Clinical trial NCT01374451: Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Islet Cell Tumor
Keywords: Pancreatic
Neuroendocrine tumors
PNET
Pasireotide
Everolimus
Advanced progressive pancreatic neuroendocrine tumor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-06-16
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression-free Survival (PFS) Per Local Radiological Review
timeFrame: Once 80 PFS events had occurred aproximately after 24 months
Secondary outcomes:
measure: Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR
timeFrame: Once 80 PFS events had occurred
measure: Objective Response Rate (ORR) as Per Radiology Review
timeFrame: Once 80 PFS events had occurred
measure: Duration of Response (DoR)
timeFrame: Once 80 PFS events had occurred
measure: Overall Survival (OS) Using Kaplan Meier Method
timeFrame: Once 80 PFS events had occurred
measure: PFS and the Predictive Probability of Success in Phase III
timeFrame: Once 105 PFS events had occurred occurred
measure: Disease Control Rate (DCR) as Per Radiology Review
timeFrame: Once 80 PFS events had occurred
measure: Summary of Pharmacokinetics (PK) for Everolimus for AUClast
timeFrame: Cycle 2 Day 1
measure: Summary of Pharmacokinetics (PK) for Everolimus for CL/F
timeFrame: Cycle 2 Day 1
measure: Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin
timeFrame: Cycle 2 Day 1
measure: Summary of Pharmacokinetics (PK) for Everolimus for Tmax
timeFrame: Cycle 2 Day 1
measure: Summary of Pasireotide Concentrations Following Intramuscular Injection of Pasireotide LAR 60mg
timeFrame: Cycle 1 Day 21, Cycle 2 Day 29
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute SC-2
state: Massachusetts
city: Bronx
country: United States
facility: Montefiore Medical Center MMC
state: New York
city: Portland
country: United States
facility: Oregon Health & Science University Knight Cancer Institute
state: Oregon
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center UT MD Anderson Cancer Ctr
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: St. Leonards
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Herston
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Gent
country: Belgium
facility: Novartis Investigative Site
city: Haine-saint-Paul
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Rio de Janeiro
country: Brazil
facility: Novartis Investigative Site
state: RJ
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Copenhagen N
country: Denmark
facility: Novartis Investigative Site
city: Århus
country: Denmark
facility: Novartis Investigative Site
city: Bordeaux Cedex
country: France
facility: Novartis Investigative Site
city: Clichy
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Marseille cedex 05
country: France
facility: Novartis Investigative Site
city: Villejuif Cedex
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: München
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Fukuoka-city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Rotterdam
country: Netherlands
facility: Novartis Investigative Site
city: Grafton, Auckland
country: New Zealand
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Hospitalet de LLobregat
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Uppsala
country: Sweden
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Cambridge
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: