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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00022672




Registration number
NCT00022672
Ethics application status
Date submitted
10/08/2001
Date registered
27/01/2003
Date last updated
13/06/2013

Titles & IDs
Public title
A Study to Evaluate the Efficacy and Safety of Herceptin® (Trastuzumab) in Combination With Arimidex® (Anastrozole) an Aromatase Inhibitor Compared to Arimidex® Alone in Patients With Metastatic Breast Cancer
Scientific title
A Randomized, Open-label Study of the Effect of Herceptin Plus Arimidex Compared With Arimidex Alone on Progression-free Survival in Patients With HER2-positive and Hormone-receptor Positive Metastatic Breast Cancer
Secondary ID [1] 0 0
BO16216
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - trastuzumab (Herceptin®)
Treatment: Drugs - anastrazole (Arimidex®)

Experimental: trastuzumab + anastrozole - Trastuzumab 4 mg/kg loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes plus 1 mg oral dose of anastrozole every day for 24 Months in the Main phase and in the Extension Phase.

Active Comparator: anastrozole - 1 mg oral dose of anastrozole every day for 24 Months in the Main phase. In the Extension Phase participants could cross-over to also receive trastuzumab 4 mg/kg initial loading dose intravenous (iv) over 90 minutes, followed by weekly doses of 2 mg/kg iv over 30 minutes.


Treatment: Drugs: trastuzumab (Herceptin®)
4mg/kg iv loading dose, followed by 2mg/kg iv weekly

Treatment: Drugs: anastrazole (Arimidex®)
1 mg tablet taken orally daily

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

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) - PFS was assessed by the investigator based on World Health Organization (WHO) criteria using radiographic tumor evaluations. Disease progression was defined as the appearance of any new lesion not previously identified or an estimated increase of 25% or more in existent bidimensionally or unidimensionally measurable lesions or progression of an existing non-measurable lesion. For bidimensionally measurable malignant lesions with an area of at least 2.0 centimeters squared (cm^2) an increase of 1.0 cm^2 was required and for unidimensionally measurable lesions of 1.0 cm or less an increase of 0.5 cm was required. PFS was defined as the number of days between date of randomization and date of documented disease progression or date of death. Kaplan Meier estimates of PFS are presented.
Timepoint [1] 0 0
24 Months, End of Study (Up to 5 years)
Secondary outcome [1] 0 0
Percentage of Participants With Clinical Benefit - Clinical Benefit was defined as stable disease for = six months or complete response or partial response.
Timepoint [1] 0 0
24 Months, End of Study (Up to 5 years)
Secondary outcome [2] 0 0
Duration of Response at 24 Months - Duration of response was defined as the number of days from the day complete response or partial response was first noted to the day of progression of disease, death or last follow-up.
Timepoint [2] 0 0
24 Months
Secondary outcome [3] 0 0
Time to Response at 24 Months - Time to response was defined as the number of days from the day of randomization to the day complete response or partial response was first noted.
Timepoint [3] 0 0
24 Months
Secondary outcome [4] 0 0
Overall Survival at 24 Months - Overall Survival is defined as the number of days from randomization to death.
Timepoint [4] 0 0
24 Months
Secondary outcome [5] 0 0
Percentage of Participants With Two-Year Survival
Timepoint [5] 0 0
24 Months
Secondary outcome [6] 0 0
Percentage of Participants With Overall Tumor Response at 24 Months - Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Overall Response was defined as either complete response or partial response.
Timepoint [6] 0 0
24 Months
Secondary outcome [7] 0 0
Percentage of Participants With Best Tumor Response at 24 Months - Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Best Response was defined as the best response a patient achieves in the study.
Timepoint [7] 0 0
24 Months
Secondary outcome [8] 0 0
Percentage of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status at Final Visit Compared to Baseline - Participants rated their performance status using the ECOG Questionnaire on the following scale: 0=Fully active, perform all pre-disease activities without restriction; 1=Restricted in physically strenuous activity but ambulatory, carry out work of a light or sedentary nature; 2=Ambulatory, capable of self-care, unable to carry out any work activities, up and about more than >50% of waking hours; 3=Capable of limited self-care, confined to bed or chair >50% of waking hours; 4=Completely disabled, not capable of any self-care, totally confined to bed or chair; 5=Dead.
The percentage of participants in the following categories:
Improved: Score decrease from baseline. Unchanged: Score the same as baseline. Worse: Score increase from baseline.
Timepoint [8] 0 0
Baseline, Final Visit (Up to 24 Months)
Secondary outcome [9] 0 0
Duration of Response at End of Study - Duration of response was defined as the number of days from the day complete response or partial response was first noted to the day of progression of disease, death or last follow-up.
Timepoint [9] 0 0
End of Study (Up to 5 years)
Secondary outcome [10] 0 0
Time to Response at End of Study - Time to response was defined as the number of days from the day of randomization to the day complete response or partial response was first noted.
Timepoint [10] 0 0
End of Study (Up to 5 years)
Secondary outcome [11] 0 0
Percentage of Participants With Overall Tumor Response at End of Study - Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Overall Response was defined as either complete response or partial response.
Timepoint [11] 0 0
End of Study (Up to 5 years)
Secondary outcome [12] 0 0
Percentage of Participants With Best Tumor Response at End of Study - Tumor Response levels were determined by the investigator and an Independent Response Evaluation Committee and Reconciled. Best Response was defined as the best response a patient achieves in the study.
Timepoint [12] 0 0
End of Study (Up to 5 years)
Secondary outcome [13] 0 0
Number of Participants With Adverse Events - Number of participants with adverse events as a measure for safety as assessed by the collection of adverse events, laboratory tests for Hematology and Serum Chemistry, clinical assessments and cardiac monitoring.
Timepoint [13] 0 0
Throughout the Study (Up to 5 years)

Eligibility
Key inclusion criteria
- postmenopausal women;

- metastatic breast cancer suitable for endocrine therapy;

- positive hormone receptor status;

- Human epidermal growth factor receptor 2 (HER2) overexpression.
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- patients on hormone replacement therapy;

- previous chemotherapy for metastatic disease;

- uncontrolled cardiac disease and history of cardiac failure.

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
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
- Box Hill
Recruitment hospital [2] 0 0
- Darlinghurst
Recruitment hospital [3] 0 0
- Waratah
Recruitment postcode(s) [1] 0 0
3128 - Box Hill
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment outside Australia
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United States of America
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Arizona
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Illinois
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Kansas
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Maine
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Michigan
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Nebraska
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Ohio
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Pennsylvania
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Brazil
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Porto Alegre
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Bulgaria
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Plovdiv
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Bulgaria
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Sofia
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Bulgaria
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Stara Zagora
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Ontario
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Beijing
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Shanghai
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China
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Wuhan
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France
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Avignon
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France
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Nice
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Germany
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Frankfurt
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Germany
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Kiel
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Germany
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München
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Germany
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Trier
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Hong Kong
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Hong Kong
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Hungary
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Budapest
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India
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Ahmedabad
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India
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Bangalore
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India
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Chennai
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India
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Cuttack
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India
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Ludhiana
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India
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Mumbai
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India
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New Delhi
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Israel
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Haifa
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Israel
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Petach Tikva
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Israel
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Ramat-gan
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Israel
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Rehovot
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Israel
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Tel Aviv
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Italy
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Genova
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Lithuania
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Vilnius
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Mexico
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Guadalajara
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Mexico
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Mexico City
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Netherlands
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Amsterdam
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Rotterdam
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Trondheim
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Bialystok
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Gliwice
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Krakow
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Lodz
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Szczecin
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Russian Federation
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Barnaul
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Russian Federation
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Izhevsk
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Russian Federation
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Kazan
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Krasnodar
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St Petersburg
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Russian Federation
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UFA
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South Africa
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Floracliffe
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South Africa
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Pretoria
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Barcelona
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Córdoba
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Girona
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Mataro
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Reus
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Valencia
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Boras
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Gaelve
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Taipei
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Taoyuan
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Ankara
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Istanbul
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Izmir
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Turkey
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Shhiye, Ankara
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Ukraine
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Kiev
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Ukraine
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Lvov
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Ukraine
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Odessa
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Ukraine
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Sumy
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Ukraine
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Zaporozhye
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United Kingdom
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Cardiff
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Edinburgh
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Guildford
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Ipswich
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London
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Manchester
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United Kingdom
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Merseyside
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United Kingdom
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Newcastle Upon Tyne
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Southampton
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United Kingdom
State/province [101] 0 0
Swansea

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This 2 arm study assessed the safety and efficacy of adding intravenous trastuzumab
(Herceptin®) to daily oral anastrozole (Arimidex®) tablets as first- and second-line
treatment in postmenopausal patients with human epidermal growth factor receptor-2 (HER2)
overexpressing metastatic breast cancer (ER+ve and/or PR+ve). Patients were randomized to
receive either anastrazole 1 mg per os (po) daily, or anastrazole 1 mg po daily + a loading
dose of Herceptin® 4 mg/kg intravenous (iv) followed by weekly doses of Herceptin® 2 mg/kg
iv. The anticipated time on study treatment was until disease progression, and the target
sample size was 100-500 individuals.
Trial website
https://clinicaltrials.gov/show/NCT00022672
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

Summary results
Other publications