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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/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
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
Secondary ID [1] 0 0
2010-023183-40
Secondary ID [2] 0 0
CSOM230I2201
Universal Trial Number (UTN)
Trial acronym
COOPERATE-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Islet Cell Tumor 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Pancreatic
Metabolic and Endocrine 0 0 0 0
Other endocrine disorders

Intervention/exposure
Study type
Interventional
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).

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

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Per Local Radiological Review - 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.
Timepoint [1] 0 0
Once 80 PFS events had occurred aproximately after 24 months
Secondary outcome [1] 0 0
Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR - 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.
Timepoint [1] 0 0
Once 80 PFS events had occurred
Secondary outcome [2] 0 0
Objective Response Rate (ORR) as Per Radiology Review - 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.
Timepoint [2] 0 0
Once 80 PFS events had occurred
Secondary outcome [3] 0 0
Duration of Response (DoR) - 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.
Timepoint [3] 0 0
Once 80 PFS events had occurred
Secondary outcome [4] 0 0
Overall Survival (OS) Using Kaplan Meier Method - 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.
Timepoint [4] 0 0
Once 80 PFS events had occurred
Secondary outcome [5] 0 0
PFS and the Predictive Probability of Success in Phase III - 105 PFS events expected after approximately 36 months
Timepoint [5] 0 0
Once 105 PFS events had occurred occurred
Secondary outcome [6] 0 0
Disease Control Rate (DCR) as Per Radiology Review - 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.
Timepoint [6] 0 0
Once 80 PFS events had occurred
Secondary outcome [7] 0 0
Summary of Pharmacokinetics (PK) for Everolimus for AUClast
Timepoint [7] 0 0
Cycle 2 Day 1
Secondary outcome [8] 0 0
Summary of Pharmacokinetics (PK) for Everolimus for CL/F
Timepoint [8] 0 0
Cycle 2 Day 1
Secondary outcome [9] 0 0
Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin
Timepoint [9] 0 0
Cycle 2 Day 1
Secondary outcome [10] 0 0
Summary of Pharmacokinetics (PK) for Everolimus for Tmax
Timepoint [10] 0 0
Cycle 2 Day 1
Secondary outcome [11] 0 0
Summary of Pasireotide Concentrations Following Intramuscular Injection of Pasireotide LAR 60mg
Timepoint [11] 0 0
Cycle 1 Day 21, Cycle 2 Day 29

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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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

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
Terminated
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)
NSW,QLD
Recruitment hospital [1] 0 0
Novartis Investigative Site - St. Leonards
Recruitment hospital [2] 0 0
Novartis Investigative Site - Herston
Recruitment postcode(s) [1] 0 0
2065 - St. Leonards
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Massachusetts
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Oregon
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
Argentina
State/province [5] 0 0
Buenos Aires
Country [6] 0 0
Belgium
State/province [6] 0 0
Bruxelles
Country [7] 0 0
Belgium
State/province [7] 0 0
Gent
Country [8] 0 0
Belgium
State/province [8] 0 0
Haine-saint-Paul
Country [9] 0 0
Belgium
State/province [9] 0 0
Leuven
Country [10] 0 0
Brazil
State/province [10] 0 0
RJ
Country [11] 0 0
Brazil
State/province [11] 0 0
SP
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
Denmark
State/province [14] 0 0
Copenhagen N
Country [15] 0 0
Denmark
State/province [15] 0 0
Århus
Country [16] 0 0
France
State/province [16] 0 0
Bordeaux Cedex
Country [17] 0 0
France
State/province [17] 0 0
Clichy
Country [18] 0 0
France
State/province [18] 0 0
Lyon
Country [19] 0 0
France
State/province [19] 0 0
Marseille cedex 05
Country [20] 0 0
France
State/province [20] 0 0
Villejuif Cedex
Country [21] 0 0
Germany
State/province [21] 0 0
Berlin
Country [22] 0 0
Germany
State/province [22] 0 0
München
Country [23] 0 0
Hungary
State/province [23] 0 0
Budapest
Country [24] 0 0
Hungary
State/province [24] 0 0
Debrecen
Country [25] 0 0
Italy
State/province [25] 0 0
BO
Country [26] 0 0
Italy
State/province [26] 0 0
MI
Country [27] 0 0
Italy
State/province [27] 0 0
MO
Country [28] 0 0
Japan
State/province [28] 0 0
Fukuoka
Country [29] 0 0
Netherlands
State/province [29] 0 0
Rotterdam
Country [30] 0 0
New Zealand
State/province [30] 0 0
Grafton, Auckland
Country [31] 0 0
Spain
State/province [31] 0 0
Catalunya
Country [32] 0 0
Spain
State/province [32] 0 0
Madrid
Country [33] 0 0
Sweden
State/province [33] 0 0
Lund
Country [34] 0 0
Sweden
State/province [34] 0 0
Uppsala
Country [35] 0 0
Thailand
State/province [35] 0 0
Bangkok
Country [36] 0 0
Turkey
State/province [36] 0 0
Ankara
Country [37] 0 0
Turkey
State/province [37] 0 0
Istanbul
Country [38] 0 0
United Kingdom
State/province [38] 0 0
Cambridge
Country [39] 0 0
United Kingdom
State/province [39] 0 0
Glasgow
Country [40] 0 0
United Kingdom
State/province [40] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/show/NCT01374451
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
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
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01374451