A Study of Capecitabine (Xeloda) and Bevacizumab as a First-line Therapy in Patients With Metastatic Colorectal Cancer

NCT ID: NCT00069095

Last Updated: 2016-10-06

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2035 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-07-31

Study Completion Date

2009-04-30

Brief Summary

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This 4 arm study assessed the efficacy and safety of oral capecitabine (Xeloda) or intravenous (iv) fluorouracil/leucovorin, in combination with iv oxaliplatin (Eloxatin) with or without iv bevacizumab (Avastin), as a first-line treatment in patients with metastatic colorectal cancer. Patients were randomized to receive 1) XELOX (Xeloda 1000 mg/m\^2 orally \[po\] twice a day \[bid\] on Days 1-15 + oxaliplatin in 3 week cycles), 2) FOLFOX-4 (oxaliplatin + leucovorin + fluorouracil \[5-FU\] in 2 week cycles), 3) XELOX + bevacizumab (7.5 mg iv on Day 1 in 3 week cycles), or 4) FOLFOX-4 + bevacizumab (5 mg iv on Day 1 in 2 week cycles).

Detailed Description

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This study was conducted in 2 parts: An initial 2-arm part in which patients were randomized to 1 of 2 different treatment groups (XELOX or FOLFOX-4), and a subsequent 2 x 2 factorial part, added to the study through a protocol amendment, in which additional patients were randomized into one of 4 different treatment groups (XELOX + placebo, FOLFOX-4 + placebo, XELOX + bevacizumab, or FOLFOX-4 + bevacizumab). Due to the comparison of the oral agent capecitabine with bolus and infused fluorouracil, the study was not blinded with respect to these 2 treatments. The study was double-blind with regard to the administration of bevacizumab, ie, there was a placebo control for bevacizumab in the second part of the study.

The study consisted of 3 phases, a Primary Study Treatment Phase, a Post-Study Treatment Phase, and a Follow-Up Phase.

Primary Study Treatment Phase

Patients were to receive up to 16 cycles (2-arm part of the study) or 24 cycles (4-arm part of the study) of treatment during the Primary Study Treatment Phase (48 weeks).

Post-Study Treatment Phase

Patients who completed the 48-week primary study treatment phase without progressive disease were eligible to enter the post-study treatment phase at the discretion of the investigator and the sponsor. Patients who entered this phase were to continue treatment on the same regimen to which they were initially randomized until either progression of disease was documented, unacceptable toxicity occurred, or the patient withdrew consent.

Follow-up Phase

Patients who terminated study treatment during the primary or post-study treatment phase were followed until disease progression or death.

Conditions

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Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

Oxaliplatin 130 mg/m^2

Intervention Type DRUG

Oxaliplatin was administered in a 2 h infusion before the first dose of capecitabine.

Capecitabine 1000 mg/m^2

Intervention Type DRUG

Capecitabine was taken within 30 min after the end of breakfast and dinner.

Placebo for bevacizumab 7.5 mg/kg

Intervention Type DRUG

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

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.

Group Type EXPERIMENTAL

Oxaliplatin 130 mg/m^2

Intervention Type DRUG

Oxaliplatin was administered in a 2 h infusion before the first dose of capecitabine.

Capecitabine 1000 mg/m^2

Intervention Type DRUG

Capecitabine was taken within 30 min after the end of breakfast and dinner.

Bevacizumab 7.5 mg/kg

Intervention Type DRUG

Bevacizumab was administered in a 30 to 90 min infusion.

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.

Group Type ACTIVE_COMPARATOR

Oxaliplatin 85 mg/m^2

Intervention Type DRUG

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

Leucovorin 200 mg/m^2

Intervention Type DRUG

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

Fluorouracil 400 mg/m^2

Intervention Type DRUG

Placebo for bevacizumab 5 mg/kg

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

Oxaliplatin 85 mg/m^2

Intervention Type DRUG

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

Leucovorin 200 mg/m^2

Intervention Type DRUG

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

Fluorouracil 400 mg/m^2

Intervention Type DRUG

Bevacizumab 5 mg/kg

Intervention Type DRUG

Bevacizumab was administered in a 30 to 90 min infusion.

Interventions

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Oxaliplatin 130 mg/m^2

Oxaliplatin was administered in a 2 h infusion before the first dose of capecitabine.

Intervention Type DRUG

Capecitabine 1000 mg/m^2

Capecitabine was taken within 30 min after the end of breakfast and dinner.

Intervention Type DRUG

Bevacizumab 7.5 mg/kg

Bevacizumab was administered in a 30 to 90 min infusion.

Intervention Type DRUG

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.

Intervention Type DRUG

Oxaliplatin 85 mg/m^2

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

Intervention Type DRUG

Leucovorin 200 mg/m^2

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

Intervention Type DRUG

Fluorouracil 400 mg/m^2

Intervention Type DRUG

Bevacizumab 5 mg/kg

Bevacizumab was administered in a 30 to 90 min infusion.

Intervention Type DRUG

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 Type DRUG

Other Intervention Names

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Eloxatin Xeloda Avastin Eloxatin Efudex Avastin

Eligibility Criteria

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Inclusion Criteria

* Adult patients ≥ 18 years of age.
* Metastatic colorectal cancer.
* ≥ 1 target lesion.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Berkeley, California, United States

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Fountain Valley, California, United States

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Fullerton, California, United States

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Gilroy, California, United States

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Greenbrae, California, United States

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Los Angeles, California, United States

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Orange, California, United States

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Palo Alto, California, United States

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San Diego, California, United States

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Norwich, Connecticut, United States

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Waterbury, Connecticut, United States

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Boca Raton, Florida, United States

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Gainesville, Florida, United States

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Jacksonville, Florida, United States

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New Port Richey, Florida, United States

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Tampa, Florida, United States

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Tampa, Florida, United States

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Atlanta, Georgia, United States

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Chicago, Illinois, United States

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Elk Grove Village, Illinois, United States

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Peoria, Illinois, United States

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Lexington, Kentucky, United States

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New Orleans, Louisiana, United States

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Scarborough, Maine, United States

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Boston, Massachusetts, United States

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Ann Arbor, Michigan, United States

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Saint Louis Park, Minnesota, United States

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Las Vegas, Nevada, United States

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East Orange, New Jersey, United States

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Hamilton, New Jersey, United States

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New Brunswick, New Jersey, United States

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Albuquerque, New Mexico, United States

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Farmington, New Mexico, United States

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New York, New York, United States

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Rochester, New York, United States

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Syracuse, New York, United States

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Charlotte, North Carolina, United States

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Charlotte, North Carolina, United States

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Bismarck, North Dakota, United States

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Fargo, North Dakota, United States

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Sayre, Pennsylvania, United States

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Upland, Pennsylvania, United States

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Providence, Rhode Island, United States

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Charleston, South Carolina, United States

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Columbia, South Carolina, United States

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Memphis, Tennessee, United States

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Houston, Texas, United States

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Burlington, Vermont, United States

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Richmond, Virginia, United States

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Adelaide, , Australia

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Box Hill, , Australia

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Brisbane, , Australia

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Camperdown, , Australia

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Fitzroy, , Australia

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Footscray, , Australia

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Kurralta Park, , Australia

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Malvern, , Australia

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Melbourne, , Australia

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Melbourne, , Australia

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Perth, , Australia

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Port Macquarie, , Australia

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St Leonards, , Australia

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Sydney, , Australia

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Sydney, , Australia

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Vienna, , Austria

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Wels, , Austria

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Jaú, , Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Kelowna, British Columbia, Canada

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North Vancouver, British Columbia, Canada

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Surrey, British Columbia, Canada

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Vancouver, British Columbia, Canada

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Victoria, British Columbia, Canada

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Winnipeg, Manitoba, Canada

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Halifax, Nova Scotia, Canada

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Hamilton, Ontario, Canada

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London, Ontario, Canada

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Mississauga, Ontario, Canada

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Oshawa, Ontario, Canada

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Ottawa, Ontario, Canada

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St. Catharines, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Toronto, Ontario, Canada

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Lévis, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Québec, Quebec, Canada

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Beijing, , China

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Beijing, , China

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Guangdong, , China

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Guangzhou, , China

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Jiangsu, , China

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Jiangxi, , China

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Shandong, , China

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Shanghai, , China

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Shanghai, , China

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Tianjin, , China

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Wuhan, , China

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Brno, , Czechia

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Chomutov, , Czechia

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Hradec Králové, , Czechia

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Ostrava, , Czechia

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Copenhagen, , Denmark

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Herlev, , Denmark

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Odense, , Denmark

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Helsinki, , Finland

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Tampere, , Finland

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Turku, , Finland

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Besançon, , France

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Bobigny, , France

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Boulogne-Billancourt, , France

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Brest, , France

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Chambray-lès-Tours, , France

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Colmar, , France

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Dijon, , France

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Grenoble, , France

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Lyon, , France

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Metz, , France

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Nice, , France

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Nice, , France

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Nîmes, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Pierre-Bénite, , France

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Rouen, , France

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Saint-Herblain, , France

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Saint-Herblain, , France

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Toulouse, , France

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Bochum, , Germany

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Halle, , Germany

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Hanover, , Germany

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Herne, , Germany

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Leipzig, , Germany

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Mainz, , Germany

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Mannheim, , Germany

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Regensburg, , Germany

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Stralsund, , Germany

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Trier, , Germany

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Hong Kong, , Hong Kong

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Budapest, , Hungary

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Budapest, , Hungary

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Győr, , Hungary

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Kecskemét, , Hungary

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Cork, , Ireland

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Dublin, , Ireland

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Dublin, , Ireland

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Galway, , Ireland

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Haifa, , Israel

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Jerusalem, , Israel

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Petah Tikva, , Israel

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Tel Aviv, , Israel

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Ẕerifin, , Israel

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Ancona, , Italy

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Genova, , Italy

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Modena, , Italy

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Padua, , Italy

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Parma, , Italy

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Pavia, , Italy

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Reggio Emilia, , Italy

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Sassari, , Italy

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Mexico City, , Mexico

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Christchurch, , New Zealand

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Bergen, , Norway

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Oslo, , Norway

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Tromsø, , Norway

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Panama City, , Panama

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Beja, , Portugal

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Lisbon, , Portugal

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San Juan, , Puerto Rico

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Cape Town, , South Africa

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Pretoria, , South Africa

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Sandton, , South Africa

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Seoul, , South Korea

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Barcelona, , Spain

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Barcelona, , Spain

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Córdoba, , Spain

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Granada, , Spain

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Leganés, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Santander, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Valencia, , Spain

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Zaragoza, , Spain

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Gävle, , Sweden

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Karlstad, , Sweden

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Stockholm, , Sweden

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Uppsala, , Sweden

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Västerås, , Sweden

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Bern, , Switzerland

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Geneva, , Switzerland

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Kueishan, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Taipei, , Taiwan

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Bangkok, , Thailand

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Bangkok, , Thailand

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Khon Kaen, , Thailand

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Aberdeen, , United Kingdom

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Birmingham, , United Kingdom

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Cardiff, , United Kingdom

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Derby, , United Kingdom

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Glasgow, , United Kingdom

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Guildford, , United Kingdom

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Hull, , United Kingdom

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London, , United Kingdom

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Maidstone, , United Kingdom

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Newcastle upon Tyne, , United Kingdom

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Northwood, , United Kingdom

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Nottingham, , United Kingdom

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Plymouth, , United Kingdom

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Salisbury, , United Kingdom

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Southampton, , United Kingdom

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Sutton, , United Kingdom

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Taunton, , United Kingdom

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Countries

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United States Australia Austria Brazil Canada China Czechia Denmark Finland France Germany Guatemala Hong Kong Hungary Ireland Israel Italy Mexico New Zealand Norway Panama Portugal Puerto Rico Russia South Africa South Korea Spain Sweden Switzerland Taiwan Thailand Turkey (Türkiye) United Kingdom

Other Identifiers

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NO16966

Identifier Type: -

Identifier Source: org_study_id

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