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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02453282




Registration number
NCT02453282
Ethics application status
Date submitted
20/05/2015
Date registered
25/05/2015

Titles & IDs
Public title
Phase III Open Label First Line Therapy Study of MEDI 4736 (Durvalumab) With or Without Tremelimumab Versus SOC in Non Small-Cell Lung Cancer (NSCLC)
Scientific title
A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy or MEDI4736 Monotherapy Versus Standard of Care Platinum-Based Chemotherapy in First Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Cancer (NSCLC)(MYSTIC).
Secondary ID [1] 0 0
2015-001279-39
Secondary ID [2] 0 0
D419AC00001
Universal Trial Number (UTN)
Trial acronym
MYSTIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small-Cell Lung Carcinoma NSCLC 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Paclitaxel + Carboplatin
Treatment: Drugs - Gemcitabine + Cisplatin
Treatment: Drugs - Gemcitabine + Carboplatin
Treatment: Drugs - Pemetrexed + Cisplatin
Treatment: Drugs - Pemetrexed + Carboplatin

Experimental: Monotherapy - PD-L1 monoclonal Antibody monotherapy.

Experimental: Combination Therapy - PD-L1+Tremelimumab combination therapy

Active comparator: Standard of Care - Standard of Care chemotherapy treatment


Treatment: Drugs: Paclitaxel + Carboplatin
Chemotherapy Agents

Treatment: Drugs: Gemcitabine + Cisplatin
Chemotherapy Agents

Treatment: Drugs: Gemcitabine + Carboplatin
Chemotherapy Agents

Treatment: Drugs: Pemetrexed + Cisplatin
Chemotherapy Agents

Treatment: Drugs: Pemetrexed + Carboplatin
Chemotherapy Agents

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy
Timepoint [1] 0 0
From baseline (Day 1, Week 0) until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Primary outcome [2] 0 0
Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy
Timepoint [2] 0 0
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [1] 0 0
OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy
Timepoint [1] 0 0
From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [2] 0 0
OS; PD-L1 (TC >=1%) Analysis Set Population
Timepoint [2] 0 0
From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [3] 0 0
OS; FAS Population
Timepoint [3] 0 0
From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [4] 0 0
PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy
Timepoint [4] 0 0
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [5] 0 0
PFS; PD-L1 (TC >=1%) Analysis Set Population
Timepoint [5] 0 0
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [6] 0 0
PFS; FAS Population
Timepoint [6] 0 0
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [7] 0 0
Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population
Timepoint [7] 0 0
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [8] 0 0
ORR; PD-L1 (TC >=1%) Analysis Set Population
Timepoint [8] 0 0
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [9] 0 0
ORR; FAS Population
Timepoint [9] 0 0
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [10] 0 0
Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population
Timepoint [10] 0 0
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [11] 0 0
DoR; PD-L1 (TC >=1%) Analysis Set Population
Timepoint [11] 0 0
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [12] 0 0
DoR; FAS Population
Timepoint [12] 0 0
Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).
Secondary outcome [13] 0 0
Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population
Timepoint [13] 0 0
Tumour scans performed at baseline then every 6 weeks up to 12 months.
Secondary outcome [14] 0 0
Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population
Timepoint [14] 0 0
Tumour scans performed at baseline then every 6 weeks up to 12 months.
Secondary outcome [15] 0 0
Percentage of Participants APF12; FAS Population
Timepoint [15] 0 0
Tumour scans performed at baseline then every 6 weeks up to 12 months.
Secondary outcome [16] 0 0
Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population
Timepoint [16] 0 0
Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
Secondary outcome [17] 0 0
PFS2; PD-L1 (TC >=1%) Analysis Set Population
Timepoint [17] 0 0
Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
Secondary outcome [18] 0 0
PFS2; FAS Population
Timepoint [18] 0 0
Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).
Secondary outcome [19] 0 0
Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months
Timepoint [19] 0 0
At baseline then every 4 weeks for the first 8 weeks relative to the date of randomization, then every 8 weeks until second progression/death, whichever comes first. Assessed up to 12 months.
Secondary outcome [20] 0 0
Serum Concentrations of Durvalumab
Timepoint [20] 0 0
Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, and at follow-up Month 3.
Secondary outcome [21] 0 0
Serum Concentrations of Tremelimumab
Timepoint [21] 0 0
Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3.
Secondary outcome [22] 0 0
Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab
Timepoint [22] 0 0
Within 1 hour after end of infusion on infusion day at Week 12.
Secondary outcome [23] 0 0
Cmax_ss of Tremelimumab
Timepoint [23] 0 0
Within 1 hour after end of infusion on infusion day at Week 12.
Secondary outcome [24] 0 0
Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab
Timepoint [24] 0 0
Pre-dose at Week 12.
Secondary outcome [25] 0 0
Ctrough_ss of Tremelimumab
Timepoint [25] 0 0
Pre-dose at Week 12.
Secondary outcome [26] 0 0
Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab
Timepoint [26] 0 0
At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment.
Secondary outcome [27] 0 0
Number of Participants With ADA Response to Tremelimumab
Timepoint [27] 0 0
At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.

Eligibility
Key inclusion criteria
For inclusion in the study, patients should fulfill the following criteria:

* Aged at least 18 years
* Documented evidence of Stage IV NSCLC
* No sensitizing EGFR mutation or ALK rearrangement
* No prior chemotherapy or any other systemic therapy for recurrent/metastatic NSCLC
* World Health Organization (WHO) Performance Status of 0 or 1
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients should not enter the study if any of the following exclusion criteria are fulfilled:

1. Mixed small-cell lung cancer and NSCLC histology, sarcomatoid variant
2. Brain metastases or spinal cord compression unless asymptomatic, treated and stable (not requiring steroids)
3. Prior exposure to Immunomodulatory therapy (IMT), including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), anti-programmed cell death1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies, excluding therapeutic anticancer vaccines
4. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease]

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Box Hill
Recruitment hospital [2] 0 0
Research Site - Gosford
Recruitment hospital [3] 0 0
Research Site - Kogarah
Recruitment hospital [4] 0 0
Research Site - Melbourne
Recruitment hospital [5] 0 0
Research Site - Port Macquarie
Recruitment hospital [6] 0 0
Research Site - Southport
Recruitment hospital [7] 0 0
Research Site - St Leonards
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
2250 - Gosford
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
3000 - Melbourne
Recruitment postcode(s) [5] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [6] 0 0
4215 - Southport
Recruitment postcode(s) [7] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Hawaii
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Minnesota
Country [9] 0 0
United States of America
State/province [9] 0 0
Missouri
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Virginia
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United States of America
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Wisconsin
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Belgium
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Brussels
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Belgium
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Charleroi
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Belgium
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Duffel
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Belgium
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Leuven
Country [23] 0 0
Belgium
State/province [23] 0 0
Liège
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Canada
State/province [24] 0 0
Ontario
Country [25] 0 0
Canada
State/province [25] 0 0
Saskatchewan
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France
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Bordeaux Cedex
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France
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Brest Cedex
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France
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Creteil
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France
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Lille
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France
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Lyon Cedex 08
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France
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Marseille cedex
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Germany
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Aachen
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Germany
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Bad Berka
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Germany
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Berlin
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Germany
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Freiburg
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Germany
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Gauting
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Germany
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Hamburg
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Germany
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Heidelberg
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Germany
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Hemer
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Germany
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Homburg/Saar
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Germany
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Immenhausen
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Germany
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Lubeck
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Germany
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Löwenstein
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Germany
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Mainz
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Germany
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Münster
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Germany
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Oldenburg
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Germany
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Ulm
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Germany
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Velbert
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Germany
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Würzburg
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Hungary
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Budapest
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Hungary
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Deszk
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Hungary
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Edelény
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Hungary
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Kaposvár
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Hungary
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Kecskemét
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Hungary
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Miskolc
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Hungary
State/province [56] 0 0
Nyíregyháza
Country [57] 0 0
Hungary
State/province [57] 0 0
Pécs
Country [58] 0 0
Hungary
State/province [58] 0 0
Székesfehérvár
Country [59] 0 0
Italy
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Genova
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Italy
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Meldola
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Italy
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Milano
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Italy
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San Giovanni Rotondo
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Italy
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Siena
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Japan
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Fukushima-shi
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Japan
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Himeji-shi
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Japan
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Hirakata-shi
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Japan
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Hirosaki-shi
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Japan
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Iizuka-shi
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Japan
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Iwakuni-shi
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Japan
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Izumi-shi
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Japan
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Kanazawa
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Japan
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Kishiwada-shi
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Japan
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Kobe-shi
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Japan
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Koga-shi
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Japan
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Kyoto-shi
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Japan
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Mitaka-shi
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Japan
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Nagaoka-shi
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Japan
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Nagoya-shi
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Japan
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Okayama-shi
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Japan
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Osaka-shi
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Japan
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Osakasayama
Country [82] 0 0
Japan
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Saga-shi
Country [83] 0 0
Japan
State/province [83] 0 0
Saitama-shi
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Japan
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Sakai-shi
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Japan
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Sendai-shi
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Japan
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Shinjuku-ku
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Japan
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Tokushima-shi
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Japan
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Ube-shi
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Japan
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Yokohama-shi
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Japan
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Yokosuka-shi
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Korea, Republic of
State/province [91] 0 0
Busan
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Korea, Republic of
State/province [92] 0 0
Changwon-si
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Korea, Republic of
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Cheongju-si
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Korea, Republic of
State/province [94] 0 0
Daegu
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Korea, Republic of
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Daejeon
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Korea, Republic of
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Goyang-si
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Korea, Republic of
State/province [97] 0 0
Incheon
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Korea, Republic of
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Jinju-si
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Korea, Republic of
State/province [99] 0 0
Seongnam-si
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Korea, Republic of
State/province [100] 0 0
Seongnam-Si
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Korea, Republic of
State/province [101] 0 0
Seoul
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Korea, Republic of
State/province [102] 0 0
Suwon-si
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Korea, Republic of
State/province [103] 0 0
Ulsan
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Netherlands
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Amsterdam
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Netherlands
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Arnhem
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Netherlands
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Breda
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Netherlands
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Den Bosch
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Netherlands
State/province [108] 0 0
Groningen
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Netherlands
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Maastricht
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Netherlands
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Rotterdam
Country [111] 0 0
Russian Federation
State/province [111] 0 0
Moscow
Country [112] 0 0
Russian Federation
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Obninsk
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Russian Federation
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Omsk
Country [114] 0 0
Russian Federation
State/province [114] 0 0
Saint Petersburg
Country [115] 0 0
Russian Federation
State/province [115] 0 0
Saint-Petersburg
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Russian Federation
State/province [116] 0 0
St. Petersburg
Country [117] 0 0
Spain
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A Coruña
Country [118] 0 0
Spain
State/province [118] 0 0
Alicante
Country [119] 0 0
Spain
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Barcelona
Country [120] 0 0
Spain
State/province [120] 0 0
Gerona
Country [121] 0 0
Spain
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Jaén
Country [122] 0 0
Spain
State/province [122] 0 0
León
Country [123] 0 0
Spain
State/province [123] 0 0
Madrid
Country [124] 0 0
Spain
State/province [124] 0 0
Majadahonda
Country [125] 0 0
Spain
State/province [125] 0 0
Málaga
Country [126] 0 0
Spain
State/province [126] 0 0
Sevilla
Country [127] 0 0
Spain
State/province [127] 0 0
Valencia
Country [128] 0 0
Switzerland
State/province [128] 0 0
Bellinzona
Country [129] 0 0
Switzerland
State/province [129] 0 0
Lausanne
Country [130] 0 0
Taiwan
State/province [130] 0 0
Kaohsiung
Country [131] 0 0
Taiwan
State/province [131] 0 0
Taichung
Country [132] 0 0
Taiwan
State/province [132] 0 0
Tainan City
Country [133] 0 0
Taiwan
State/province [133] 0 0
Taipei
Country [134] 0 0
Taiwan
State/province [134] 0 0
Tao-Yuan
Country [135] 0 0
Thailand
State/province [135] 0 0
Bangkok
Country [136] 0 0
Thailand
State/province [136] 0 0
Chiang Mai
Country [137] 0 0
Thailand
State/province [137] 0 0
Hat Yai
Country [138] 0 0
Thailand
State/province [138] 0 0
Khon Kaen
Country [139] 0 0
Vietnam
State/province [139] 0 0
Hanoi City
Country [140] 0 0
Vietnam
State/province [140] 0 0
Hanoi
Country [141] 0 0
Vietnam
State/province [141] 0 0
Ho Chi Minh city
Country [142] 0 0
Vietnam
State/province [142] 0 0
Ho Chi Minh

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Stuart McIntosh, MD
Address 0 0
AstraZeneca, Alderley Park, Cheshire, UK
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.