Trial record 1 of 87 for:
cooperate 2
Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET (COOPERATE-2)
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| ClinicalTrials.gov Identifier: NCT01374451 |
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Recruitment Status :
Terminated
(The study was stopped for not meeting the primary endpoint for PFS.)
First Posted : June 16, 2011
Results First Posted : December 20, 2016
Last Update Posted : December 20, 2016
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Sponsor:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Islet Cell Tumor | Drug: Everolimus Drug: Pasireotide LAR | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 160 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (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 |
| Study Start Date : | June 2011 |
| Actual Primary Completion Date : | February 2015 |
| Actual Study Completion Date : | February 2015 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Paseriotide LAR + Everolimus
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
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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 |
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Experimental: Everolimus
everolimus 10 mg once daily po alone
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Drug: Everolimus
Everolimus was supplied as tablets of 5 mg strength, blister-packed under aluminum foil in units of 10 tablets
Other Name: RAD001 |
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 ]
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| 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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01374451
Locations
Show 47 study locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
| Responsible Party: | Novartis Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01374451 |
| Other Study ID Numbers: |
CSOM230I2201 2010-023183-40 ( EudraCT Number ) |
| First Posted: | June 16, 2011 Key Record Dates |
| Results First Posted: | December 20, 2016 |
| Last Update Posted: | December 20, 2016 |
| Last Verified: | October 2016 |
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
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Pancreatic Neuroendocrine tumors PNET |
Pasireotide Everolimus Advanced progressive pancreatic neuroendocrine tumor |
Additional relevant MeSH terms:
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Neuroendocrine Tumors Adenoma, Islet Cell Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Adenoma Neoplasms, Glandular and Epithelial Pancreatic Neoplasms Digestive System Neoplasms Neoplasms by Site Endocrine Gland Neoplasms Digestive System Diseases |
Pancreatic Diseases Endocrine System Diseases Everolimus Pasireotide MTOR Inhibitors Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antineoplastic Agents Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |