Efficacy Of Everolimus Alone Or In Combination With Pasireotide LAR In Advanced PNET

Study Overview

Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET

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.

N/A

Islet Cell Tumor

DRUG: Everolimus
DRUG: Pasireotide LAR

CSOM230I2201
2010-023183-40 (EUDRACT_NUMBER Identifier) (EUDRACT_NUMBER: )

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-06-14	Results First Submitted 2016-02-16	Last Update Submitted that met QC Criteria 2016-10-26
First Submitted that Met QC Criteria 2011-06-15	Results First Submitted that Met QC Criteria 2016-10-26	Last Update Posted (ESTIMATED) 2016-12-20
First Posted (ESTIMATED) 2011-06-16	Results First Posted 2016-12-20	Last Verified 2016-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Paseriotide LAR + Everolimus everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im	DRUG: Everolimus Everolimus was supplied as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets DRUG: 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).
EXPERIMENTAL: Everolimus everolimus 10 mg once daily po alone	DRUG: Everolimus Everolimus was supplied as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets DRUG: 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).

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Paseriotide LAR + Everolimus

everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im

DRUG: Everolimus

Everolimus was supplied as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets

DRUG: 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).

EXPERIMENTAL: Everolimus

everolimus 10 mg once daily po alone

DRUG: Everolimus

Everolimus was supplied as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets

DRUG: 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).

Primary Outcome Measures	Measure Description	Time Frame
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.	Once 80 PFS events had occurred aproximately after 24 months

Secondary Outcome Measures	Measure Description	Time Frame
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.	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.	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.	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.	Once 80 PFS events had occurred
PFS and the Predictive Probability of Success in Phase III	105 PFS events expected after approximately 36 months	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.	Once 80 PFS events had occurred
Summary of Pharmacokinetics (PK) for Everolimus for AUClast		Cycle 2 Day 1
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
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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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