A Study Of Avelumab In Patients With Locally Advanced Or Metastatic Urothelial Cancer (JAVELIN Bladder 100)

• ClinicalTrials.gov Identifier: NCT02603432
• Recruitment Status: Completed
• First Posted: November 11, 2015
• Results First Posted: December 17, 2020
• Last Update Posted: March 27, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

The main purpose of this study is to compare maintenance treatment with avelumab plus best supportive care (BSC) with BSC alone, to determine if avelumab has an effect on survival in patients with locally advanced or metastatic urothelial cancer that did not worsen during or following completion of first-line chemotherapy.

Condition or disease	Intervention/treatment	Phase
Urothelial Cancer	Biological: Avelumab; Other: Best Supportive Care; Biological: Following the planned interim analysis for this study: Avelumab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 700 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A PHASE 3, MULTICENTER, MULTINATIONAL, RANDOMIZED, OPEN-LABEL, PARALLEL-ARM STUDY OF AVELUMAB (MSB0010718C) PLUS BEST SUPPORTIVE CARE VERSUS BEST SUPPORTIVE CARE ALONE AS A MAINTENANCE TREATMENT IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC UROTHELIAL CANCER WHOSE DISEASE DID NOT PROGRESS AFTER COMPLETION OF FIRST-LINE PLATINUM-CONTAINING CHEMOTHERAPY
• Actual Study Start Date: April 25, 2016
• Actual Primary Completion Date: October 21, 2019
• Actual Study Completion Date: March 28, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A; Avelumab plus Best Supportive Care (BSC)	Biological: Avelumab; 1 hour intravenous infusion every 2 weeks (Q2W) in 4 week cycles; Other: Best Supportive Care; BSC will be administered as deemed appropriate by the treating physician, and could include treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management (including palliative radiotherapy), etc. BSC does not include any active anti-tumor therapy, however local radiotherapy of isolated lesions with palliative intent is acceptable.
Arm B; Best Supportive Care (BSC) alone Following the planned interim analysis for this study, eligible patients in Arm B whose cancer has not worsened and are still in the "watch and wait" part of the study will be given the option to receive Avelumab plus BSC. Prior to this, Arm B patients received BSC alone. All patients who choose not to receive Avelumab will be discontinued.	Other: Best Supportive Care; BSC will be administered as deemed appropriate by the treating physician, and could include treatment with antibiotics, nutritional support, correction of metabolic disorders, optimal symptom control and pain management (including palliative radiotherapy), etc. BSC does not include any active anti-tumor therapy, however local radiotherapy of isolated lesions with palliative intent is acceptable.; Biological: Following the planned interim analysis for this study: Avelumab; 1 hour intravenous infusion every 2 weeks (Q2W) in 4 week cycles

Outcome Measures

Primary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: From randomization to discontinuation from the study, death or date of censoring, whichever occurred first (for a maximum duration of 41 months) ]
   Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.

Secondary Outcome Measures :

1. Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: From randomization to date of progression of disease, discontinuation from the study, death or date of censoring, whichever occurred first (for a maximum duration of 41 months) ]
   BICR assessed PFS: Duration from randomization until disease progression (PD) or death. PD as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was defined for target disease as at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was smallest on study). In addition to relative increase of 20%, sum must have also demonstrated an absolute increase of at least 5 millimeters. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. Appearance of any new unequivocal malignant lesion was also considered PD. Analysis was performed using Kaplan-Meier. PFS data was censored on date of last adequate tumor assessment for participants with no event (PD or death), who started new anti-cancer therapy prior to an event or with an event after 2 or more missing tumor assessments.
2. Progression-Free Survival (PFS) as Assessed by Investigator [ Time Frame: From randomization to date of progression of disease, discontinuation from the study, death or date of censoring, whichever occurred first (for a maximum duration of 41 months) ]
   Investigator assessed PFS: Duration from randomization to first documentation of PD or death, whichever occurred first. PD as per RECIST version 1.1 was defined for target disease as at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study (this included baseline sum if that was smallest on study). In addition to relative increase of 20%, sum must have also demonstrated an absolute increase of at least 5 mm. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. Appearance of any new unequivocal malignant lesion was also considered PD. Analysis was performed using Kaplan-Meier. PFS data was censored on date of last adequate tumor assessment for participants with no event (PD or death), who started a new anti-cancer therapy prior to an event or with an event after 2 or more missing tumor assessments.
3. Percentage of Participants With Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: From randomization to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (for a maximum duration of 41 months) ]
   BICR assessed objective response according to RECIST version 1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR). CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.
4. Percentage of Participants With Objective Response as Assessed by Investigator [ Time Frame: From randomization to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (for a maximum duration of 41 months) ]
   Investigator assessed objective response according to RECIST version 1.1, was defined as participants with confirmed best overall response of CR or PR. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. A CR also required normalization of tumor marker levels and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.
5. Time to Tumor Response (TTR) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: From the date of randomization to the first documentation of objective response (CR or PR) (for a maximum duration of 41 months) ]
   TTR was defined, for participants with an objective response as the time from 'start date' to the first documentation of objective tumor response (CR or PR), which was confirmed subsequently. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.
6. Time to Tumor Response (TTR) as Assessed by Investigator [ Time Frame: From the date of randomization to the first documentation of objective response (CR or PR) (for a maximum duration of 41 months) ]
   TTR was defined, for participants with an objective response as the time from 'start date' to the first documentation of objective tumor response (CR or PR). CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. A CR also required normalization of tumor marker levels and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions.
7. Duration of Response (DOR) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (for a maximum duration of 41 months) ]
   BICR assessed DOR: time from first documentation of OR (confirmed CR or PR) to date of first documentation of PD or death due to any cause. As per RECIST version 1.1, CR: complete disappearance of all target and non-target lesions, with exception of nodal disease sustained for 4 weeks. Any pathological lymph nodes reduced in short axis to <10 mm. PR: at least 30% decrease in sum of longest dimensions of target lesions taking as reference baseline sum longest dimensions. PD for target disease: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study and relative increase of 20%, sum also demonstrated absolute increase of at least 5 mm. PD for non-target disease: unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. Appearance of any new unequivocal malignant lesion was also considered PD.
8. Duration of Response (DOR) as Assessed by Investigator [ Time Frame: First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (for a maximum duration of 41 months) ]
   Investigator assessed DOR: time from first documentation of OR (confirmed CR or PR) to date of first documentation of PD or death due to any cause. As per RECIST version 1.1, CR: complete disappearance of all target and non-target lesions, with exception of nodal disease sustained for 4 weeks. Additionally, normalization of tumor marker levels and any pathological lymph nodes reduced in short axis to <10 mm. PR: at least 30% decrease in sum of longest dimensions of target lesions taking as reference baseline sum longest dimensions. PD for target disease: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study and relative increase of 20%, sum also demonstrated absolute increase of at least 5 mm. PD for non-target disease: unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy. Appearance of any new unequivocal malignant lesion was also considered PD.
9. Percentage of Participants With Disease Control (DC) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: From randomization to PD, death or start of new anti-cancer therapy (for a maximum duration of 41 months) ]
   Disease Control (DC) was defined as a best overall response of CR, PR, non-CR/non-PD or stable disease (SD) as assessed by BICR. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. Non-CR/Non-PD was defined as persistence of any non-target lesions and/or tumor marker level above the normal limits. SD was defined as not to qualify for CR, PR or PD for target lesions and followed PR only if the sum increased by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds.
10. Percentage of Participants With Disease Control (DC) as Assessed by Investigator [ Time Frame: From randomization to PD, death or start of new anti-cancer therapy (for a maximum duration of 41 months) ]
    DC was defined as a best overall response of CR, PR, non-CR/non-PD or SD as assessed by Investigator. CR was defined as complete disappearance of all target and non-target lesions, with the exception of nodal disease and sustained for at least 4 weeks. Additionally, normalization of tumor marker levels and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. Non-CR/Non-PD was defined as persistence of any non-target lesions and/or tumor marker level above the normal limits. SD was defined as not to qualify for CR, PR or PD for target lesions and followed PR only if the sum increased by less than 20% from the nadir, but enough that a previously documented 30% decrease no longer holds.
11. Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 [ Time Frame: For "Avelumab + Best Supportive Care (BSC)'' group: Day1 up to 90 days after last dose of study drug; for BSC group: Day1 up to 90 days after EOT visit (for a maximum duration of up to approximately 70 months for both groups) ]
    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent AEs are events between first dose of study drug and up to 90 days after last dose of study drug or end of treatment (EOT) visit, that were absent before treatment or that worsened relative to pretreatment state.
12. Number of Participants With Laboratory Abnormalities Greater Than or Equal to (>=) Grade 3 (G3), Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03 [ Time Frame: For "Avelumab + Best Supportive Care (BSC)'' group: Day1 up to 90 days after last dose of study drug; for BSC group: Day1 up to 90 days after EOT visit (for a maximum duration of up to approximately 70 months for both groups) ]
    Hematology (Anemia G3: hemoglobin<8.0 grams per deciliter [g/dL],<4.9 millimoles (mmol)/liter (L),<80 g/L, transfusion indicated, Grade 4 [G4]: life-threatening consequences, urgent intervention indicated, Grade 5 [G5]: death; platelet count decreased-G3:<50.0 to 25.0*10^9/L, G4: <25.0*10^9/L; lymphocyte count decreased-G3:<0.5-0.2*10^9/L, G4:<0.2*10^9/L; neutrophil count decreased-G3:<1.0 to 0.5*10^9 /L, G4:<0.5*10^9/L). Chemistry (creatinine increased-G3:>3.0 to 6.0*upper limit of normal [ULN], G4:>6.0*ULN; serum amylase increased, lipase increased-G3:>2.0- 5.0*ULN, G4:>5.0*ULN. Aspartate aminotransferase [AST], alanine aminotransferase [ALT]-G3:>5.0 to 20.0*ULN, G4:>20.0*ULN]. Blood bilirubin increased-[G3:>3.0 to 10.0*ULN, G4:>10.0*ULN], Creatine phosphokinase [CPK] increased- [G3:>5.0 to 10.0*ULN, G4:>10.0*ULN], Hyperglycemia-[G3:>250 to 500 mg/dL; >13.9 to 27.8 mmol/L hospitalization indicated, G4:>500 mg/DL; >27.8 mmol/L life-threatening consequences]).
13. Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit [ Time Frame: Baseline (Day [D] 1 of Cycle [C] 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7 , EOT visit (for a maximum duration of 41 months) (each cycle=28 days) ]
    Vital signs included blood pressure and pulse rate. Blood pressure included sitting diastolic blood pressure (DBP) and sitting systolic blood pressure (SBP).
14. Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycle 2, 3, 4, 5, 6, 7 and End of Treatment (EOT) Visit [ Time Frame: Baseline (Day [D] 1 of Cycle [C] 1), Day 1 of Cycle 2, 3, 4, 5, 6, 7 , EOT visit (for a maximum duration of 41 months) (each cycle=28 days) ]
    Vital signs included blood pressure and pulse rate. Changes from baseline in sitting pulse rate were summarized.
15. Maximum Plasma Concentration (Cmax) of Avelumab [ Time Frame: End of avelumab infusion on Day 1 of Cycle 1, 2, 3, 5, 7, 9, 11, 13 and Day 15 of Cycle 1, 2, 3 (each cycle=28 days) ]
    The Lower Limit of Quantitation (LLQ) of avelumab was 0.20 micrograms (mcg)/milliliter (mL). Data for this outcome measure was not collected for reporting group "Best Supportive Care", since avelumab was not administered in this arm.
16. Predose Plasma Concentration (Ctrough) of Avelumab [ Time Frame: Pre-dose (0 hour) on Day 1 of Cycle 1, 2, 3, 5, 7, 9, 11, 13 and Day 15 of Cycle 1, 2, 3 (each cycle=28 days) ]
    The LLQ of avelumab was 0.20 mcg/mL. Data for this outcome measure was not collected for reporting group "Best Supportive Care", since avelumab was not administered in this arm.
17. Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status [ Time Frame: From randomization up to the 30-Day Follow-up visit (maximum duration of up to approximately 68 months) ]
    ADA against avelumab in serum samples was determined and reported separately for ADA never positive and ADA ever positive participants. Participants were considered ADA ever-positive if they had at least one positive ADA result at any time point during study and were otherwise considered negative. Data for this outcome measure was not planned to be collected and analyzed for reporting arm "Best Supportive Care", since avelumab was not administered in this arm.
18. Number of ADA Ever Positive Participants For Each Serum of ADA Titers for Avelumab [ Time Frame: From randomization up to the 30-Day Follow-up visit (maximum duration of up to approximately 68 months) ]
    Serum samples were assayed for ADA using a validated analytical method. Number of ADA ever positive participants for each serum of ADA titer (60, 180, 540, 1620, 4860, 14580, and 131220) are reported.
19. Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never Positive and Ever Positive Status [ Time Frame: From randomization up to the 30-Day Follow-up visit (maximum duration of up to approximately 68 months) ]
    nAb against avelumab in serum samples was determined and reported separately for nAb never positive and nAb ever positive participants. Participants were considered nAb ever-positive if they had at least one positive nAb result at any time point during study and were otherwise considered negative.
20. Number of Participants With Programmed Death Receptor-1 Ligand 1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC) [ Time Frame: Up to 41 months at the time of the analysis ]
    PD-L1 assessment was performed using immunohistochemistry on pre-treatment tumor tissue samples. Participants were classified as having PD-L1 -positive status if at least one of the following three criteria were met: at least 25% of tumor cells stained for PD-L1, at least 25% of immune cells stained for PD-L1 if more than 1% of the tumor area contained immune cells, or 100% of immune cells stained for PD-L1 if no more than 1% of the tumor area contained immune cells.
21. Number of Participants With Cluster of Differentiation 8 (CD8) T Lymphocytes (Cytotoxic T Lymphocytes) [ Time Frame: Up to approximately 60 months ]
    Number of Participants With CD8 T Lymphocytes (Cytotoxic T lymphocytes) were presented in this outcome.
22. Change From Baseline in National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (NCCN-FACT) Bladder Symptom Index- 18 (FBlSI-18) Score at Day 1 of Cycle 6 [ Time Frame: Baseline, Day 1 of Cycle 6 (1 cycle=28 days) ]
    NCCN-FACT FBlSI-18 is an 18-item participant completed questionnaire, designed to assess impact of cancer therapy on urothelial cancer-related symptoms and quality of life based on numerical point scoring of symptoms/concerns. It included four subscales: Disease related symptoms- physical subscale with 9 items, disease related symptoms- emotional subscale with 2 items, treatment side effects subscale with 5 items and general function/well-being subscale with 2 items. Participants rated their level of symptoms for each item using 5-point scale ranging from 0=not at all to 4=very much. Items that were negatively framed, and the scores were reversed for analysis so that higher scores= good quality of life. Overall score: total of 18 items, ranging from 0=severely symptomatic to 72=asymptomatic. Higher scores= better functioning or lower symptom burden.
23. Time to Deterioration (TTD) Based on National Comprehensive Cancer Network- Functional Assessment of Cancer Therapy (NCCN-FACT) Bladder Symptom Index- 18 (FBlSI-18) Disease Related Symptoms-Physical Subscale (DRS-P) Scores [ Time Frame: From randomization up to the 90-Day Follow-up Visit (maximum duration of up to 41 months) ]
    NCCN-FACT FBlSI-18: an 18-item participant completed questionnaire, designed to assess impact of cancer therapy on urothelial cancer-related symptoms and quality of life based on numerical point scoring of symptoms/concerns. It included four subscales: Disease related symptoms-physical subscale with 9 items, disease related symptoms-emotional subscale with 2 items, treatment side effects subscale with 5 items, general function/well-being subscale with 2 items. Participants rated their level of symptoms for each item using 5-point scale ranging: 0=not at all to 4=very much. For items negatively framed, scores were reversed for analysis so that higher scores= good quality of life. DRS-P score: total 9 items, ranging from 0=severely symptomatic to 36= asymptomatic. Higher scores=better functioning or lower symptom burden. TTD: time from randomization to first time participant's score showed 3 point or greater decrease from baseline in FBlSI-DRS-P subscale for 2 consecutive assessments.
24. Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Utility Score at Cycle 6 [ Time Frame: Baseline, Day 1 of Cycle 6 (1 cycle=28 days) ]
    The EQ-5D-5L was a 6-item participant-completed questionnaire designed to assess health status in terms of a single utility score. There were 2 components to the EQ-5D-5L, a Health State Profile which had 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 Visual Analogue Scale (VAS) in which participant rated their overall health status from 0 (worst imaginable) to 100 (best imaginable). Published UK weights was used to create a single summary utility score. Utility scores range from -0.594 to 1, with low scores representing lower health status.
25. Change From Baseline in European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) - Visual Analog Scale (VAS) Score at Cycle 6 [ Time Frame: Baseline, Day 1 of Cycle 6 (1 cycle=28 days) ]
    The EQ-5D-5L was a 6-item participant-completed questionnaire designed to assess health status in terms of a single utility score. There were 2 components to the EQ-5D-5L, a Health State Profile which had 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 Visual Analogue Scale (VAS) in which participant rated their overall health status from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically confirmed, unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium
• Stage IV disease at the start of first-line chemotherapy
• Measurable disease (per RECIST v1.1) prior to the start of first-line chemotherapy
• Prior first-line chemotherapy must have consisted of at least 4 cycles and no more than 6 cycles of gemcitabine + cisplatin and/or gemcitabine + carboplatin
• No evidence of progressive disease following completion of first-line chemotherapy (i.e., ongoing CR, PR, or SD per RECIST v1.1 guidelines )

Exclusion Criteria:

• Prior adjuvant or neoadjuvant systemic therapy within 12 months of randomization
• Prior immunotherapy with IL-2, IFN-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA 4 antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
• Persisting toxicity related to prior therapy (Grade >1 NCI CTCAE v4.0); however, alopecia, sensory neuropathy (Grade 2 or less), or other (Grade 2 or less) adverse events not constituting a safety risk based on the investigator's judgement are acceptable.
• Patients with known symptomatic central nervous system (CNS) metastases requiring steroids
• Diagnosis of any other malignancy within 5 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the breast or of the cervix, low grade prostate cancer on surveillance without any plans for treatment intervention, or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms.

Contacts and Locations

Locations

United States, Colorado

Anschutz Cancer Center Pavilion Pharmacy

Aurora, Colorado, United States, 80045

University of Colorado Cancer Center

Aurora, Colorado, United States, 80045

University of Colorado Denver, CTO (CTRC)

Aurora, Colorado, United States, 80045

University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP)

Aurora, Colorado, United States, 80045

University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP)

Aurora, Colorado, United States, 80045

United States, Connecticut

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, United States, 06510

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, United States, 06510

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Minnesota

University of Minnesota Medical Center

Minneapolis, Minnesota, United States, 55455

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Ohio

Cleveland Clinic Taussing Cancer Center

Cleveland, Ohio, United States, 44106

Cleveland Clinic Taussing Cancer Center

Cleveland, Ohio, United States, 44160

Cleveland Clinic Foundation

Cleveland, Ohio, United States, 44195

Cleveland Clinic Taussing Cancer Center

Cleveland, Ohio, United States, 44195

United States, Virginia

Inova Schar Cancer Institute Infusion Pharmacy

Fairfax, Virginia, United States, 22031

Inova Schar Cancer Institute

Fairfax, Virginia, United States, 22031

United States, Washington

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109-1023

Seattle Cancer Care Alliance

Seattle, Washington, United States, 98109

University of Washington Medical Center

Seattle, Washington, United States, 98195

Argentina

Centro de Investigacion Pergamino S.A.

Pergamino, Buenos Aires, Argentina, B2700CPM

Fundación CENIT para la Investigación en Neurociencias

Caba, Argentina, C1125ABD

GP Diagnostico SRL

La Rioja, Argentina, 5300

Hospital Regional Dr. Enrique Vera Barros

La Rioja, Argentina, 5300

Instituto del Diagnostico

La Rioja, Argentina, 5300

Centro Oncologico Riojano Integral (Cori)

La Rioja, Argentina, F5300COE

Australia, New South Wales

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia, 2050

Concord Hospital

Concord, New South Wales, Australia, 2139

Dubbo Base Hospital

Dubbo, New South Wales, Australia, 2830

Ramsay Pharmacy

Kogarah, New South Wales, Australia, 2217

St George Private Hospital

Kogarah, New South Wales, Australia, 2217

Epic Pharmacy

Lismore, New South Wales, Australia, 2480

North Coast Radiology St Vincents

Lismore, New South Wales, Australia, 2480

Northern Rivers Pathology Service

Lismore, New South Wales, Australia, 2480

St Vincent's Pathology Lismore

Lismore, New South Wales, Australia, 2480

Macquarie Medical Imaging

Macquarie University, New South Wales, Australia, 2109

Macquarie University Hospital Pharmacy

Macquarie University, New South Wales, Australia, 2109

Macquarie University

Macquarie University, New South Wales, Australia, 2109

The Murwillumbah Hospital

Murwillubah, New South Wales, Australia, 2484

The Tweed Hospital Pharmacy Department

Tweed Heads, New South Wales, Australia, 2485

The Tweed Hospital

Tweed Heads, New South Wales, Australia, 2485

Australia, Queensland

Icon Cancer Care Wesley

Auchenflower, Queensland, Australia, 4066

River City Pharmacy

Auchenflower, Queensland, Australia, 4066

Oncology Pharmacy

Birtinya, Queensland, Australia, 4575

Sunshine Coast University Hospital

Birtinya, Queensland, Australia, 4575

Icon Cancer Care Chermside

Chermside, Queensland, Australia, 4032

The Townsville Hospital

Douglas, Queensland, Australia, 4814

Slade Health

Geebung, Queensland, Australia, 4034

Icon Cancer Care South Brisbane

South Brisbane, Queensland, Australia, 4101

Icon Cancer Care

South Brisbane, Queensland, Australia, 4101

Integrated Clinical Oncology Network (ICON) Corporate Office

South Brisbane, Queensland, Australia, 4101

Icon Cancer Care Southport

Southport, Queensland, Australia, 4215

Australia, South Australia

Flinders Medical Centre

Bedford Park, South Australia, Australia, 5042

SA Pharmacy, Level 3 Pharmacy

Bedford Park, South Australia, Australia, 5042

Adelaide Cancer Centre

Kurralta Park, South Australia, Australia, 5037

Ashford Cancer Centre Research

Kurralta park, South Australia, Australia, 5037

Cancer Care SA Pty Ltd

Kurralta Park, South Australia, Australia, 5037

Icon Cancer Care SA trading as Icon Pharmacy Adelaide

Kurralta Park, South Australia, Australia, 5037

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia, 5011

Australia, Victoria

BHS Diagnostic Services

Ballarat, Victoria, Australia, 3350

Lake Imaging

Ballarat, Victoria, Australia, 3350

Ballarat Oncology & Haematology Services

Ballarat, Victoria, Australia, 3355

Box Hill Hospital - Pharmacy Department, Bulding B, Loading Dock (access via Thames St)

Box Hill, Victoria, Australia, 3128

Box Hill Hospital

Box Hill, Victoria, Australia, 3128

Eastern Health Clinical School

Box Hill, Victoria, Australia, 3128

Monash Medical Centre

Clayton, Victoria, Australia, 3168

Monash Medical Centre

East Bentleigh, Victoria, Australia, 3165

Moorabbin Radiology

East Bentleigh, Victoria, Australia, 3165

Ballarat Day Procedure Centre

Wendouree, Victoria, Australia, 3355

Ballarat Oncology & Haematology Services

Wendouree, Victoria, Australia, 3355

Nova Pharmacy

Wendouree, Victoria, Australia, 3355

Australia, Western Australia

Fiona Stanley Hospital

Murdoch, Western Australia, Australia, 6150

St John of God Murdoch Hospital

Murdoch, Western Australia, Australia, 6150

Australia

Slade Health

Mount Waverley, Australia, 3149

Macquarie Heart

New South Wales, Australia, 2109

Belgium

AZ Klina - Apotheek

Brasschaat, Belgium, 2930

AZ Klina

Brasschaat, Belgium, 2930

Hôpital Erasme

Brussels, Belgium, 1070

Hôpital Erasme

Bruxelles, Belgium, 1070

UZ Gent

Gent, Belgium, 9000

UZ Gent

Ghent, Belgium, 9000

AZ Groeninge

Kortrijk, Belgium, 8500

CHU de Liège

Liège, Belgium, 4000

GZA Sint-Augustinus

Wilrijk, Belgium, 2610

Brazil

Hospital da Bahia

Salvador, BA, Brazil, 41820-011

CENOB Centro de Oncologia da Bahia S/S Ltda. / Oncovida

Salvador, BA, Brazil, 41820-021

ONCOSITE - Centro de Pesquisa Clinica em Oncologia

Ijui, RIO Grande DO SUL, Brazil, 98700-000

Hospital Mãe de Deus/Aesc

Porto Alegre, RIO Grande DO SUL, Brazil, 90110-270

Instituto Nacional de Câncer - INCA

Rio de Janeiro, RJ, Brazil, 20230-130

Associacao Hospital de Caridade Ijui

Ijui, RS, Brazil, 98700-000

Associação Educadora São Carlos - AESC / Hospital Mãe de Deus

Porto Alegre, RS, Brazil, 90110-000

Associação Educadora São Carlos - AESC / Hospital Mãe de Deus - Ambulatório Quimioterapia

Porto Alegre, RS, Brazil, 90110-270

Associação Educadora São Carlos - AESC / Hospital Mãe de Deus - Centro de Abastecimento Farmaceut

Porto Alegre, RS, Brazil, 90110-270

Associação Educadora São Carlos - AESC / Hospital Mãe de Deus - Farmácia Oncológica

Porto Alegre, RS, Brazil, 90110-270

Associação Educadora São Carlos - AESC / Hospital Mãe de Deus

Porto Alegre, RS, Brazil, 90110-270

Uniao Brasileira de Educacao e Assistencia / Hospital Sao Lucas da PUCRS

Porto Alegre, RS, Brazil, 90610-000

Fundação FPio XII Barretos

Barretos, SP, Brazil, 14784-400

Fundação Pio XII Barretos

Barretos, SP, Brazil, 14784-400

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto

Sao Jose do Rio Preto, SP, Brazil, 15090-000

Fundacao Faculdade de Medicina / Instituto do Cancer do Estado de Sao Paulo - ICESP

Sao Paulo, SP, Brazil, 01246-000

Hospital Alemao Oswaldo Cruz

Sao Paulo, SP, Brazil, 01323-903

Hospital das Clinicas da Faculdade de Medicina da USP - HCFMUSP

Sao Paulo, SP, Brazil, 05403-900

Centro Integrado de Pesquisa Clinica - CIP

São José do Rio Preto, SP, Brazil, 15090-000

Sociedade Beneficente de Senhoras Hospital Sírio Libanês

São Paulo, SP, Brazil, 01308-050

Sociedade Beneficente de Senhoras Hospital Sírio Libanês

São Paulo, SP, Brazil, 01308-060

Hospital Israelita Albert Einstein - SP

São Paulo, SP, Brazil, 05652-900

Sociedade Beneficente de Senhoras Hospital Sírio Libanês/ Instituo Sirio Libanes de Ensino e Pesqu

São Paulo, Brazil, 01308-060

Canada, Ontario

William Osler Health System

Brampton, Ontario, Canada, L6R 3J7

Princess Margaret Cancer Centre

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

CHUM - Centre Hospitalier de l'Universite de Montreal

Montréal, Quebec, Canada, H2X 3E4

Czechia

Fakultni nemocnice u sv. Anny v Brne

Brno, Ceska Republika, Czechia, 656 91

Fakultni nemocnice Brno

Brno, Czechia, 625 00

Fakultni nemocnice u sv. Anny v Brne

Brno, Czechia, 656 91

Fakultni nemocnice u sv.Anny v Brne

Brno, Czechia, 656 91

Nemocnice Horovice, NH Hospital a.s.

Horovice, Czechia, 268 31

Nemocnice Horovice

Horovice, Czechia, 268 31

Denmark

Aalborg Universitetshospital Syd

Aalborg, Denmark, 9000

Aalborg Universitetshospital

Aalborg, Denmark, 9000

Sygehusapoteket Aalborg

Aalborg, Denmark, 9000

Aarhus Universitetshospital

Aarhus C, Denmark, 8000

Aarhus Universitetshospital

Aarhus N, Denmark, 8200

CT-Klinikken A/S

Aarhus N, Denmark, 8200

Rigshospitalet, Onkologisk Klinik, afsnit 5073

Copenhagen OE, Denmark, 2100

Herlev Hospital

Herlev, Denmark, 2730

Herlev og Gentofte Hospital

Herlev, Denmark, 2730

Klinik for Klinisk Fysiologi,Nuklearmedicin og PET

København Ø, Denmark, 2100

Rigshospitalet

København Ø, Denmark, 2100

Odense Universitetshospital

Odense C, Denmark, 5000

Odense Universitetshospital

Odense, Denmark, 5000

France

Groupe hospitalier Pitie Saleptriere

Paris, Cedex 13, France, 75651

Institut de cancérologie de l'Ouest - Site Paul Papin

Angers Cedex 02, France, 49055

Institut de cancérologie de l'Ouest - Site Paul Papin

Angers, France, 49100

Centre d'Oncologie et de Radiothérapie du Pays-Basque

Bayonne, France, 64100

Clinique CAPIO Belharra

Bayonne, France, 64100

Hôpital Jean Minjoz

BESANCON cedex, France, 25030

CHU Besançon - Pharmacie Unite Essais cliniques

Besançon, France, 25030

CHU Besançon

Besançon, France, 25030

Hôpital Henri Mondor

CRÉTEIL Cedex, France, 94010

Hôpital Privé Toulon-Hyères - Clinique Sainte Marguerite

Hyères, France, 83400

Clinique Victor Hugo

Le Mans, France, 72015

Centre Oscar Lambret

Lille cedex, France, 59020

Centre Oscar Lambret

Lille, France, 59000

Centre Leon Berard

Lyon cedex 8, France, 69373

Centre Léon Berard

LYON cedex 8, France, 69373

Hopital La Conception

Marseille cedex 5, France, 13285

Institut Paoli Calmettes

Marseille Cedex 9, France, 13273

Institut Paoli Calmettes

Marseille, France, 13009

Hopital de La Timone

Marseille, France, 13385 cedex 05

Hopital de La Timone

Marseille, France, 13385

CHU Nimes - Institut de Cancerologie du Gard

Nimes Cedex 9, France, 30029

CHU Nimes

Nimes Cedex 9, France, 30029

CHU Nimes - Hopital Caremeau

Nimes, France, 30000

Groupe Hospitalier Pitié Salpêtrière

PARIS cedex 13, France, 75651

Groupe Hospitalier Pitié Salpêtrière

Paris, France, 75013

Centre Eugene Marquis

Rennes Cedex, France, 35042

Centre Henri Becquerel

Rouen Cedex 1, France, 76038

CHU de Rouen - Hôpital Charles Nicolle

Rouen, France, 76031

CHU de Rouen

Rouen, France, 76031

Institut de Cancérologie de l'Ouest - Centre René Gauducheau

Saint Herblain Cedex, France, 44805

Centre de Radiothérapie - Clinique Sainte Anne

Strasbourg, France, 67000

Clinique Sainte Anne

Strasbourg, France, 67000

Hopital Foch -Pharmacie

Suresnes, France, 92150

Hopital Foch

Suresnes, France, 92151

Institut Gustave Roussy

Villejuif cedex, France, 94805

Institut Gustave Roussy

Villejuif, France, 94805

Greece

Medical Center of Athens

Marousi, Athens, Greece, 15125

Metropolitan General Hospital

Athens, PC, Greece, 11562

Sotiria General Chest Disease Hospital

Athens, Greece, 11527

Alexandra General Hospital, Oncology Department

Athens, Greece, 11528

University General Hospital of Patras, Division of Oncology

Patra, Greece, 26504

EUROMEDICA General Clinic of Thessaloniki

Thessaloniki, Greece, 546 45

Hong Kong

Department of Clinical Oncology

Hong Kong, Hong Kong

Hungary

Kaposvári Egyetem Egészségügyi Centrum

Kaposvár, Hungary, 7400

Somogy Megyei Kaposi Mór Oktató Kórház

Kaposvár, Hungary, 7400

India

Dr Ram Manohar Lohia (RML) Hospital & PGI MER

New Delhi, Delhi, India, 110001

CIMS Cancer, Care Institute of Medical Sciences, CIMS Hospital

Ahmedabad, Gujarat, India, 380060

Sahyadri Super Speciality Hospital

Pune, Maharashtra, India, 411004

Apollo Hospitals

Hyderabad, Telangana, India, 500096

Medica Superspecialty hospital

Kolkata, WEST Bengal, India, 700099

Rajiv Gandhi Cancer Institute And Research Centre

Delhi, India, 110085

Israel

Hadassah University Hospital

Kiryat Hadassah, Jerusalem, Israel, 91120

The Chaim Sheba Medical Center

Tel-Hashomer, Ramat - GAN, Israel, 5265601

Assaf Harofe MC

Beer Yaakov, Israel, 70300

Rambam Health Care Campus

Haifa, Israel, 31096

The Chaim Sheba Medical Center

Ramat - Gan, Israel, 5265601

Italy

Farmacia Ospedaliera

Candiolo, (torino), Italy, 10060

AOU Ospedali Riuniti di Ancona

Torrette, Ancona, Italy, 60126

U.O. Anatomia Patologica

Forli, Forli-cesena, Italy, 47121

U.O. Radiologia

Forli, Forli-cesena, Italy, 47121

U.O.S. Medicina Nucleare

Forli, Forli-cesena, Italy, 47121

Farmacia Oncologica

Meldola, Forli-cesena, Italy, 47014

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"

Meldola, Forli-cesena, Italy, 47014

U.O.C. Farmacia

Genova, Genoa, Italy, 16132

IRCCS Ospedale Policlinico San Martino

Genova, Liguria, Italy, 16132

Farmacia Studi Clinici

Rozzano, Milan, Italy, 20089

Istituto Clinico Humanitas

Rozzano, Milan, Italy, 20089

AUSL della Romagna - RAVENNA, Presidio Ospedaliero di Faenza

Faenza, Ravenna, Italy, 48018

Presidio Ospedaliero di Lugo

Lugo, Ravenna, Italy, 48022

Fondazione del Piemonte per l'Oncologia - IRCCS Candiolo

Candiolo, Torino, Italy, 10060

Farmacia Ospedaliera

Arezzo, Italy, 52100

Presidio Ospedaliero San Donato

Arezzo, Italy, 52100

Centro di Riferimento Oncologico - IRCCS

Aviano (PN), Italy, 33081

S.O.C. di Farmacia

Aviano (PN), Italy, 33081

Azienda Ospedaliero-Universitaria Policlinico S.Orsola Malpighi

Bologna, Italy, 40138

U.O. Farmacia Clinica - IDS

Bologna, Italy, 40138

Fondazione IRCCS Istituto Nazionale Dei Tumori

Milan, Italy, 20133

SC Farmacia

Milan, Italy, 20133

Instituto Europeo di Oncologia

Milan, Italy, 20141

Servizio di Farmacia

Milan, Italy, 20141

Azienda Ospedaliera di Rilievo Nazionale "A. Cardarelli"

Naples, Italy, 80131

UOSC Farmacia

Naples, Italy, 80131

Istituto Nazionale per lo Studio e la Cura dei Tumori, IRCCS Fondazione Giovanni Pascale

Napoli, Italy, 80131

S.C. Farmacia Ospedaliera

Napoli, Italy, 80131

A.O.U. Pisana Ospedale S. Chiara

Pisa, Italy, 56126

Presidio Ospedaliero di Ravenna

Ravenna, Italy, 48121

Servizio Farmacia Ospedaliera - Farmacia Oncologica

Ravenna, Italy, 48121

Azienda Ospedaliera San Camillo Forlanini_Oncologia Medica

Rome, Italy, 00152

U.O.C. Farmacia

Rome, Italy, 00152

Azienda Ospedaliera S. Maria di Terni

Terni, Italy, 05100

S.C. Farmacia Interna

Terni, Italy, 05100

Japan

Nagoya University Hospital

Nagoya, Aichi, Japan, 466-8560

Hirosaki University School of Medicine & Hospital

Hirosaki, Aomori, Japan, 036-8563

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, Japan, 791-0280

Gunma Prefectural Cancer Center

Ota, Gunma, Japan, 373-8550

National Hospital Organization hokkaido Cancer Center

Sapporo,, Hokkaido, Japan, 0030804

Hokkaido University Hospital

Sapporo, Hokkaido, Japan, 060-8648

Kobe City Medical Center General Hospital

Kobe-city, Hyogo, Japan, 650-0047

Tsukuba Medical Center Hospital

Tsukuba, Ibaraki, Japan, 305-8558

Iwate Medical University Hospital

Shiwa-gun, Iwate, Japan, 028-3695

National Hospital Organization Sagamihara National Hospital

Sagamihara, Kanagawa, Japan, 252-0392

Kanagawa cancer center

Yokohama, Kanagawa, Japan, 241-8515

Kindai University Hospital

Osakasayama, Osaka, Japan, 589-8511

Saitama Medical University International Medical Center

Hidaka, Saitama, Japan, 350-1298

Dokkyo Medical University Saitama Medical Center

Koshigaya, Saitama, Japan, 343-8555

Hamamatsu University School of Medicine, University Hospital

Hamamatsu, Shizuoka, Japan, 431-3192

Nihon University Itabashi Hospital

Itabashi-ku, Tokyo, Japan, 173-8610

The Cancer Institute Hospital of JFCR

Koto-Ku, Tokyo, Japan, 135-8550

Keio University Hospital

Shinjuku-Ku, Tokyo, Japan, 160-8582

Yamaguchi University Hospital

Ube, Yamaguchi, Japan, 755-8505

Chiba Cancer Center

Chiba, Japan, 260-8717

National Hospital Organization Kyushu Cancer Center

Fukuoka, Japan, 811-1395

Kyushu University Hospital

Fukuoka, Japan, 812-8582

Hiroshima City Hiroshima Citizens Hospital

Hiroshima, Japan, 730-8518

Kagoshima University Hospital

Kagoshima, Japan, 890-8520

National Hospital Organization Kumamoto Medical Center

Kumamoto, Japan, 860-0008

Niigata University Medical & Dental Hospital

Niigata, Japan, 951-8520

Osaka City University Hospital

Osaka, Japan, 545-8586

Tokushima University Hospital

Tokushima, Japan, 770-8503

Yamagata University Hospital

Yamagata, Japan, 990-9585

Korea, Republic of

National Cancer Center - Clinical Trial Pharmacy

Goyang-si, Gyeonggi-do, Korea, Republic of, 10408

National Cancer Center Urology center for Prostate Cancer

Goyang-si, Gyeonggi-do, Korea, Republic of, 10408

Seoul National University Bundang Hospital, Clinical Pharmacy

Seongnam-si, Gyeonggido, Korea, Republic of, 13620

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido, Korea, Republic of, 13620

Chungnam National University Hospital, Clinical Pharmacy

Daejeon, Korea, Republic of, 35015

Chungnam National University Hospital

Daejeon, Korea, Republic of, 35015

Severance Hospital Yonsei University Health System

Seoul, Korea, Republic of, 03722

Asan Medical Center - Clinical Trial Pharmacy

Seoul, Korea, Republic of, 05505

Asan Medical Center

Seoul, Korea, Republic of, 05505

Samsung Medical Center Clinical Trial Pharmacy

Seoul, Korea, Republic of, 06351

Samsung Medical Center

Seoul, Korea, Republic of, 06351

Mexico

Instituto Nacional de Cancerologia

Mexico, Ciudad DE Mexico, Mexico, 14080

Phylasis Clinicas Research S. de R.L. de C.V.

Cuautitlan Izcalli, Estado DE Mexico, Mexico, 54769

Centro de Investigación Clínica de Leon S.C.

Leon, Guanajuato, Mexico, 37520

Hospital Médica Campestre (Administradora Hospitalaria S.A de C.V.)

León, Guanajuato, Mexico, 37180

Netherlands

Rijnstate Arnhem

Arnhem, Netherlands, 6815 AD

Ziekenhuis Rijnstate

Arnhem, Netherlands, 6815 AD

St Apotheek der Haarlemse Ziekenhuizen

Haarlem, Netherlands, 2035 RC

Spaarne Gasthuis

Hoofddorp, Netherlands, 2134 TM

Maastricht University Medical Center

Maastricht, Netherlands, 6229 HX

Radboud University Medical Center

Nijmegen, Netherlands, 6525 GA

Radboudumc

Nijmegen, Netherlands, 6525 GA

New Zealand

Auckland City Hospital Pharmacy

Grafton, Auckland, New Zealand, 1023

Auckland City Hospital

Grafton, Auckland, New Zealand, 1142

Slade Health Inward Goods

Auckalnd, New Zealand, 1026

Christchurch Hospital

Christchurch, New Zealand, 8140

Waikato Hospital

Hamilton, New Zealand, 3240

Norway

Akershus University Hospital

Lorenskog, Norway, 1478

Sykehusapoteket HF 23 Lørenskog

Lorenskog, Norway, 1478

Sykehusapoteket HF 23 Lørenskog

Nordbyhagen, Norway, 1474

Sykehusapoteket Lorenskog

Nordbyhagen, Norway, 1474

Bildediagnostisk avdeling

Nordbyhagen, Norway, 1478

Stavanger University Hospital

Stavanger, Norway, 4011

Poland

Centralny Szpital Kliniczny MSWiA w Warszawie

Warsaw, Masovian, Poland, 02-507

Centralny Szpital Kliniczny MSWiA w Warszawie

Warszawa, Masovian, Poland, 02-507

Centralny Szpital Kliniczny MSWiA

Warszawa, Masovian, Poland, 02-507

Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z Dukli

Lublin, Poland, 20-090

Lecznice CITOMED Sp. z o.o.

Torun, Poland, 87-100

Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu Szpital Obserwacyjno-Zakazny

Torun, Poland, 87-100

Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu

Torun, Poland, 87-100

Wojewodzki Szpital Zespolony im. L. Rydygiera, Szpital Specjalistyczny dla Dzieci I Doroslych

Torun, Poland, 87-100

Portugal

Instituto Português de Oncologia de Coimbra Francisco Gentil, EPE

Coimbra, Portugal, 3000-075

Hospital Da Luz Coimbra, SA

Coimbra, Portugal, 3020-479

Centro Hospitalar de Lisboa Central, E.P.E. - Hospital de Santo António dos Capuchos

Lisboa, Portugal, 1169-050

Hospital CUF Descobertas, SA

Lisboa, Portugal, 1998-018

Dr. Campos Costa - Consultório de Tomografia Computorizada, S.A.

Porto, Portugal, 4050-075

Instituto Português de Oncologia do Porto Francisco Gentil, EPE

Porto, Portugal, 4200-072

Centro Hospitalar de São João, EPE

Porto, Portugal, 4200-319

Dr. Campos Costa - Consultório de Tomografia Computorizada, S.A.- Matosinhos

Senhora da Hora, Portugal, 4460-188

Centro Hospitalar de Trás-os-Montes e Alto Douro, EPE

Vila Real, Portugal, 5000-508

Russian Federation

State Budgetary Healthcare Insti. Republican Clinical Oncology Dispensary of the MoH of Bashk. Rep.

Ufa, Bashkortostan Republic, Russian Federation, 450054

Federal State Budgetary Institution "National medical research radiology center" MoH RF

Obninsk, Kaluzhskaya Region, Russian Federation, 249036

Private Medical Institution "Evromedservice"

Pushkin, Saint Petersburg, Russian Federation, 196603

Principal Military Clinical Hospital n.a. N.N. Burdenko

Moscow, Russian Federation, 105229

Moscow Research Oncology Institute named after P. A. Gertsen

Moscow, Russian Federation, 125284

BHI of Omsk region "Clinical oncological dispensary"

Omsk, Russian Federation, 644013

FGBIH "Clinical Hospital #122 n.a. L.G. Sokolov of Federal Medico-biological agency"

St. Petersburg, Russian Federation, 194291

Non-State Healthcare Institution "Railway Clinical Hospital JSC RZhD"

St. Petersburg, Russian Federation, 195271

FSBEI HE "First St. Petersburg State Medical University n. a. academician l.P Pavlov" MoH RF

St. Petersburg, Russian Federation, 197022

FSBEI HE "First St. Petersburg State Medical University n.a. academician I.P Pavlov" MoH RF

St. Petersburg, Russian Federation, 197022

FSBEI HE "First St. Petersburg State Medical University n.a. academician I.P Pavlov"

St. Petersburg, Russian Federation, 197022

"Ramsay Diagnostics Rus", LLC

St. Petersburg, Russian Federation, 197046

FSBI "Russian Scientific Center For Radiology and Surgical Technologies n.a. Academician A.M. Granov

St. Petersburg, Russian Federation, 197758

Hospital Orkli, LLC

St. Petersburg, Russian Federation, 199178

Mart, Llc

St. Petersburg, Russian Federation, 199178

SHI YR "Regional Clinical Oncology Hospital"

Yaroslavl, Russian Federation, 150054

Serbia

Institute for Oncology and Radiology of Serbia

Belgrade, Serbia, 11000

Clinical Centre Nis, Clinic of Oncology

Nis, Serbia, 18000

Oncology Institute of Vojvodina

Sremska Kamenica, Serbia, 21204

Spain

C.H. Univ. Santiago de Compostela

Santiago de Compostela, A Coruña, Spain, 15706

Hospital Comarcal General de Elda de Virgen de la Salud

Elda, Alicante, Spain, 03600

Hospital Universitario Central de Asturias

Oviedo, Asturias, Spain, 33011

Hospital Universitario Germans Trias i Pujol

Badalona, Barcelona, Spain, 08916

Institut Catalá d'Oncología - Hospital Duran i Reynals

l´Hospitalet de LLobregat, Barcelona, Spain, 08908

Institut Catalá d'Oncología

L´Hospitalet de Llobregat, Barcelona, Spain, 08908

Althaia. Xarxa Assistencial Universitaria de Manresa

Manresa, Barcelona, Spain, 08243

Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, Spain, 08208

Hospital General Universitario de Elche

Elche, Comunidad Valenciana, Spain, 03203

Hospital Clinico Universitario de Valencia

Valencia, Comunidad Valenciana, Spain, 46010

C. H. Universitario de Vigo- Hospital Álvaro Cunqueiro

Vigo, Galicia, Spain, 31008

C. H. Universitario de Vigo- Hospital Álvaro Cunqueiro

Vigo, Galicia, Spain, 36312

C.H. Universitario de Vigo- Hospital Meixoeiro

Vigo, Galicia, Spain, 36313

Hospital Universitario Infanta Sofia

San Sebastian de los Reyes, Madrid, Spain, 28702

Hospital Universitario Infanta Sofia

San Sebastián de los Reyes, Madrid, Spain, 28702

Clinica Universidad de Navarra

Pamplona, Navarra, Spain, 31008

Complejo Hospitalario de Navarra

Pamplona, Navarra, Spain, 31008

Hospital Vithas Internacional Medimar

Alicante, Spain, 03016

Hospital Universitario Infanta Cristina

Badajoz, Spain, 06080

Hospital del Mar

Barcelona, Spain, 08003

Hospital Quiron of Barcelona

Barcelona, Spain, 08023

Hospital Quiron

Barcelona, Spain, 08023

Hospital Quirón de Barcelona

Barcelona, Spain, 08023

Hospital de La Santa Creu i Sant pau_Oncology department

Barcelona, Spain, 08025

Hospital de La Santa Creu i Sant Pau

Barcelona, Spain, 08025

CETIR Grup Medic

Barcelona, Spain, 08029

Cetir, Centre Mèdic, S.L

Barcelona, Spain, 08029

Hospital de Vall d'Hebron

Barcelona, Spain, 08035

Hospital Universitario Vall d'Hebron

Barcelona, Spain, 08035

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

Laboratorio Dr. F. Echevarne Analisis, S.A

Barcelona, Spain, 08037

Hospital Universitario Reina Sofia

Cordoba, Spain, 14004

Hospital Universitario Reina Sofía

Cordoba, Spain, 14004

H. univ Girona Dr. Josep Trueta - lnstitut Catala d'Oncologia

Gerona, Spain, 17007

Institut Catala d'Oncologia

Gerona, Spain, 17007

Institut Diagnostic de la lmatge

Gerona, Spain, 17007

Hospital Universitario Lucus Augusti

Lugo, Spain, 27003

Fundacion Maria Rafols para la investigacion del Diagnostico de la imagen

Madrid, Spain, 28006

Gabinete Radiologico Doctor Pita

Madrid, Spain, 28006

Hospital General Universitario Gregorio Marañon

Madrid, Spain, 28007

Hospital Ruber Internacional

Madrid, Spain, 28034

Hospital Ruber International

Madrid, Spain, 28034

Hospital Universitario Ramón y Cajal

Madrid, Spain, 28034

Hospital Clinico San Carlos

Madrid, Spain, 28040

Hospital Clínico San Carlos

Madrid, Spain, 28040

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Hospital Universitario La Paz

Madrid, Spain, 28046

Hospital Universitario HM Sanchinarro - CIOCC

Madrid, Spain, 28050

Hospital Universitario Virgen del Rocio

Sevilla, Spain, 41013

Instituto Valenciano de Oncología

Valencia, Spain, 46009

Hospital Clínico Universitario de Valencia

Valencia, Spain, 46010

Hospital Clinico Universitario de Valencia

Valencia, Spain, 4610

Sweden

APL

Stockholm, Sweden, 171 64

Karolinska University Hospital

Stockholm, Sweden, 171 76

Taiwan

Clinical Trial Pharmacy, China Medical University Hospital

Taichung, Taiwan, 40447

China Medical University Hospital

Taichung, Taiwan, 404

Department of Pharmacy, National Cheng Kung University Hospital

Tainan, Taiwan, 704

National Cheng Kung University Hospital

Tainan, Taiwan, 704

Investigational Drug services, National Taiwan University Hospital

Taipei, Taiwan, 100

National Taiwan University Hospital

Taipei, Taiwan, 100

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, Taiwan, 112

Pharmacy, Koo Foundation Sun Yat-Sen Cancer Center

Taipei, Taiwan, 112

Chang Gung Memorial Hospital, Linkou

Taoyuan, Taiwan, 333

Chemotherapy pharmacy, Chang Gung Memorial Hospital, Linkou

Taoyuan, Taiwan, 333

United Kingdom

Royal United Hospitals Bath NHS Foundation Trust

Bath, United Kingdom, BA1 3NG

St Bartholomew 's Hospital, Barts Health NHS Trust

London, United Kingdom, EC1A 7BE

St. Bartholomew's Hospital, Barts Health NHS Trust

London, United Kingdom, EC1A 7BE

Guy's & St. Thomas' NHS Foundation Trust

London, United Kingdom, SE1 9RT

Guy's and St Thomas' NHS Foundation Trust, Guy's Hospital

London, United Kingdom, SE1 9RT

Churchill Hospital, Oxford University Hospitals NHS Trust

Oxford, United Kingdom, OX3 7LE

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

  Study Documents (Full-Text)

Documents provided by Pfizer:

Study Protocol  [PDF] March 8, 2021

Statistical Analysis Plan  [PDF] April 2, 2019

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte RJ, Huang B, Costa N, Blake-Haskins JA, Grivas P. Plain language summary of results from the JAVELIN Bladder 100 study: avelumab maintenance treatment for advanced urothelial cancer. Future Oncol. 2022 Jun;18(19):2361-2371. doi: 10.2217/fon-2021-1631. Epub 2022 Apr 13.

Tomita Y, Yamamoto Y, Tsuchiya N, Kanayama H, Eto M, Miyake H, Powles T, Yoshida M, Koide Y, Umeyama Y, di Pietro A, Uemura H. Avelumab first-line maintenance plus best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma: JAVELIN Bladder 100 Japanese subgroup analysis. Int J Clin Oncol. 2022 Feb;27(2):383-395. doi: 10.1007/s10147-021-02067-8. Epub 2022 Jan 1.

Powles T, Sridhar SS, Loriot Y, Bellmunt J, Mu XJ, Ching KA, Pu J, Sternberg CN, Petrylak DP, Tambaro R, Dourthe LM, Alvarez-Fernandez C, Aarts M, di Pietro A, Grivas P, Davis CB. Avelumab maintenance in advanced urothelial carcinoma: biomarker analysis of the phase 3 JAVELIN Bladder 100 trial. Nat Med. 2021 Dec;27(12):2200-2211. doi: 10.1038/s41591-021-01579-0. Epub 2021 Dec 10.

Powles T, Park SH, Voog E, Caserta C, Valderrama BP, Gurney H, Kalofonos H, Radulovic S, Demey W, Ullen A, Loriot Y, Sridhar SS, Tsuchiya N, Kopyltsov E, Sternberg CN, Bellmunt J, Aragon-Ching JB, Petrylak DP, Laliberte R, Wang J, Huang B, Davis C, Fowst C, Costa N, Blake-Haskins JA, di Pietro A, Grivas P. Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2020 Sep 24;383(13):1218-1230. doi: 10.1056/NEJMoa2002788. Epub 2020 Sep 18.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02603432
• Other Study ID Numbers: B9991001; 2015-003262-86 ( EudraCT Number ); JAVELIN BLADDER 100 ( Other Identifier: Alias Study Number )
• First Posted: November 11, 2015
• Results First Posted: December 17, 2020
• Last Update Posted: March 27, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pfizer:

Bladder cancer; Urologic neoplasms; urothelial carcinoma; PD-L1; programmed cell death protein; maintenance treatment

Additional relevant MeSH terms:

Avelumab; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs