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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01374451
Registration number
NCT01374451
Ethics application status
Date submitted
14/06/2011
Date registered
16/06/2011
Date last updated
20/12/2016
Titles & IDs
Public title
Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET
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Scientific title
A Randomized, Open-label Phase II Multicenter Study Evaluating the Efficacy of Oral Everolimus Alone or in Combination With Pasireotide LAR i.m. in Advanced Progressive Pancreatic Neuroendocrine Tumors (PNET) - The COOPERATE-2 Study
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Secondary ID [1]
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2010-023183-40
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Secondary ID [2]
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CSOM230I2201
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Universal Trial Number (UTN)
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Trial acronym
COOPERATE-2
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Islet Cell Tumor
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Condition category
Condition code
Cancer
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Neuroendocrine tumour (NET)
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Cancer
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Pancreatic
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Metabolic and Endocrine
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Other endocrine disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Everolimus
Treatment: Drugs - Pasireotide LAR
Experimental: Paseriotide LAR + Everolimus - everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
Experimental: Everolimus - everolimus 10 mg once daily po alone
Treatment: Drugs: Everolimus
Everolimus was supplied as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets
Treatment: Drugs: Pasireotide LAR
Pasireotide LAR intra-muscular depot injections were supplied as a powder in vials containing 20 mg and 40 mg with ampoules containing 2 mL of vehicle (for reconstitution).
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Progression-free Survival (PFS) Per Local Radiological Review
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Assessment method [1]
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PFS per RECIST 1.0. (Response Evaluation Criteria in Solid Tumors). PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.
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Timepoint [1]
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Once 80 PFS events had occurred aproximately after 24 months
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Secondary outcome [1]
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Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR
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Assessment method [1]
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Consisted of monitoring and recording the rate, type, severity, and causal relationship of adverse events (AEs) and serious AEs (SAEs) to treatment. The safety analysis was based mainly on the frequency of AEs or SAEs and on the number of laboratory values that fell outside of pre-determined range.
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Timepoint [1]
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Once 80 PFS events had occurred
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Secondary outcome [2]
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Objective Response Rate (ORR) as Per Radiology Review
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Assessment method [2]
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Objective response was determined by the local radiologist according to the RECIST Version 1.0. ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR). This is also referred to as Overall response rate.
CR: Disappearance of all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameter of all target lesions recorded at or after baseline.
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Timepoint [2]
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Once 80 PFS events had occurred
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Secondary outcome [3]
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Duration of Response (DoR)
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Assessment method [3]
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80 PFS are expected after approximately 24 months. Kaplan Meier was initially planned to be used to depict duration of response by treatment group and by stratum. Later based on the mode of action of everolimus and pasireotide and based on study experience, only a low number of objective responses per RECIST were expected. Therefore, protocol was amended to only list duration of response, and confirmed responses were flagged in the listing. Hence, statistical analyses were not planned and such data are not available for the following table.
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Timepoint [3]
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Once 80 PFS events had occurred
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Secondary outcome [4]
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Overall Survival (OS) Using Kaplan Meier Method
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Assessment method [4]
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Overall survival was defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival was to be censored at the date of last contact.
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Timepoint [4]
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Once 80 PFS events had occurred
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Secondary outcome [5]
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PFS and the Predictive Probability of Success in Phase III
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Assessment method [5]
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105 PFS events expected after approximately 36 months
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Timepoint [5]
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Once 105 PFS events had occurred occurred
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Secondary outcome [6]
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Disease Control Rate (DCR) as Per Radiology Review
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Assessment method [6]
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Disease control rate is the percentage of patients with a best overall response of CR or PR or stable disease (SD) determined by the local radiologist according to the Response Evaluation Criteria In Solid Tumors Criteria (RECIST) Version 1.0. CR: Disappearance of all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameter of all target lesions recorded at or after baseline. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD). PD: Any progression = 18 weeks after randomization (and not qualifying for CR, PR or stable disease SD.
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Timepoint [6]
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Once 80 PFS events had occurred
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Secondary outcome [7]
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Summary of Pharmacokinetics (PK) for Everolimus for AUClast
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Assessment method [7]
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Timepoint [7]
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Cycle 2 Day 1
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Secondary outcome [8]
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Summary of Pharmacokinetics (PK) for Everolimus for CL/F
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Assessment method [8]
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Timepoint [8]
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Cycle 2 Day 1
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Secondary outcome [9]
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Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin
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Assessment method [9]
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Timepoint [9]
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Cycle 2 Day 1
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Secondary outcome [10]
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Summary of Pharmacokinetics (PK) for Everolimus for Tmax
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Assessment method [10]
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Timepoint [10]
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Cycle 2 Day 1
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Secondary outcome [11]
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Summary of Pasireotide Concentrations Following Intramuscular Injection of Pasireotide LAR 60mg
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Assessment method [11]
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Timepoint [11]
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Cycle 1 Day 21, Cycle 2 Day 29
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Eligibility
Key inclusion criteria
- Advanced histologically confirmed well differentiated pancreatic neuroendocrine tumor
- Progressive disease within the last 12 months
- Measurable disease per RECIST Version 1.0 determined by multiphase MRI or triphasic CT
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Patients currently requiring somatostatin analog treatment
- Prior therapy with mTOR inhibitors or pasireotide
- Patients with more than 2 prior systemic treatment regimens
- Previous cytotoxic chemotherapy, targeted therapy, somatostatin analogs, or biotherapy
within the last 4 weeks
Other protocol-defined inclusion/exclusion criteria may apply
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/06/2011
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/02/2015
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Sample size
Target
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Accrual to date
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Final
160
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Recruitment in Australia
Recruitment state(s)
NSW,QLD
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Recruitment hospital [1]
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Novartis Investigative Site - St. Leonards
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Recruitment hospital [2]
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Novartis Investigative Site - Herston
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Recruitment postcode(s) [1]
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2065 - St. Leonards
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Recruitment postcode(s) [2]
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4029 - Herston
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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Massachusetts
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United States of America
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State/province [2]
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New York
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United States of America
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Oregon
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United States of America
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Texas
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Country [5]
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Argentina
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State/province [5]
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Buenos Aires
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Country [6]
0
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Belgium
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State/province [6]
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Bruxelles
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Country [7]
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Belgium
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State/province [7]
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Gent
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Country [8]
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Belgium
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Haine-saint-Paul
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Country [9]
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Belgium
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State/province [9]
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Leuven
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Country [10]
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Brazil
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RJ
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Brazil
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SP
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Canada
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Ontario
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Canada
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Quebec
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Country [14]
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Denmark
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State/province [14]
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Copenhagen N
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Denmark
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State/province [15]
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Århus
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France
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Bordeaux Cedex
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France
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Clichy
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France
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Lyon
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France
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Marseille cedex 05
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France
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Villejuif Cedex
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Germany
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Berlin
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Germany
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München
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Hungary
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Budapest
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Hungary
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Debrecen
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Italy
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BO
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Italy
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MI
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Italy
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MO
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Japan
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Fukuoka
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Netherlands
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Rotterdam
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New Zealand
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Grafton, Auckland
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Spain
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Catalunya
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Spain
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Madrid
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Sweden
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Lund
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Sweden
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Uppsala
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Thailand
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Bangkok
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Turkey
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Ankara
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Turkey
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Istanbul
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United Kingdom
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Cambridge
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United Kingdom
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Glasgow
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United Kingdom
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State/province [40]
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Manchester
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Novartis Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
This study will estimate the treatment effect of everolimus in combination with pasireotide
LAR relative to everolimus alone on progression-free survival (PFS) in patients with advanced
progressive PNET.
A planned primary analysis was completed with data cut of 02-Apr-2014. The study did not meet
its primary objective, which was based on progression-free survival (PFS) as per local
radiology assessment and was prematurely terminated with the last patient last visit on
19-Feb-2015. However, it is important to note that the data did not reveal any new safety
concerns. It was decided to stop the study and this decision was shared with the study sites
on 31-Jul-2014.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01374451
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Novartis Pharmaceuticals
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Address
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Novartis Pharmaceuticals
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01374451
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