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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01693068




Registration number
NCT01693068
Ethics application status
Date submitted
14/09/2012
Date registered
26/09/2012
Date last updated
5/01/2018

Titles & IDs
Public title
Phase II Trial of Pimasertib Versus Dacarbazine in N-Ras Mutated Cutaneous Melanoma
Scientific title
A Multicenter, Open Label, Randomized Phase II Trial of the MEK Inhibitor Pimasertib or Dacarbazine in Previously Untreated Subjects With N-Ras Mutated Locally Advanced or Metastatic Malignant Cutaneous Melanoma
Secondary ID [1] 0 0
2012-002669-37
Secondary ID [2] 0 0
EMR 200066-007
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
N-Ras Mutated Locally Advanced or Metastasis Malignant Cutaneous Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Non melanoma skin cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pimasertib
Treatment: Drugs - Dacarbazine

Experimental: Pimasertib -

Active comparator: Dacarbazine -


Treatment: Drugs: Pimasertib
Subjects will receive pimasertib orally as monotherapy at a dose of 60 milligram (mg) twice daily continuously. Treatment will consist of repeated 21-day cycles which will continue until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurs first.

Treatment: Drugs: Dacarbazine
Subjects will receive dacarbazine intravenously at dose of 1000 milligram per square meter (mg/m\^2) of body surface area every 3 weeks on Day 1 of each 21-days cycle until progression of the disease, unacceptable toxicity, withdrawal of informed consent, or death, whichever occurs first. Eligible subjects with documented tumor progression on dacarbazine will offer to switch to pimasertib treatment.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS)
Timepoint [1] 0 0
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut-off date (04-Jul-2015)
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Timepoint [1] 0 0
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut-off date (04-Jul-2015)
Secondary outcome [2] 0 0
Disease Control Rate (DCR)
Timepoint [2] 0 0
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to cut-off date (04-Jul-2015)
Secondary outcome [3] 0 0
Percentage of Subjects With Progression-free Survival (PFS) at 6 Months
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
From date of randomization until date of death from any cause, assessed up to cut-off date (04-Jul-2015)
Secondary outcome [5] 0 0
Percentage of Subjects With Overall Survival (OS) at 12 Months
Timepoint [5] 0 0
12 months
Secondary outcome [6] 0 0
Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Total Score (FACT-M TS) at Day 1 of Pre-Specified Cycles and End of Treatment (EOT)
Timepoint [6] 0 0
Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 35, 36, 37 and EOT (up to cut-off date [04-Jul-2015])
Secondary outcome [7] 0 0
Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Trial Outcome Index (FACT-M TOI) at Day 1 of Pre-Specified Cycles and End of Treatment (EOT)
Timepoint [7] 0 0
Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 30, 31, 32, 33, 35, 36, 37 and EOT (up to cut-off date [04-Jul-2015])
Secondary outcome [8] 0 0
Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation or TEAEs Leading to Death
Timepoint [8] 0 0
Baseline up to cut-off date (04-Jul-2015)
Secondary outcome [9] 0 0
Number of Subjects With Adverse Events (AEs) of Special Interest
Timepoint [9] 0 0
Baseline up to cut-off date (04-Jul-2015)
Secondary outcome [10] 0 0
Number of Subjects With Clinically Significant Change From Baseline in Laboratory Parameter, Vital Signs, Electrocardiogram (ECG) and Ophthalmologic Findings
Timepoint [10] 0 0
Baseline up to cut-off date (04-Jul-2015)

Eligibility
Key inclusion criteria
* Subjects with measurable, histologically or cytologically confirmed, locally advanced or metastatic cutaneous melanoma (stage III c or M1ac) N-Ras mutated. If N-Ras mutational status is unknown at screening, it must be prospectively defined before inclusion. If N-Ras mutational status is already known before screening, it must be retrospectively confirmed after inclusion by the sponsor.
* Tumor lesions amenable to biopsy or available tumor tissue as archival samples.
* Age greater than or equal to (>=) 18 years.
* Has read and understood the informed consent form and is willing and able to give informed consent. Fully understands requirements of the trial and willing to comply with all trial visits and assessments.
* Women of childbearing potential must have a negative blood pregnancy test at the screening visit. For the purposes of this trial, women of childbearing potential are defined as: "All female subjects after puberty unless they are post-menopausal for at least two years, or are surgically sterile".
* Female subjects of childbearing potential and male subjects with female partners of childbearing potential must be willing to avoid pregnancy by using an adequate method of contraception for 2 weeks prior to, during and four weeks after the last dose of trial medication. Effective contraception is defined as the method of contraception with a failure rate of less than 1% per year. Adequate contraception is defined as follows: two barrier methods or one barrier method with a spermicidal or intrauterine device or oral contraception for female partners of male subjects.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has previous systemic treatment for locally advanced or metastatic cutaneous melanoma (excluding adjuvant treatment).
* Has non-measurable lesions, disease not evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1
* Has an Eastern Cooperative Oncology Group performance status (ECOG PS) >1.
* Has bone marrow impairment as evidenced by Hemoglobin <10.0 g/dL, Neutrophil count <1.5 * 10^9/L, platelets <100 * 10^9/L.
* Has renal impairment as evidenced by calculated creatinine clearance <60 mL/min (according to the Cockcroft-Gault formula).
* Has liver function abnormality as defined by total bilirubin >1.5 * Upper Limit of Normal (ULN), or aspartate aminotransferase (AST)/alanine aminotransferase (ALT) >2.5 * ULN, for subjects with liver involvement AST/ALT >5 * ULN.
* Has significant cardiac conduction abnormalities, including QTc prolongation of >480 milliseconds and/or pacemaker or clinically relevant impaired cardiovascular function.
* Has hypertension uncontrolled by medication
* Has retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), history of uveitis, or history of retinal vein occlusion (RVO) or any eye condition that would be considered a risk factor for RVO (e.g., uncontrolled glaucoma or ocular hypertension).
* Has known active central nervous system (CNS) metastases unless previously radiotherapy treated, stable by CT scan for at least 3 months without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants.
* History of difficulty swallowing, malabsorption or other chronic gastro-intestinal disease, or conditions that may hamper compliance and/or absorption of the tested product.
* Known human immunodeficiency virus (HIV) positivity, active hepatitis C, or active hepatitis B.
* Has undergone surgical intervention within 28 days from Day 1 of trial drug treatment.
* Has received extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from Day 1 of trial drug treatment.
* Has history of any other significant medical disease such as major gastric or small bowel surgery, recent drainage of significant volumes of ascites or pleural effusion or has a psychiatric condition that might impair the subject well-being or preclude full participation in the trial.
* Has known hypersensitivity to dacarbazine.
* Is a pregnant or nursing female.
* Participated in another clinical trial within the past 28 days.
* Has creatine phosphokinase (CPK) level at baseline National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade >=2 (i.e > 2.5 * ULN), and/or has a previous history of myositis or rhabdomyolysis.
* Is suitable for treatment with an approved B-Raf inhibitor (exclusion criteria implemented in German amendment only).

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 2
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
5/12/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
24/10/2016
Sample size
Target
Accrual to date
Final
194
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Adelaide, SA
Recruitment hospital [2] 0 0
Research Site - Albury/Wodonga
Recruitment hospital [3] 0 0
Research Site - Auchenflower
Recruitment hospital [4] 0 0
Research Site - Box Hill
Recruitment hospital [5] 0 0
Research Site - Greenslopes
Recruitment hospital [6] 0 0
Research Site - Herston
Recruitment hospital [7] 0 0
Research Site - Malvern
Recruitment hospital [8] 0 0
Research Site - North Sydney
Recruitment hospital [9] 0 0
Research Site - Prahran
Recruitment hospital [10] 0 0
Research Site - Wendouree
Recruitment hospital [11] 0 0
Research Site - Woodville South
Recruitment hospital [12] 0 0
Research site - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Adelaide, SA
Recruitment postcode(s) [2] 0 0
- Albury/Wodonga
Recruitment postcode(s) [3] 0 0
- Auchenflower
Recruitment postcode(s) [4] 0 0
- Box Hill
Recruitment postcode(s) [5] 0 0
- Greenslopes
Recruitment postcode(s) [6] 0 0
- Herston
Recruitment postcode(s) [7] 0 0
- Malvern
Recruitment postcode(s) [8] 0 0
- North Sydney
Recruitment postcode(s) [9] 0 0
- Prahran
Recruitment postcode(s) [10] 0 0
- Wendouree
Recruitment postcode(s) [11] 0 0
- Woodville South
Recruitment postcode(s) [12] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
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
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Belgium
State/province [14] 0 0
Brussel
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Belgium
State/province [16] 0 0
Edegem
Country [17] 0 0
France
State/province [17] 0 0
Bordeaux
Country [18] 0 0
France
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Brest
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France
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Dijon
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France
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Lille
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France
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Lyon
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France
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Marseille
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France
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Montpellier
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France
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Nantes
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France
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Paris
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France
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Pierre Benite
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France
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Rennes
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France
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Toulouse
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France
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Villejuif
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Germany
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Augsburg
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Germany
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Berlin
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Germany
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Bonn
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Germany
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Buxtehude
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Germany
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Düsseldorf
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Germany
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Erlangen
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Germany
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Essen
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Germany
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Frankfurt am Main
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Germany
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Hamburg
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Hannover
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Kiel
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Germany
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Köln
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Leipzig
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Magdeburg
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Mainz
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Germany
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München
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Germany
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Münster
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Germany
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Plauen
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Germany
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Tübingen
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Germany
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Würzburg
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Israel
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Jerusalem
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Israel
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Ramat-Gan
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Israel
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Tel-Aviv
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Italy
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Bari
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Italy
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Genova
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Italy
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Meldola - FC
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Italy
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Milano
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Italy
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Napoli
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Italy
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Padova
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Italy
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Roma
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Italy
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Siena
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Netherlands
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Groningen
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Rotterdam
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Netherlands
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Utrecht
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New Zealand
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Christchurch
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New Zealand
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Hamilton
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New Zealand
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Palmerston North
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New Zealand
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Tauranga
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South Africa
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Durban
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South Africa
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Johannesburg
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South Africa
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Pietermaritzburg
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South Africa
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Pretoria
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Spain
State/province [72] 0 0
Badalona
Country [73] 0 0
Spain
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Barcelona
Country [74] 0 0
Spain
State/province [74] 0 0
l'Hospitalet de Llobregat
Country [75] 0 0
Spain
State/province [75] 0 0
Madrid
Country [76] 0 0
Spain
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Majadahonda
Country [77] 0 0
Spain
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Málaga
Country [78] 0 0
Spain
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Pamplona
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Spain
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Sevilla
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Sweden
State/province [80] 0 0
Göteborg
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Sweden
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Stockholm
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Switzerland
State/province [82] 0 0
Basel
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Switzerland
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Zürich
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United Kingdom
State/province [84] 0 0
Cambridge
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United Kingdom
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London
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United Kingdom
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Manchester
Country [87] 0 0
United Kingdom
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Newcastle upon Tyne
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
EMD Serono
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Merck KGaA, Darmstadt, Germany
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Study Director
Address 0 0
EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
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.

Results are available at https://clinicaltrials.gov/study/NCT01693068