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Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET (COOPERATE-2)

This study has been terminated.
(The study was stopped for not meeting the primary endpoint for PFS.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01374451
First received: June 14, 2011
Last updated: October 26, 2016
Last verified: October 2016
June 14, 2011
October 26, 2016
June 2011
February 2015   (Final data collection date for primary outcome measure)
Progression-free Survival (PFS) Per Local Radiological Review [ Time Frame: 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.
Treatment effect on progression-free survival (PFS) per RECIST 1.0 [ Time Frame: Once 80 PFS events have occurred ]

PFS(progression-free survival) RECIST(Response Evaluation Criteria in Solid Tumors)

80 PFS events are expected after approximately 24 months

Complete list of historical versions of study NCT01374451 on ClinicalTrials.gov Archive Site
  • Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR [ Time Frame: 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 [ Time Frame: 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.

  • Duration of Response (DoR) [ Time Frame: 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.
  • Overall Survival (OS) Using Kaplan Meier Method [ Time Frame: 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 [ Time Frame: Once 105 PFS events had occurred occurred ]
    105 PFS events expected after approximately 36 months
  • Disease Control Rate (DCR) as Per Radiology Review [ Time Frame: 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.
  • Summary of Pharmacokinetics (PK) for Everolimus for AUClast [ Time Frame: Cycle 2 Day 1 ]
  • Summary of Pharmacokinetics (PK) for Everolimus for CL/F [ Time Frame: Cycle 2 Day 1 ]
  • Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin [ Time Frame: Cycle 2 Day 1 ]
  • Summary of Pharmacokinetics (PK) for Everolimus for Tmax [ Time Frame: Cycle 2 Day 1 ]
  • Summary of Pasireotide Concentrations Following Intramuscular Injection of Pasireotide LAR 60mg [ Time Frame: Cycle 1 Day 21, Cycle 2 Day 29 ]
  • Safety and tolerability profile of Everolimus alone or in combination with Pasireotide LAR [ Time Frame: Once 80 PFS events have occurred ]
    80 PFS events are expected after approximately 24 months.
  • Objective Response Rate (ORR) and Disease Control Rate (DCR) [ Time Frame: Once 80 PFS events have occurred ]
    80 PFS are expected after approximately 24 months
  • Duration of response (DoR) [ Time Frame: Once 80 PFS events have occurred ]
    80 PFS are expected after approximately 24 months
  • Overall Survival (OS) [ Time Frame: Once 80 PFS events have occurred ]
    80 PFS events expected after approximately 24 months.
  • The treatment effect on PFS and to assess the predictive probability of success in a possible subsequent phase III study once 105 PFS events have been observed [ Time Frame: Once 105 PFS events have occurred ]
    105 PFS events expected after approximately 36 months
Not Provided
Not Provided
 
Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Islet Cell Tumor
  • Drug: Everolimus
    Everolimus was supplied as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets
    Other Name: RAD001
  • 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).
    Other Name: SOM230 LAR
  • Experimental: Paseriotide LAR + Everolimus
    everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
    Interventions:
    • Drug: Everolimus
    • Drug: Pasireotide LAR
  • Experimental: Everolimus
    everolimus 10 mg once daily po alone
    Intervention: Drug: Everolimus
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
160
February 2015
February 2015   (Final data collection date for primary outcome measure)

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

Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Argentina,   Australia,   Belgium,   Brazil,   Canada,   Denmark,   France,   Germany,   Hungary,   Italy,   Japan,   Netherlands,   New Zealand,   Spain,   Sweden,   Thailand,   Turkey,   United Kingdom,   United States
 
 
NCT01374451
CSOM230I2201
2010-023183-40 ( EudraCT Number )
Yes
Not Provided
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP