Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET
- Registration Number
- NCT01374451
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 160
- 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
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Everolimus Everolimus everolimus 10 mg once daily po alone Paseriotide LAR + Everolimus Everolimus everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im Paseriotide LAR + Everolimus Pasireotide LAR everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) Per Local Radiological Review 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.
- Secondary Outcome Measures
Name Time Method Disease Control Rate (DCR) as Per Radiology Review Once 80 PFS events had occurred 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.
Overall Survival (OS) Using Kaplan Meier Method Once 80 PFS events had occurred 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.
PFS and the Predictive Probability of Success in Phase III Once 105 PFS events had occurred occurred 105 PFS events expected after approximately 36 months
Summary of Pharmacokinetics (PK) for Everolimus for AUClast Cycle 2 Day 1 Duration of Response (DoR) Once 80 PFS events had occurred 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.
Summary of Pharmacokinetics (PK) for Everolimus for Tmax Cycle 2 Day 1 Summary of Pasireotide Concentrations Following Intramuscular Injection of Pasireotide LAR 60mg Cycle 1 Day 21, Cycle 2 Day 29 Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR Once 80 PFS events had occurred 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.
Objective Response Rate (ORR) as Per Radiology Review Once 80 PFS events had occurred 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.Summary of Pharmacokinetics (PK) for Everolimus for CL/F Cycle 2 Day 1 Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin Cycle 2 Day 1
Trial Locations
- Locations (5)
Dana Farber Cancer Institute SC-2
🇺🇸Boston, Massachusetts, United States
Montefiore Medical Center MMC
🇺🇸Bronx, New York, United States
Oregon Health & Science University Knight Cancer Institute
🇺🇸Portland, Oregon, United States
Novartis Investigative Site
🇬🇧Manchester, United Kingdom
University of Texas/MD Anderson Cancer Center UT MD Anderson Cancer Ctr
🇺🇸Houston, Texas, United States