Islet Cell TumorPhase 2COOPERATE-2NCT01374451
Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET
A Phase 2 study testing Everolimus and Pasireotide LAR in people with Islet Cell Tumor, run by Novartis Pharmaceuticals at 47 sites in 19 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Islet Cell Tumor
- What is being tested?
- Everolimus and Pasireotide LAR
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 47 sitesin 19 countries
- Study dates
- Jun 2011to Feb 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
47 sites in 19 countries.
47 sites in 19 countries
Belgium5 sites
Novartis Investigative Site
Brussels, 1070
Novartis Investigative Site
Brussels, 1200
Novartis Investigative Site
Ghent, 9000
Novartis Investigative Site
Haine-Saint-Paul, 7100
Novartis Investigative Site
Leuven, 3000
France5 sites
Novartis Investigative Site
Bordeaux, 33075
Novartis Investigative Site
Clichy, 92110
Novartis Investigative Site
Lyon, 69437
Novartis Investigative Site
Marseille, 13385
Novartis Investigative Site
Villejuif, 94805
United States4 sites
Dana Farber Cancer Institute SC-2
Boston, Massachusetts, 02115
University of Texas/MD Anderson Cancer Center UT MD Anderson Cancer Ctr
Houston, Texas, 77030-4009
Oregon Health & Science University Knight Cancer Institute
Portland, Oregon, 97239
Montefiore Medical Center MMC
The Bronx, New York, 10467
Hungary3 sites
Novartis Investigative Site
Budapest, 1062
Novartis Investigative Site
Budapest, 1085
Novartis Investigative Site
Debrecen, 4032
Italy3 sites
Novartis Investigative Site
Bologna, BO, 40138
Novartis Investigative Site
Milan, MI, 20141
Novartis Investigative Site
Modena, MO, 41100
Spain3 sites
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907
Novartis Investigative Site
Madrid, Madrid, 28041
United Kingdom3 sites
Novartis Investigative Site
Cambridge, CB2 2QQ
Novartis Investigative Site
Glasgow, G12 0YN
Novartis Investigative Site
Manchester, M20 9BX
Argentina2 sites
Novartis Investigative Site
Buenos Aires, Buenos Aires, C1264AAA
Novartis Investigative Site
Caba, Buenos Aires, C1426ANZ
Australia2 sites
Novartis Investigative Site
Herston, Queensland, 4029
Novartis Investigative Site
St Leonards, New South Wales, 2065
Brazil2 sites
Novartis Investigative Site
Rio de Janeiro, Rio de Janeiro, 20230-130
Novartis Investigative Site
São Paulo, São Paulo, 01246-000
Canada2 sites
Novartis Investigative Site
Montreal, Quebec, H1T 2M4
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
Denmark2 sites
Novartis Investigative Site
Aarhus, 8000
Novartis Investigative Site
Copenhagen N, DK-2200
Germany2 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
München, 81675
Sweden2 sites
Novartis Investigative Site
Lund, SE-221 85
Novartis Investigative Site
Uppsala, SE-751 85
Thailand2 sites
Novartis Investigative Site
Bangkok, 10330
Novartis Investigative Site
Bangkok, 10700
Turkey (Türkiye)2 sites
Novartis Investigative Site
Ankara, Turkey, 06100
Novartis Investigative Site
Istanbul, 34303
About this study
Official 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
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.
- Conditions
- Islet Cell Tumor
- Being tested
- Everolimus, Pasireotide LAR
- Keywords
- Pancreatic, Neuroendocrine tumors, PNET, Pasireotide, Everolimus, Advanced progressive pancreatic neuroendocrine tumor
- Medical subject headings
- Adenoma, Islet Cell, Neuroendocrine Tumors, Neuroectodermal Tumors, Primitive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called RAD001
Everolimus was supplied as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets
Pasireotide LARDrug
Also called SOM230 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).
| Study group | Role | What they receive |
|---|---|---|
| Paseriotide LAR + Everolimus | Experimental | everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im Receives: Drug: Everolimus; Drug: Pasireotide LAR |
| Everolimus | Experimental | everolimus 10 mg once daily po alone Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Once 80 PFS events had occurred aproximately after 24 months
Secondary outcomes (11)
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.
Measured: Once 80 PFS events had occurred
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.
Measured: Once 80 PFS events had occurred
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.
Measured: Once 80 PFS events had occurred
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.
Measured: Once 80 PFS events had occurred
PFS and the Predictive Probability of Success in Phase III
105 PFS events expected after approximately 36 months
Measured: Once 105 PFS events had occurred occurred
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.
Measured: Once 80 PFS events had occurred
Summary of Pharmacokinetics (PK) for Everolimus for AUClast
Measured: Cycle 2 Day 1
Summary of Pharmacokinetics (PK) for Everolimus for CL/F
Measured: Cycle 2 Day 1
Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin
Measured: Cycle 2 Day 1
Summary of Pharmacokinetics (PK) for Everolimus for Tmax
Measured: Cycle 2 Day 1
Summary of Pasireotide Concentrations Following Intramuscular Injection of Pasireotide LAR 60mg
Measured: Cycle 1 Day 21, Cycle 2 Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2011 (estimated)
- Study startJun 2011
- Primary completionFeb 2015
- Study completionFeb 2015
Why it stopped: The study was stopped for not meeting the primary endpoint for PFS.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Islet Cell TumorStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01374451
- Sponsor's protocol ID
- CSOM230I2201
- Other IDs
- 2010-023183-40
- Acronym
- COOPERATE-2
- Status last verified
- Oct 2016
- First submitted
- 14 Jun 2011
- Last updated
- 20 Dec 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Dec 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT01374451
- Acronym / sponsor ID
- COOPERATE-2 / CSOM230I2201
- Conditions
- Islet Cell Tumor
- Keywords
- Pancreatic, Neuroendocrine tumors, PNET, Pasireotide, Everolimus, Advanced progressive pancreatic neuroendocrine tumor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped for not meeting the primary endpoint for PFS.
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jun 2011
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 16 Jun 2011 (estimated)
- Results
- Posted 20 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Paseriotide LAR + Everolimus | Experimental | Drug: Everolimus, Drug: Pasireotide LAReverolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im |
| Everolimus | Experimental | Drug: Everolimuseverolimus 10 mg once daily po alone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: RAD001Everolimus was supplied as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets | Drug | Everolimus, Paseriotide LAR + Everolimus |
| Pasireotide LARAlso: SOM230 LARPasireotide 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). | Drug | Paseriotide LAR + Everolimus |
Primary outcome
Progression-free Survival (PFS) Per Local Radiological Review
Time frame: Once 80 PFS events had occurred aproximately after 24 months
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.
11 secondary outcomes
Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR
Time frame: Once 80 PFS events had occurred
Objective Response Rate (ORR) as Per Radiology Review
Time frame: Once 80 PFS events had occurred
Duration of Response (DoR)
Time frame: Once 80 PFS events had occurred
Overall Survival (OS) Using Kaplan Meier Method
Time frame: Once 80 PFS events had occurred
PFS and the Predictive Probability of Success in Phase III
Time frame: Once 105 PFS events had occurred occurred
Disease Control Rate (DCR) as Per Radiology Review
Time frame: Once 80 PFS events had occurred
Summary of Pharmacokinetics (PK) for Everolimus for AUClast
Time frame: Cycle 2 Day 1
Summary of Pharmacokinetics (PK) for Everolimus for CL/F
Time frame: Cycle 2 Day 1
Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin
Time frame: Cycle 2 Day 1
Summary of Pharmacokinetics (PK) for Everolimus for Tmax
Time frame: Cycle 2 Day 1
Summary of Pasireotide Concentrations Following Intramuscular Injection of Pasireotide LAR 60mg
Time frame: Cycle 1 Day 21, Cycle 2 Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Dec 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
47 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus and Pasireotide LAR in people with Islet Cell Tumor, run by Novartis Pharmaceuticals at 47 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 47 sites in Belgium, France, United States, Hungary, Italy and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival (PFS) Per Local Radiological Review (time frame: Once 80 PFS events had occurred aproximately after 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Dec 2016.