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Trial · Interventional

TerminatedPhase 2Results postedRegistry data

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

Short name COOPERATE-2

NCTNCT01374451 (opens ClinicalTrials.gov in a new tab)Other idCSOM230I2201Other id2010-023183-40
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Terminated
Phase
Phase 2
Enrollment
160 participants (actual)
Sponsor
Novartis Pharmaceuticals · Industry
Design
Randomized · Open label (no masking)
Countries
19 countries

United States, Argentina, Australia, Belgium, Brazil, Canada, Denmark, France, Germany, Hungary, Italy, Japan, Netherlands, New Zealand, Spain, Sweden, Thailand, Turkey (Türkiye), United Kingdom

Start
Jun 2011
Primary completion
Feb 2015
Completion
Feb 2015
First posted
16 Jun 2011 (estimated)
Last update posted
20 Dec 2016 (estimated)
Conditions
Islet Cell Tumor

Timeline

1 trial · 1 stopped early · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201120122013201420152016
  1. Ph 2

    COOPERATE-2

    NCT01374451

    Jun 2011 to Feb 2015

    Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • EverolimusDrug
  • Pasireotide LARDrug

Arms2

  • Experimental

    Paseriotide LAR + Everolimus

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

  • Experimental

    Everolimus

    everolimus 10 mg once daily po alone

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Progression-free Survival (PFS) Per Local Radiological Review

    Time frame · Once 80 PFS events had occurred aproximately after 24 months

    Registry 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.

Secondary outcomes(11)

  1. Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR

    Time frame · Once 80 PFS events had occurred

    Registry 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.

  2. Objective Response Rate (ORR) as Per Radiology Review

    Time frame · Once 80 PFS events had occurred

    Registry 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.

  3. Duration of Response (DoR)

    Time frame · Once 80 PFS events had occurred

    Registry 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.

  4. Overall Survival (OS) Using Kaplan Meier Method

    Time frame · Once 80 PFS events had occurred

    Registry 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.

  5. PFS and the Predictive Probability of Success in Phase III

    Time frame · Once 105 PFS events had occurred occurred

    Registry description

    105 PFS events expected after approximately 36 months

  6. Disease Control Rate (DCR) as Per Radiology Review

    Time frame · Once 80 PFS events had occurred

    Registry 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.

  7. Summary of Pharmacokinetics (PK) for Everolimus for AUClast

    Time frame · Cycle 2 Day 1

  8. Summary of Pharmacokinetics (PK) for Everolimus for CL/F

    Time frame · Cycle 2 Day 1

  9. Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin

    Time frame · Cycle 2 Day 1

  10. Summary of Pharmacokinetics (PK) for Everolimus for Tmax

    Time frame · Cycle 2 Day 1

  11. Summary of Pasireotide Concentrations Following Intramuscular Injection of Pasireotide LAR 60mg

    Time frame · Cycle 1 Day 21, Cycle 2 Day 29

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMedian· Once 80 PFS events had occurred aproximately after 24 months

Progression-free Survival (PFS) Per Local Radiological Review

GroupValue (months)
Paseriotide LAR + Everolimus16.82
Everolimus16.59
Secondary and other outcome results(7)
Secondary outcomeNumber· Once 80 PFS events had occurred

Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR

GroupValue (Participants)
Paseriotide LAR + Everolimus7
Everolimus10
Secondary outcomeNumber· Once 80 PFS events had occurred

Objective Response Rate (ORR) as Per Radiology Review

GroupValue (Percentage of participants)
Paseriotide LAR + Everolimus20.3
Everolimus6.2
Secondary outcome· Once 80 PFS events had occurred

Duration of Response (DoR)

GroupValue
Paseriotide LAR + Everolimusnot posted
Everolimusnot posted
Secondary outcomeNumber· Once 80 PFS events had occurred

Overall Survival (OS) Using Kaplan Meier Method

GroupValue (Percentage of participants)
Paseriotide LAR + Everolimus93.5
Everolimus93.7
Secondary outcome· Once 105 PFS events had occurred occurred

PFS and the Predictive Probability of Success in Phase III

GroupValue
Paseriotide LAR + Everolimusnot posted
Everolimusnot posted
Secondary outcomeNumber· Once 80 PFS events had occurred

Disease Control Rate (DCR) as Per Radiology Review

GroupValue (Percentage of participants)
Paseriotide LAR + Everolimus77.2
Everolimus82.7
Secondary outcomeMean· Cycle 2 Day 1

Summary of Pharmacokinetics (PK) for Everolimus for AUClast

GroupValue (ng*hr/mL)Spread
Paseriotide LAR + Everolimus51191.8
Everolimus378123

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Everolimus LAR + Pasireotideeverolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im–41 / 7877 / 78
Everolimuseverolimus 10 mg once daily po alone–49 / 8180 / 81

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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

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