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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00069095




Registration number
NCT00069095
Ethics application status
Date submitted
15/09/2003
Date registered
18/09/2003
Date last updated
6/10/2016

Titles & IDs
Public title
A Study of Capecitabine (Xeloda) and Bevacizumab as a First-line Therapy in Patients With Metastatic Colorectal Cancer
Scientific title
A 2x2 Factorial Randomized Phase III Study of Intermittent Oral Capecitabine in Combination With Intravenous Oxaliplatin (Q3W) ("XELOX") With/Without Intravenous Bevacizumab (Q3W) Versus Bolus and Continuous Infusion Fluorouracil/Intravenous Leucovorin With Intravenous Oxaliplatin (Q2W) ("FOLFOX-4") With/Without Intravenous Bevacizumab (Q2W) as First-line Treatment for Patients With Metastatic Colorectal Cancer
Secondary ID [1] 0 0
NO16966
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Oxaliplatin 130 mg/m^2
Treatment: Drugs - Capecitabine 1000 mg/m^2
Treatment: Drugs - Bevacizumab 7.5 mg/kg
Treatment: Drugs - Placebo for bevacizumab 7.5 mg/kg
Treatment: Drugs - Oxaliplatin 85 mg/m^2
Treatment: Drugs - Leucovorin 200 mg/m^2
Treatment: Drugs - Bevacizumab 5 mg/kg
Treatment: Drugs - Placebo for bevacizumab 5 mg/kg

Experimental: XELOX (oxaliplatin+capecitabine) - Patients in the 2-arm part of the study received oxaliplatin 130 mg/m\^2 intravenously (iv) on Day 1 of every 3 week cycle + capecitabine 1000 mg/m\^2 orally twice a day for the first 2 weeks of every 3 week cycle. Patients in the 4-arm part of the study received the same treatments plus placebo for bevacizumab 7.5 mg/kg iv on Day 1 of every 3 week cycle.

Experimental: XELOX (oxaliplatin+capecitabine) + bevacizumab - Patients in the 4-arm part of the study received oxaliplatin 130 mg/m\^2 intravenously (iv) on Day 1 of every 3 week cycle + capecitabine 1000 mg/m\^2 orally twice a day for the first 2 weeks of every 3 week cycle + bevacizumab 7.5 mg/kg iv on Day 1 of every 3 week cycle.

Active comparator: FOLFOX-4 (oxaliplatin+leucovorin+fluorouracil) - Patients in the 2-arm part of the study received oxaliplatin 85 mg/m\^2 intravenously (iv) + leucovorin 200 mg/m\^2 iv on Day 1 of every 2 week cycle + fluorouracil 400 mg/m\^2 bolus injection over 2 to 4 min followed by 600 mg/m\^2 continuous infusion over 22 h on Days 1 and 2 of every 2 week cycle. Patients in the 4-arm part of the study received the same treatments plus placebo for bevacizumab 5 mg/kg iv on Day 1 of every 2 week cycle.

Active comparator: FOLFOX-4 (oxaliplatin+leucovorin+fluorouracil) + bevacizumab - Patients in the 4-arm part of the study received oxaliplatin 85 mg/m\^2 intravenously (iv) + leucovorin 200 mg/m\^2 iv + bevacizumab 5 mg/kg iv on Day 1 of every 2 week cycle + fluorouracil 400 mg/m\^2 bolus injection over 2 to 4 min followed by 600 mg/m\^2 continuous infusion over 22 h on Days 1 and 2 of every 2 week cycle.


Treatment: Drugs: Oxaliplatin 130 mg/m^2
Oxaliplatin was administered in a 2 h infusion before the first dose of capecitabine.

Treatment: Drugs: Capecitabine 1000 mg/m^2
Capecitabine was taken within 30 min after the end of breakfast and dinner.

Treatment: Drugs: Bevacizumab 7.5 mg/kg
Bevacizumab was administered in a 30 to 90 min infusion.

Treatment: Drugs: Placebo for bevacizumab 7.5 mg/kg
Placebo control for bevacizumab (volume equivalent to 7.5 mg/kg bevacizumab) was administered in a 30 to 90 min infusion.

Treatment: Drugs: Oxaliplatin 85 mg/m^2
Oxaliplatin 85 mg/m\^2 was administered simultaneously with leucovorin in a 2 h infusion.

Treatment: Drugs: Leucovorin 200 mg/m^2
Leucovorin was administered simultaneously with oxaliplatin 85 mg/m\^2 in a 2 h infusion.

Treatment: Drugs: Bevacizumab 5 mg/kg
Bevacizumab was administered in a 30 to 90 min infusion.

Treatment: Drugs: Placebo for bevacizumab 5 mg/kg
Placebo control for bevacizumab (volume equivalent to 5 mg/kg bevacizumab) was administered in a 30 to 90 min infusion.

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

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) by General Approach (Participants With Curative Surgery Censored): Non-inferiority of XELOX Versus FOLFOX-4
Timepoint [1] 0 0
Baseline until disease progression or death, approximately 2 years 6 months
Primary outcome [2] 0 0
PFS as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) by General Approach (Participants With Curative Surgery Censored) - Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Timepoint [2] 0 0
Baseline until disease progression or death, approximately 2 years 6 months
Secondary outcome [1] 0 0
PFS as Assessed by the Independent Review Committee (IRC) (General Approach, Participants With Curative Surgery Censored) - Non-inferiority of XELOX Versus FOLFOX-4
Timepoint [1] 0 0
Baseline until disease progression or death, approximately 2 years 6 months
Secondary outcome [2] 0 0
PFS as Assessed by the Independent Review Committee (IRC) (General Approach, Participants With Curative Surgery Censored) - Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Timepoint [2] 0 0
Baseline until disease progression or death, approximately 2 years 6 months
Secondary outcome [3] 0 0
PFS (On-treatment Approach): Non-inferiority of XELOX Versus FOLFOX-4
Timepoint [3] 0 0
Baseline until disease progression or death, approximately 2 years 6 months
Secondary outcome [4] 0 0
PFS (On-treatment Approach): Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Timepoint [4] 0 0
Baseline until disease progression or death, approximately 2 years 6 months
Secondary outcome [5] 0 0
PFS by General Approach, Participants With Curative Surgery Not Censored: Non-inferiority of XELOX Versus FOLFOX-4
Timepoint [5] 0 0
Baseline until disease progression or death, approximately 2 years 6 months
Secondary outcome [6] 0 0
PFS by General Approach, Participants With Curative Surgery Not Censored: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Timepoint [6] 0 0
Baseline until disease progression or death, approximately 2 years 6 months
Secondary outcome [7] 0 0
Overall Survival: Non-inferiority of XELOX Versus FOLFOX-4
Timepoint [7] 0 0
Baseline until disease progression or death, approximately 2 years 6 months
Secondary outcome [8] 0 0
Overall Survival: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Timepoint [8] 0 0
Baseline until disease progression or death, approximately 2 years 6 months
Secondary outcome [9] 0 0
Best Overall Response (BOR) as Assessed by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST): Non-inferiority of XELOX Versus FOLFOX-4
Timepoint [9] 0 0
From baseline until disease progression/recurrence, approximately 2 years 6 months
Secondary outcome [10] 0 0
Best Overall Response (BOR) as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Timepoint [10] 0 0
From baseline until disease progression/recurrence, approximately 2 years 6 months
Secondary outcome [11] 0 0
BOR as Assessed by the IRC According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
Timepoint [11] 0 0
From baseline until disease progression/recurrence, approximately 2 years 6 months
Secondary outcome [12] 0 0
BOR as Assessed by the IRC According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Timepoint [12] 0 0
From baseline until disease progression/recurrence, approximately 2 years 6 months
Secondary outcome [13] 0 0
Time to Treatment Failure (TTF) as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
Timepoint [13] 0 0
From baseline until disease progression/recurrence, approximately 2 years 6 months
Secondary outcome [14] 0 0
Time to Treatment Failure as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Timepoint [14] 0 0
From baseline until disease progression/recurrence, approximately 2 years 6 months
Secondary outcome [15] 0 0
Time to Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
Timepoint [15] 0 0
Week 1 to Week 54
Secondary outcome [16] 0 0
Time to Response as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Timepoint [16] 0 0
Week 1 to Week 54
Secondary outcome [17] 0 0
Duration of Overall Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
Timepoint [17] 0 0
From baseline until disease progression/recurrence, approximately 2 years 6 months
Secondary outcome [18] 0 0
Duration of Overall Response as Assessed by the Investigator According to RECIST: Superiority Analysis of Chemotherapy Plus Bevacizumab Versus Chemotherapy Alone
Timepoint [18] 0 0
From baseline until disease progression/recurrence, approximately 2 years 6 months
Secondary outcome [19] 0 0
Duration of Complete Response as Assessed by the Investigator According to RECIST: Non-inferiority of XELOX Versus FOLFOX-4
Timepoint [19] 0 0
From baseline until disease progression/recurrence, approximately 2 years 6 months
Secondary outcome [20] 0 0
Duration of Complete Response as Assessed by the Investigator According to RECIST: Superiority of Chemotherapy Plus BV Over Chemotherapy Alone
Timepoint [20] 0 0
From baseline until disease progression/recurrence, approximately 2 years 6 months

Eligibility
Key inclusion criteria
* Adult patients = 18 years of age.
* Metastatic colorectal cancer.
* = 1 target lesion.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous treatment with oxaliplatin or bevacizumab.
* Previous systemic chemotherapy or immunotherapy for advanced or metastatic disease.
* Progressive disease during or within 6 months of completion of previous adjuvant therapy.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
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
- Adelaide
Recruitment hospital [2] 0 0
- Box Hill
Recruitment hospital [3] 0 0
- Brisbane
Recruitment hospital [4] 0 0
- Camperdown
Recruitment hospital [5] 0 0
- Fitzroy
Recruitment hospital [6] 0 0
- Footscray
Recruitment hospital [7] 0 0
- Kurralta Park
Recruitment hospital [8] 0 0
- Malvern
Recruitment hospital [9] 0 0
- Melbourne
Recruitment hospital [10] 0 0
- Perth
Recruitment hospital [11] 0 0
- Port Macquarie
Recruitment hospital [12] 0 0
- St. Leonards
Recruitment hospital [13] 0 0
- Sydney
Recruitment postcode(s) [1] 0 0
5011 - Adelaide
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
4101 - Brisbane
Recruitment postcode(s) [4] 0 0
2050 - Camperdown
Recruitment postcode(s) [5] 0 0
3065 - Fitzroy
Recruitment postcode(s) [6] 0 0
3011 - Footscray
Recruitment postcode(s) [7] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [8] 0 0
3144 - Malvern
Recruitment postcode(s) [9] 0 0
3002 - Melbourne
Recruitment postcode(s) [10] 0 0
3181 - Melbourne
Recruitment postcode(s) [11] 0 0
6000 - Perth
Recruitment postcode(s) [12] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [13] 0 0
2065 - St. Leonards
Recruitment postcode(s) [14] 0 0
2031 - Sydney
Recruitment postcode(s) [15] 0 0
2139 - Sydney
Recruitment outside Australia
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United States of America
State/province [1] 0 0
California
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United States of America
State/province [2] 0 0
Connecticut
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United States of America
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Florida
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United States of America
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Georgia
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United States of America
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Illinois
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United States of America
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Kentucky
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United States of America
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Louisiana
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Maine
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Massachusetts
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Michigan
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Minnesota
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Nevada
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United States of America
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New Jersey
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United States of America
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New Mexico
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United States of America
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New York
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North Carolina
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North Dakota
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United States of America
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Pennsylvania
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United States of America
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Rhode Island
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Vermont
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Virginia
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Austria
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Wels
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Wien
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Brazil
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Rio de Janeiro
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Alberta
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Manitoba
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Colmar
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Mainz
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Mannheim
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Regensburg
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Stralsund
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Trier
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Gyor
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Israel
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Israel
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Israel
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Israel
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Ancona
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Italy
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Genova
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Italy
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Modena
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Italy
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Padova
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Italy
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Parma
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Italy
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Pavia
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Italy
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Reggio Emilia
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Italy
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Sassari
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Korea, Republic of
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Seoul
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Mexico
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Mexico City
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New Zealand
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Bergen
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Oslo
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Tromsø
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Russian Federation
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Moscow
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Russian Federation
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Pretoria
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Sandton
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Barcelona
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Spain
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Leganes
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Spain
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Madrid
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Málaga
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Santander
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Spain
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Valencia
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Spain
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Zaragoza
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Sweden
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Gaevle
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Sweden
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Karlstad
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Sweden
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Stockholm
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Sweden
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Uppsala
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Sweden
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Västerås
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Switzerland
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Bern
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Switzerland
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Geneve
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Taiwan
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Kueishan
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Taiwan
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Taipei
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Thailand
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Bangkok
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Thailand
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Khon Kaen
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Turkey
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Istanbul
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Turkey
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Izmir
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United Kingdom
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Aberdeen
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United Kingdom
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Birmingham
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United Kingdom
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Cardiff
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United Kingdom
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Derby
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United Kingdom
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Glasgow
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United Kingdom
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Guildford
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United Kingdom
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Hull
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United Kingdom
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London
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United Kingdom
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Maidstone
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United Kingdom
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Newcastle Upon Tyne
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United Kingdom
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Northwood
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United Kingdom
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Nottingham
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United Kingdom
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Plymouth
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United Kingdom
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Salisbury
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United Kingdom
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Southampton
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United Kingdom
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Sutton
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United Kingdom
State/province [157] 0 0
Taunton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.