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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
  Purpose

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.


Condition Intervention Phase
Islet Cell Tumor
Drug: Everolimus
Drug: Pasireotide LAR
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 160
Study Start Date: June 2011
Study Completion Date: February 2015
Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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: 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
Other Name: RAD001

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01374451

  Show 47 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01374451     History of Changes
Other Study ID Numbers: CSOM230I2201
2010-023183-40 ( EudraCT Number )
Study First Received: June 14, 2011
Results First Received: February 16, 2016
Last Updated: October 26, 2016

Keywords provided by Novartis:
Pancreatic
Neuroendocrine tumors
PNET
Pasireotide
Everolimus
Advanced progressive pancreatic neuroendocrine tumor

Additional relevant MeSH terms:
Neuroendocrine Tumors
Carcinoid Tumor
Adenoma, Islet Cell
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Adenoma
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on April 21, 2017