LC13 consists of 1 multi-item scale and 9 single items that assess the specific symptoms (dyspnea, cough, hemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use of patients with lung cancer receiving chemotherapy. All multi-item scales and single-item measures range from 0 to 100, where higher score indicates greater degree of symptom severity.
Change From Baseline in General Health Status as Assessed by EuroQol 5D (EQ-5D)- Visual Analog Scale (VAS)	Baseline, From Cycle 1 Day 1 up to end of study treatment or crossover to crizotinib arm (up to 35 months)	EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. VAS component: participants rated their current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health.
Percentage of Participants With Hospital Admissions-Healthcare Resource Utilization (HCRU)	Baseline up to follow up period (up to 72 months)	Healthcare resource utilization was to be evaluated using the assessment of the following: date and duration of index admission, duration of hospitalization and date of discharge.
Percentage of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities	Baseline up to follow up period (up to 72 months)	Anemia(grade\[g\]1:Less than\[\<\] Lower limit of normal\[LLN\] to 10gram per\[/\] deciliter\[g/dL\],g2:\<10 to 8g/dL,g3:\<8g/dL,g4:lifethreatening);platelet (g1:\<LLN to 75\10\^3/millimeter\[mm\]\^3,g2:\<75\10\^3/mm\^3 to 50\10\^3/mm\^3,g3:\<50\10\^3/mm\^3 to 25\10\^3/mm\^3,g4:\<25\10\^3/mm\^3);lymphopenia(g1:\<LLN to 8\10\^2/mm\^3,g2:\<8\10\^2 to 5\10\^2/mm\^3,g3:\<5\10\^2 to 2\10\^2/mm\^3,g4:\<2\10\^2/mm\^3);neutrophil (Absolute)(g1:\<LLN to 15\10\^2/mm\^3,g2:\<15\10\^2 to 10\10\^2/mm\^3,g3:\<10\10\^2 to 5\10\^2/mm\^3,g4:\<5\10\^2/mm\^3);white blood cell count(g1:\<LLN to 3\10\^3/mm\^3,g2:\<3\10\^3 to 2\10\^3/mm\^3,g3:\<2\10\^3 to 1\10\^3/mm\^3,g4:\<1\10\^3/mm\^3);hemoglobin(g1:increase in hemoglobin level\>0 to 2 g/dL above ULN or above baseline if baseline is above ULN,g2:increase in hemoglobin level\>2 to 4g/dL above ULN or above baseline if baseline is above ULN,g3:increase in hemoglobin level\>4 g/dL above ULN or above baseline if baseline is above ULN). Only categories with atleast 1 participant with abnormality are reported in this outcome measure.
Percentage of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities	Baseline up to follow up period (up to 72 months)	ALT/AST (Grade\[g\]1:\>ULN-3\ULN,g2:\>3-5\ULN,g3:\>5-20\ULN,g4:\>20\ULN);Alkaline Phosphatase (g1:\>ULN-2.5\ULN,g2:\>2.5-5\ULN,g3:\>5-20\ULN,g4:\>20\ULN);Creatinine (g1:\>ULN-1.5\ULN,g2:\>1.5-3\ULN,g3:\>3-6\ULN,g4:\>6\ULN);hyperglycemia (g1:\>ULN-160,g2:\>160-250,g3:\>250-500,g4:\>500mg/dL);bilirubin(total) (g1:\>ULN-1.5\ULN,g2:\>1.5-3\ULN,g3:\>3-10\ULN,g4:\>10\ULN);hypoglycaemia (g1:\<LLN-55,g2:\<55-40,g3:\<40-30,g4:\<30mg/dL);hyperkalemia (g1:\>ULN-5.5,g2:\>5.5-6,g3:\>6-7,g4:\>7mmol/L);hypokalemia (g1:\<LLN-3,g2:\<LLN-3,g3:\<3-2.5,g4:\<2.5mmol/L);hypermagnesemia (g1:\>ULN-3,g3:\>3-8,g4:\>8mg/dL);hypocalcemia (g1:\<LLN-8,g2:\<8-7,g3:\<7-6,g4:\<6mg/dL); hypercalcemia (g1:\>ULN-11.5,g2:\>11.5-12.5,g3:\>12.5-13.5,g4:\>13.5mg/dL);hypomagnesemia (g1:\<LLN-1.2,g2:\<1.2-0.9,g3:\<0.9-0.7,g4:\<0.7mg/dL);hyponatremia (g1:\<LLN-130,g3:\<130-120,g4:\<120mmol/L);hypoalbuminemia (g1:\<LLN-3,g2:\<3-2,g3:\<2,g4:lifethreatening);hypophosphatemia (g1:\<LLN-2.5,g2:\<2.5-2,g3:\<2-1,g4:\<1mg/dL). Participant\>=1 abnormality given.

Trial Locations

Locations (219): Tata Memorial Centre, Tata Memorial Hospital,
🇮🇳
Mumbai, Maharashtra, India
Struttura Operativa Complessa Oncologia Medica A Centro di Riferimento Oncologico
🇮🇹
Aviano, Pordenone, Italy
The Cancer Institute Hospital of JFCR
🇯🇵
Koto-ku, Tokyo, Japan
Russian Oncological Research Center N.N. Blokhin
🇷🇺
Moscow, Russian Federation
Russian Scientific Center of Radiology and Surgical Technologies
🇷🇺
Saint-Petersburg, Russian Federation
Instituto Nacional del Cancer
🇨🇱
Santiago, RM, Chile
Hospital Clinico Universidad de Chile, Seccion de Oncologia
🇨🇱
Independencia, Santiago, Rm, Chile
Helsingin yliopistollinen keskussairaala, Meilahden kolmiosairaala,Keuhkosairauksien poliklinikka
🇫🇮
Helsinki, Finland
Satakunnan keskussairaala/Keuhkosairauksien osasto A4
🇫🇮
Pori, Finland
Queen Elizabeth II Hospital
🇬🇧
Welwyn Garden City, Hertfordshire, United Kingdom
Spire Manchester Hospital
🇬🇧
Manchester, Lancashire, United Kingdom
Shanghai Chest Hospital/Department of Pulmonary Medicine
🇨🇳
Shanghai, China
Associacao Hospital de Caridade de Ijui
🇧🇷
Ijui, RS, Brazil
Instituto Nacional de Cancer - INCA
🇧🇷
Rio de Janeiro, RJ, Brazil
Centre Hospitalier Universitaire de Liege
🇧🇪
Liege, Belgium
Shanghai Pulmonary Hospital/Dept. of Oncology
🇨🇳
Shanghai, China
Istituto dei tumori Giovanni Paolo II
🇮🇹
Bari, Italy
QEII Health Sciences Centre
🇨🇦
Halifax, Nova Scotia, Canada
Hospital Sao Lucas da PUCRS
🇧🇷
Porto Alegre, RS, Brazil
Instituto Clinico Oncologico del Sur
🇨🇱
Temuco, Cautin, Chile
Hopital Avicenne
🇫🇷
Bobigny Cedex, France
Hopital Arnaud de Villeneuve / CHU de Montpellier
🇫🇷
Montpellier, France
HSK Dr.- Horst-Schmidt-Kliniken GmbH,
🇩🇪
Wiesbaden, Germany
Institut Jules Bordet, Centre des Tumeurs de l'ULB
🇧🇪
Bruxelles, Belgium
CHU de Caen
🇫🇷
Caen Cedex, France
Centre Leon Berard
🇫🇷
Lyon Cedex 08, France
Zentralklinik Bad Berka GmbH
🇩🇪
Bad Berka, Germany
Kliniken Maria Hilf GmbH
🇩🇪
Moenchengladbach, Germany
Thoraxklinik am Universitaetsklinikum Heidelberg
🇩🇪
Heidelberg, Germany
Oncology Center, Guangdong General Hospital
🇨🇳
Guangzhou, Guangdong, China
Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira - ICESP
🇧🇷
Sao Paulo, SP, Brazil
Universitair Ziekenhuis Gent (U.Z. Gent)
🇧🇪
Gent, Belgium
Department of Pulmonary Diseases AZ Delta
🇧🇪
Roeselare, Belgium
Zhongshan Hospital Fudan University
🇨🇳
Shanghai, China
Cross Cancer Institute
🇨🇦
Edmonton, Alberta, Canada
McGill University Health Centre (MUHC), Glen Site, Cedars Cancer Centre
🇨🇦
Montreal, Quebec, Canada
No.81 Hospital of the PLA
🇨🇳
Nanjing, Jiangsu, China
Charite - Universitaetsmedizin Berlin, Campus Mitte
🇩🇪
Berlin, Germany
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
🇨🇳
Beijing, China
Oncology Department, West China Hospital of Sichuan University
🇨🇳
Chengdu, Sichuan, China
CHU Grenoble
🇫🇷
Grenoble Cedex, France
Unità Operativa di Oncologia Medica Azienda USL Città di Bologna
🇮🇹
Bologna, Italy
Fondazione IRCCS Istituto Nazionale Tumori, Struttura Complessa di Medicina Oncologica 1
🇮🇹
Milano, Italy
Istituto Regina Elena, Struttura Complessa Oncologia Medica A
🇮🇹
Roma, Italy
Seoul National University Hospital
🇰🇷
Seoul, Korea, Republic of
Centro Hospitalar de Vila Nova de Gaia/Espinho, E.P.E.
🇵🇹
Vila Nova de Gaia, Portugal
Universitaetsspital Basel
🇨🇭
Basel, Switzerland
Oncologia Medica, Azienda Ospedaliero- Universitaria di Parma
🇮🇹
Parma, Italy
Hopital Tenon, Service de Pneumologie
🇫🇷
Paris cedex 20, France
Nouvel Hopital Civil - HSU - Pôle de Pathologie Thoracique - Service de Pneumologie
🇫🇷
Strasbourg, France
Institut universitaire de cardiologie et de pneumologie de Quebec (IUCPQ)
🇨🇦
Ste-Foy, Quebec, Canada
Loma Linda University Cancer Center
🇺🇸
Loma Linda, California, United States
Loma Linda University Cancer Center (LLUCC)-Schuman Pavilion
🇺🇸
Loma Linda, California, United States
Loma Linda University Medical Center
🇺🇸
Loma Linda, California, United States
Kaiser Permanente Southern California
🇺🇸
San Diego, California, United States
Indiana University Melvin and Bren Simon Cancer Center
🇺🇸
Indianapolis, Indiana, United States
Lois and Eskenazi Hospital
🇺🇸
Indianapolis, Indiana, United States
Kresge Eye Institute
🇺🇸
Detroit, Michigan, United States
Karmanos Cancer Institute
🇺🇸
Detroit, Michigan, United States
Karmanos Cancer Institute at Farmington Hills
🇺🇸
Farmington Hills, Michigan, United States
SUNY Upstate Medical University
🇺🇸
Syracuse, New York, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
UT Southwestern Medical Center - Simmons Cancer Center Pharmacy
🇺🇸
Dallas, Texas, United States
UT Southwestern University Hospital - William P. Clements, Jr.
🇺🇸
Dallas, Texas, United States
Chris O'Brien Lifehouse
🇦🇺
Camperdown, New South Wales, Australia
Sarah Cannon Research Institute
🇺🇸
Nashville, Tennessee, United States
Henry-Joyce Cancer Clinic
🇺🇸
Nashville, Tennessee, United States
Vanderbilt Oncology Pharmacy
🇺🇸
Nashville, Tennessee, United States
UT Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
University of Texas MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
University of Washington Medical Center
🇺🇸
Seattle, Washington, United States
The Royal Brisbane & Womens Hospital
🇦🇺
Herston, Queensland, Australia
Fundacao Pio XII Hospital de Cancer de Barretos
🇧🇷
Barretos, São Paulo, Brazil
R.S. McLaughlin Durham Regional Cancer Centre
🇨🇦
Oshawa, Ontario, Canada
Tower Cancer Research Foundation
🇺🇸
Beverly Hills, California, United States
CCTAP
🇺🇸
San Diego, California, United States
Florida Hospital
🇺🇸
Orlando, Florida, United States
Lynn Cancer Institute Center for Hematology Oncology
🇺🇸
Boca Raton, Florida, United States
Cancer Institute of Florida
🇺🇸
Orlando, Florida, United States
Georgetown University Hospital
🇺🇸
Washington, D.C., District of Columbia, United States
Research Pharmacy, Georgetown University Medical Center
🇺🇸
Washington, D.C., District of Columbia, United States
Investigational Drug Services
🇺🇸
Orlando, Florida, United States
Georgia Cancer Specialists
🇺🇸
Sandy Springs, Georgia, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
Al Fisher, Pharm D.
🇺🇸
Harvey, Illinois, United States
Indiana University Hospital
🇺🇸
Indianapolis, Indiana, United States
Ingalls Memorial Hospital
🇺🇸
Harvey, Illinois, United States
Monroe Medical Associates
🇺🇸
Tinley Park, Illinois, United States
Monroe Medical Association
🇺🇸
Munster, Indiana, United States
The Community Hospital
🇺🇸
Munster, Indiana, United States
Siteman Cancer Center - West County
🇺🇸
Creve Coeur, Missouri, United States
Barnes-Jewish Hospital
🇺🇸
Saint Louis, Missouri, United States
Washington University Center for Advanced Medicine Infusion Center Pharmacy
🇺🇸
Saint Louis, Missouri, United States
Siteman Cancer Center
🇺🇸
Saint Peters, Missouri, United States
Dartmouth Hitchcock Medical Center
🇺🇸
Lebanon, New Hampshire, United States
North Shore University Hospital
🇺🇸
Manhasset, New York, United States
NSLIJ Health System/Monter Cancer Center
🇺🇸
Lake Success, New York, United States
Tennessee Oncology, PLLC
🇺🇸
Smyrna, Tennessee, United States
Pharma Resource
🇺🇸
East Providence, Rhode Island, United States
Vincent Armenio
🇺🇸
East Providence, Rhode Island, United States
Seattle Cancer Care Alliance
🇺🇸
Seattle, Washington, United States
University of Wisconsin Hospital and Clinics
🇺🇸
Madison, Wisconsin, United States
Macarthur Cancer Therapy Centre
🇦🇺
Campbelltown, New South Wales, Australia
Royal North Shore Hospital
🇦🇺
St. Leonards, New South Wales, Australia
The Prince Charles Hospital
🇦🇺
Chermside, Queensland, Australia
Parkhaven Medical Center
🇦🇺
Hyde Park, Queensland, Australia
Department of Medical Oncology
🇮🇪
Dublin, Ireland
Peter MacCallum Cancer Centre, Department of Haematology and Medical Oncology
🇦🇺
East Melbourne, Victoria, Australia
Peninsula & South Eastern Haematology and Oncology Group
🇦🇺
Frankston, Victoria, Australia
Klinikum Wels-Grieskirchen
🇦🇹
Wels, Austria
Grand Hopital de Charleroi -Site Notre Dame
🇧🇪
Charleroi, Hainaut, Belgium
UZ Antwerpen-Pneumologie
🇧🇪
Edegem, Antwerp, Belgium
Cliniques Universitaires St Luc
🇧🇪
Brussels, Belgium
Universitair Ziekenhuis Brussel / Medische Oncologie
🇧🇪
Brussel, Belgium
Jewish General Hospital
🇨🇦
Montreal, Quebec, Canada
307 Hospital of PLA
🇨🇳
Beijing, Beijing, China
Union Hospital, Tongji Medical College of Huazhong University of Science & Technology/Cancer Center
🇨🇳
Wuhan, Hubei, China
Tampereen yliopistollinen sairaala
🇫🇮
Tampere, Finland
Centre Oscar Lambret
🇫🇷
Lille, France
APHM - Hopital Nord / Service d'Oncologie Multidisciplinaire et Innovations Thérapeutiques
🇫🇷
Marseille Cedex 20, France
St.Vincentius-Kliniken Karlsruhe
🇩🇪
Karlsruhe, Germany
Prince of Wales Hospital
🇭🇰
Shatin, New Territories, Hong Kong
Pius-Hospital Oldenburg
🇩🇪
Oldenburg, Germany
Department of Clinical Oncology, Queen Elizabeth Hospital
🇭🇰
Kowloon, Hong Kong
Aseptic Compounding Unit
🇮🇪
Dublin, Ireland
The Gujarat Cancer & Research Institute (M.P Shah Cancer Hospital),
🇮🇳
Ahmedabad,, Gujarat, India
Farmacia
🇮🇹
Napoli, Italy
Azienda Ospedaliero-Universitaria "Mater Domini"
🇮🇹
Catanzaro, Italy
Unità Operativa di Farmacia - Campus Salvatore venuta
🇮🇹
Catanzaro, Italy
Ospedale Civile Azienda USL Toscana Nord Ovest
🇮🇹
Livorno, Italy
Unità Operativa Farmacia Ospedaliera PO di Livorno
🇮🇹
Livorno, Italy
Farmacia Istituto Europeo di Oncologia IRCCS, U.O. Farmacia
🇮🇹
Milano, Italy
Istituto Europeo di Oncologia
🇮🇹
Milano, Italy
Ospedale Niguarda Ca'Granda, Divisione Oncologia Medica Falck
🇮🇹
Milano, Italy
Azienda Ospedaliera Universitaria San Luigi Gonzaga
🇮🇹
Orbassano (TO), Italy
A.O.R.N. Ospedale Dei Colli - Monaldi
🇮🇹
Napoli, Italy
S.C. Farmacia Ospedaliera , Azienda Ospedaliero Universitaria San Luigi Gonzaga
🇮🇹
Orbassano (TO), Italy
Farmacia Ospedaliera
🇮🇹
Perugia, Italy
SC Oncologia Medica, Ospedale Santa Maria della Misericordia
🇮🇹
Perugia, Italy
IRCCS -Arcispedale S. Maria Nuova Tecnologie Avanzate e Modelli Assistenziali in Oncologia
🇮🇹
Reggio Emilia, Italy
Azienda Ospedaliera San Camillo Forlanini-Padiglione Flaiani
🇮🇹
Roma, Italy
Farmacia Interna
🇮🇹
Roma, Italy
National Cancer Center Hospital East
🇯🇵
Kashiwa, Chiba, Japan
National Hospital Organization Hokkaido Cancer Center
🇯🇵
Sapporo, Hokkaido, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵
Matsuyama, Ehime, Japan
Unita Operativa, Oncologia Medica, Istituto di Medicina Interna e Geriatria
🇮🇹
Roma, Italy
Hyogo Cancer Center
🇯🇵
Akashi, Hyogo, Japan
Okayama University Hospital
🇯🇵
Okayama-city, Okayama, Japan
Kinki University Hospital
🇯🇵
Osakasayama-shi, Osaka, Japan
Shizuoka Cancer Center
🇯🇵
Sunto-gun, Shizuoka, Japan
National Cancer Center Hospital
🇯🇵
Chuo-Ku, Tokyo, Japan
National Hospital Organization Yamaguchi-Ube Medical Center
🇯🇵
Ube-shi, Yamaguchi, Japan
National Hospital organization Kyushu Cancer Center
🇯🇵
Fukuoka, Japan
Kyushu University Hospital Respiratory Medicine
🇯🇵
Fukuoka, Japan
Centre Hospitalier de Luxembourg
🇱🇺
Luxembourg, Luxembourg
Samsung Medical Center, Sungkyunkwan Univ. School of Medicine
🇰🇷
Seoul, Korea, Republic of
Instituto Nacional de Cancerologia
🇲🇽
Mexico, D.f., Mexico
Jeroen Bosch Ziekenhuis
🇳🇱
's Hertogenbosch, NB, Netherlands
VUMC
🇳🇱
Amsterdam, Netherlands
Academisch Ziekenhuis Maastricht / afdeling longziekten en tuberculose
🇳🇱
Maastricht, Netherlands
Oslo universitetssykehus HF - Radiumhospitalet
🇳🇴
Oslo, Norway
Clinica Anglo Americana/Centro de Investigacion Oncologia CAA
🇵🇪
San Isidro, Lima, Peru
Instituto Português de Oncologia de Lisboa, Prof. Francisco Gentil E.P.E.
🇵🇹
Lisboa, Portugal
Centro Hospitalar e Universitario de Coimbra - Hospital Geral
🇵🇹
Coimbra, Portugal
Centro Hospitalar de Lisboa Norte - Hospital Pulido Valente
🇵🇹
Lisboa, Portugal
City Clinical Oncology Dispensary
🇷🇺
Saint-Petersburg, Russian Federation
First Saint-Petersburg State Medical University n.a. I.P. Pavlov
🇷🇺
Saint-Petersburg, Russian Federation
First Saint-Petersburg State Medical University n.a. I.P.
🇷🇺
Saint-Petersburg, Russian Federation
Samara Regional Clinical Oncology Dispensary
🇷🇺
Samara, Russian Federation
National Cancer Centre
🇸🇬
Singapore, Singapore
National University Hospital
🇸🇬
Singapore, Singapore
Parkway Cancer Centre
🇸🇬
Singapore, Singapore
Rondebosch Oncology Centre, Rondebosch Medical Centre
🇿🇦
Cape Town, South Africa
University of Witwatersrand Oncology
🇿🇦
Johannesburg, Gauteng, South Africa
OncoCare Cancer Centre
🇸🇬
Singapore, Singapore
Hospital General Universitario de Elche
🇪🇸
Elche, Alicante, Spain
Hospital Universitario Virgen Macarena
🇪🇸
Sevilla, Andalucia, Spain
Hospital Clinico Universitario Lozano Blesa
🇪🇸
Zaragoza, Aragon, Spain
Hospital Universitari Vall D'Hebron
🇪🇸
Barcelona, Spain
Hospital Universitario Insular de Gran Canaria
🇪🇸
Las Palmas de Gran Canaria, Spain
Hospital Ramon Y Cajal
🇪🇸
Madrid, Spain
Hospital Universitario Virgen de La Victoria
🇪🇸
Malaga, Spain
Luzerner Kantonsspital (LUKS)
🇨🇭
Luzern, Switzerland
Kantonsspital Winterthur
🇨🇭
Winterthur, Switzerland
Chang Gung Medical Foundation, Kaohsiung Branch
🇨🇳
Kaohsiung City, Taiwan
Taichung Veterans General Hospital, Comprehensive Cancer Center
🇨🇳
Taichung, Taiwan
China Medical University Hospital
🇨🇳
Taichung, Taiwan
City Multiple-Discipline Clinical Hospital #4,
🇺🇦
Dnipropetrovsk, Ukraine
Chang Gung Medical Foundation, LinKou Branch
🇨🇳
Taoyuan, Taiwan
Department of Oncology and Medical Radiology, SI "DMA of MOH, Ukraine
🇺🇦
Dnipropetrovsk, Ukraine
City Multiple-Discipline Clinical Hospital #4
🇺🇦
Dnipropetrovsk, Ukraine
Kyiv City Clinical Oncologic Center/Department of Chemotherapy
🇺🇦
Kyiv, Ukraine
Lviv State Oncologic Regional Treatment and Diagnostic Center
🇺🇦
Lviv, Ukraine
Addenbrooke's Hospital, Oncology Centre
🇬🇧
Cambridge, Cambridgeshire, United Kingdom
Lister Hospital
🇬🇧
Stevenage, Hertfordshire, United Kingdom
Mount Vernon Hospital, Mount Vernon Cancer Centre
🇬🇧
Northwood, Middlesex, United Kingdom
Ross Hall Hospital
🇬🇧
Glasgow, Scotland, United Kingdom
NHS Greater Glasgow and Clyde Health Board, Beatson West of Scotland Cancer Centre,
🇬🇧
Glasgow, Scotland, United Kingdom
Aberdeen Royal Infirmary
🇬🇧
Aberdeen, United Kingdom
The Christie Hospital NHS Foundation Trust, Department of Medical Oncology
🇬🇧
Manchester, United Kingdom
University of New Mexico Cancer Center
🇺🇸
Albuquerque, New Mexico, United States
Tower Hematology Oncology Medical Group
🇺🇸
Beverly Hills, California, United States
Ochsner Clinic Foundation
🇺🇸
New Orleans, Louisiana, United States
UNM Eye Clinic
🇺🇸
Albuquerque, New Mexico, United States
Maine Center for Cancer Medicine
🇺🇸
Scarborough, Maine, United States
Hematology-Oncology Associates of Northern New Jersey
🇺🇸
Morristown, New Jersey, United States
Long Island Jewish Medical Center
🇺🇸
New Hyde Park, New York, United States
Aichi cancer center central hospital
🇯🇵
Nagoya, Aichi, Japan
UT Southwestern University Hospital - Zale Lipshy
🇺🇸
Dallas, Texas, United States
Memorial Medical Center
🇺🇸
Las Cruces, New Mexico, United States
OHSU Knight Cancer Institute
🇺🇸
Tualatin, Oregon, United States
The Townsville Hospital
🇦🇺
Douglas, Queensland, Australia
Hospital Doce de Octubre
🇪🇸
Madrid, Spain
UNIVERSITÄTSMEDIZIN der Johannes Gutenberg-Universität Mainz
🇩🇪
Mainz, Germany
Kanagawa Cardiovascular and Respiratory Center
🇯🇵
Yokohama, Kanagawa, Japan
Tohoku University Hospital
🇯🇵
Sendai, Miyagi, Japan
Asan Medical Center
🇰🇷
Seoul, Korea, Republic of
Hospital Clinic I Provincial de Barcelona
🇪🇸
Barcelona, Catalunya, Spain