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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01755767




Registration number
NCT01755767
Ethics application status
Date submitted
19/12/2012
Date registered
24/12/2012

Titles & IDs
Public title
Study of Tivantinib in Subjects With Inoperable Hepatocellular Carcinoma (HCC) Who Have Been Treated With One Prior Therapy
Scientific title
A Phase 3, Randomized, Double-Blind Study of Tivantinib (ARQ 197) in Subjects With MET Diagnostic-High Inoperable Hepatocellular Carcinoma Treated With One Prior Systemic Therapy
Secondary ID [1] 0 0
2012-003308-10
Secondary ID [2] 0 0
ARQ197-A-U303
Universal Trial Number (UTN)
Trial acronym
METIV-HCC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatocellular Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

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

Experimental: Tivantinib 240 mg BID Cohort - The tivantinib dosage of 240 mg tablets administered by mouth twice daily (BID), once in the morning and once in the evening, with food, for a total daily dose of 480 mg.

Experimental: Tivantinib 120 mg BID Cohort - Tivantinib 120 mg is administered by oral tablet BID, once in the morning and once in the evening, with food, for a total daily dose of 240 mg (amended dosing group; primary analysis group).

Placebo comparator: Placebo Matching 240 mg BID Cohort - Matching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.

Placebo comparator: Placebo Matching 120 mg BID Cohort - Matching placebo is administered by oral tablet(s) BID, once in the morning and once in the evening, with food.


Treatment: Drugs: Tivantinib
Tivantinib tablets

Treatment: Drugs: Placebo
Matching placebo tablets
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Median Overall Survival (OS) Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Timepoint [1] 0 0
within 36 months
Primary outcome [2] 0 0
Overall Survival (OS) Rate At Different Time Points Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Timepoint [2] 0 0
within 36 months
Secondary outcome [1] 0 0
Progression-free Survival Following Treatment With Tivantinib 120 mg BID Compared to Placebo Group in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy (ITT Population)
Timepoint [1] 0 0
within 10 months
Secondary outcome [2] 0 0
Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Timepoint [2] 0 0
Baseline to 30 days after last dose, up to approximately 4 years
Secondary outcome [3] 0 0
Treatment-Emergent Adverse Events Reported (>20% in Tivantinib Cohort) Following Treatment With Tivantinib Compared With Placebo in Participants With MET Diagnostic-High Inoperable Hepatocellular Carcinoma (HCC) Treated With One Prior Systemic Therapy
Timepoint [3] 0 0
Baseline to 30 days after last dose, up to approximately 4 years

Eligibility
Key inclusion criteria
* Histologically confirmed HCC that is inoperable (where surgery is not indicated due to disease extension, co-morbidities, or other technical reasons), and not eligible for local therapy
* MET Diagnostic-High tissue reported by the central authorized laboratory using archival or recent biopsy tumor samples
* Received at least 4 weeks of one prior sorafenib containing systemic therapy and then experienced documented radiographic disease progression; or inability to tolerate prior therapy received for at least a minimum period of time.
* Discontinued prior systemic treatment or any investigational drug for at least 2 weeks (14 days) or for at least 3 weeks for IV anti-cancer drugs, prior to the study randomization
* Local or loco-regional therapy (i.e., surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed >= 4 weeks prior to randomization
* Measurable disease as defined by the RECIST v1.1.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* More than 1 prior systemic regimen (prior MET inhibitors/antibodies are not allowed; experimental systemic therapy for inoperable HCC given before or after sorafenib counts as separate regimen and is not allowed)
* Child-Pugh B-C cirrhotic status based on clinical findings and laboratory results
* Previous or concurrent cancer that is distinct from HCC in primary site or histology, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, and superficial bladder tumors. Any cancer curatively treated more than 3 years prior to enrollment is permitted.
* History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification within 6 months prior to study entry; active coronary artery disease (CAD); clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as greater than or equal to Grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring more than 6 months prior to study entry is permitted)
* Active clinically serious infections defined as >= Grade 3 according to NCI CTCAE
* Any medical, psychological, or social conditions, particularly if unstable, including substance abuse, that may, in the opinion of the Investigator, interfere with the subject's safety or participation in the study, protocol compliance, or evaluation of the study results
* Known human immunodeficiency virus (HIV) infection
* Blood or albumin transfusion within 5 days prior to the blood draw being used to confirm eligibility
* Concomitant interferon therapy or therapies for active Hepatitis C virus (HCV) infection
* Pregnancy or breast-feeding
* History of liver transplant
* Inability to swallow oral medications
* Clinically significant gastrointestinal bleeding occurring <= 4 weeks prior to randomization
* Pleural effusion or clinically evident (visible or palpable) ascites

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 administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
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
27/12/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/07/2017
Sample size
Target
Accrual to date
Final
383
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Heidelberg
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- Nedlands
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Heidelberg
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
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United States of America
State/province [2] 0 0
California
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United States of America
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District of Columbia
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United States of America
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Florida
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Illinois
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Kansas
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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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New Jersey
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New York
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Pennsylvania
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South Carolina
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Texas
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Washington
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Argentina
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Buenos Aires
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Argentina
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Caba
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Argentina
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Pilar
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Austria
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Graz
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Austria
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Innsbruck
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Austria
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Linz
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Austria
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Wien
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Belgium
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Brussels
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Belgium
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Ghent
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Belgium
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Leuven
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Belgium
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Liege
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Brazil
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RS
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Brazil
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SP
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Brazil
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Barretos
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Brazil
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Rio de Janeiro
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Canada
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British Columbia
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Canada
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Ontario
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France
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Amiens Cedex 1
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France
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Bordeaux Cedex
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Caen Cedex 09
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France
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Clichy
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Creteil
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Grenoble
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Lille Cedex
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France
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Marseille Cedex 09
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France
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Montpellier
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France
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Paris Cedex 12
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France
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Paris Cedex
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France
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Reims Cedex
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France
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Rennes Cedex
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France
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Toulouse Cedex 09
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France
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Villejuif Cedex
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Germany
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Aachen
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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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Duesseldorf
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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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Germany
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Hannover
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Germany
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Heidelberg
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Germany
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Leipzig
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Germany
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Magdeburg
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Germany
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Mainz
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Germany
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Muenchen
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Germany
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Munich
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Regensburg
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Tuebingen
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Ulm
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Germany
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Wuerzburg
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Italy
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Forli-Cesena
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Milano
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Italy
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Torino
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Benevento
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Bergamo
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Italy
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Bologna
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Italy
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Catania
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Italy
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Firenze
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Italy
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Modena
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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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Parma
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Italy
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Pavia
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Italy
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Pisa
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Italy
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Reggio Emilia
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Italy
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Roma
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Italy
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Turin
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Netherlands
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Amsterdam
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New Zealand
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Auckland
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Portugal
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Lisboa
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Portugal
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Porto
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Portugal
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Vila Real
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A Coruña
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Asturias
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Madrid
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Spain
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Navarra
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Spain
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Alicante
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Spain
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Barcelona
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Spain
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Cordoba
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Spain
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Sabadell
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Spain
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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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Gothenburg
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Sweden
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Stockholm
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Switzerland
State/province [103] 0 0
Bern
Country [104] 0 0
Switzerland
State/province [104] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Daiichi Sankyo
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
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
Global Clinical Leader
Address 0 0
Daiichi Sankyo
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)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT01755767