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.
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.
Brief Title
Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET
Categories
Completion Date
Completion Date Type
Actual
Conditions
Islet Cell Tumor
Eligibility Criteria
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
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
* 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
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
Inclusion Criteria
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
inclusion/
* 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
inclusion/
Gender
All
Gender Based
false
Keywords
Pancreatic
Neuroendocrine tumors
PNET
Pasireotide
Everolimus
Advanced progressive pancreatic neuroendocrine tumor
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01374451
Org Class
Industry
Org Full Name
Novartis
Org Study Id
CSOM230I2201
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Progression-free Survival (PFS) Per Local Radiological Review
Outcome Time Frame
Once 80 PFS events had occurred aproximately after 24 months
Secondary Ids
Secondary Id
2010-023183-40
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Once 80 PFS events had occurred
Outcome Measure
Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR
Outcome Description
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.
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.
Outcome Time Frame
Once 80 PFS events had occurred
Outcome Measure
Objective Response Rate (ORR) as Per Radiology Review
Outcome Description
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.
Outcome Time Frame
Once 80 PFS events had occurred
Outcome Measure
Duration of Response (DoR)
Outcome Description
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.
Outcome Time Frame
Once 80 PFS events had occurred
Outcome Measure
Overall Survival (OS) Using Kaplan Meier Method
Outcome Description
105 PFS events expected after approximately 36 months
Outcome Time Frame
Once 105 PFS events had occurred occurred
Outcome Measure
PFS and the Predictive Probability of Success in Phase III
Outcome Description
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.
Outcome Time Frame
Once 80 PFS events had occurred
Outcome Measure
Disease Control Rate (DCR) as Per Radiology Review
Outcome Time Frame
Cycle 2 Day 1
Outcome Measure
Summary of Pharmacokinetics (PK) for Everolimus for AUClast
Outcome Time Frame
Cycle 2 Day 1
Outcome Measure
Summary of Pharmacokinetics (PK) for Everolimus for CL/F
Outcome Time Frame
Cycle 2 Day 1
Outcome Measure
Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin
Outcome Time Frame
Cycle 2 Day 1
Outcome Measure
Summary of Pharmacokinetics (PK) for Everolimus for Tmax
Outcome Time Frame
Cycle 1 Day 21, Cycle 2 Day 29
Outcome Measure
Summary of Pasireotide Concentrations Following Intramuscular Injection of Pasireotide LAR 60mg
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Steven Libutti
Investigator Email
slibutti@montefiore.org
Investigator Phone