- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00471328
Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib (ENEST)
A Randomized, Open-label, Multi-center Study to Evaluate the Efficacy of Nilotinib Versus Best Supportive Care With or Without a Tyrosine Kinase Inhibitor (Investigator's Choice) in Adult Patients With Gastrointestinal Stromal Tumors Resistant to Both Imatinib and Sunitinib
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Queensland
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Auchenflower, Queensland, Australia, 4066
- Novartis Investigative Site
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Victoria
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East Melbourne, Victoria, Australia, 3002
- Novartis Investigative Site
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Vienna, Austria
- Novartis Investigative Site
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Toronto, Canada
- Novartis Investigative Site
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Praha 5, Czech Republic
- Novartis Investigative Site
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Bordeaux, France
- Novartis Investigative Site
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Lyon, France
- Novartis Investigative Site
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Marseille, France
- Novartis Investigative Site
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Berlin, Germany
- Novartis Investigative Site
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Duesseldorf, Germany
- Novartis Investigative Site
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Essen, Germany
- Novartis Investigative Site
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Frankfurt, Germany
- Novartis Investigative Site
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Hannover, Germany
- Novartis Investigative Site
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Koln, Germany
- Novartis Investigative Site
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Mannheim, Germany
- Novartis Investigative Site
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Muenchen, Germany
- Novartis Investigative Site
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Tubingen, Germany
- Novartis Investigative Site
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Bologna, Italy
- Novrtis Investigative Site
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Milan, Italy
- Novartis Investigative Site
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Seoul, Korea, Republic of
- Novartis Investigative Site
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Leiden, Netherlands
- Novartis Investigative Site
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Warszawa, Poland
- Novartis Investigative Site
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Madrid, Spain
- Novartis Investigative Site
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Chur, Switzerland
- Novartis Investigative Site
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California
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Los Angeles, California, United States, 90095
- UCLA's Jonsson Comprehensive Cancer Center
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District of Columbia
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Washington, District of Columbia, United States, 20010-2965
- Washington Hospital Center - Washington Cancer Institute
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Florida
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Tampa, Florida, United States, 33612
- H. Lee Moffitt Cancer Center
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Illinois
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Chicago, Illinois, United States, 60637
- University of Chicago Hospital
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Dana Farber Cancer Institute
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Michigan
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Detroit, Michigan, United States, 48201
- Wayne State University/Wertz Clinical Cancer Center
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Missouri
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St. Louis, Missouri, United States, 63110
- Washington University School of Medicine - Siteman Cancer Center
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New York
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New York, New York, United States, 10011
- St. Vincent's Comprehensive Cancer Center
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North Carolina
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Winston-Salem, North Carolina, United States, 27157-1082
- Wake Forest University Health Sciences
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19111-2497
- Fox Chase Cancer Center
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Texas
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Houston, Texas, United States, 77030-4009
- University of Texas/MD Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion criteria (Core Phase):
- Age ≥18 years
- Radiological confirmation of disease progression during imatinib and sunitinib therapy OR intolerance to imatinib and/or sunitinib
- At least one measurable site of disease on CT/MRI scan
- Physically fit even if not able to work
- Normal organ, electrolyte, and bone marrow function
Inclusion criteria (Extension Phase):
- Patients whose tumors had progressed on the control arm and had crossed over to the nilotinib arm.
- The study was stopped due to meeting the primary efficacy endpoint of PFS at the interim analysis.
- Patients who were still being treated at the close of the Core study on the control arm or nilotinib arm (whose tumors have not progressed at the time of the end of the Core study).
- Patients must have had documented, confirmed stable, partial or complete response as defined by the RECIST criteria at the time of entry into the Extension study with the exception of patients who had progressed on the control arm.
Exclusion criteria (Core Phase):
- Previous treatment with nilotinib or any other drug in this class or other targeted therapy
- Treatment with any cytotoxic and/or investigational cytotoxic drug ≤ 4 weeks prior to study entry
- Impaired cardiac function
- Use of coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon)
- Women who are pregnant or lactating
Exclusion criteria (Extension Phase):
- Use of other anticancer treatments or investigational drugs (with exception of the study drugs)
- Patients with a history of noncompliance with study drug treatment in the Core study protocol.
Other protocol-defined inclusion/exclusion criteria applied
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Nilotinib
400mg twice daily in core and extension phases of the study.
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Nilotinib 400 mg twice daily (bid)
Other Names:
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Active Comparator: Control/cross-over to Nilotinib
In core study phase, patients in this arm received Best Supportive Care (BSC) with or without imatinib or sunitinib at the last tolerated dose or at the investigator's choice until documented disease progression followed by cross-over to nilotinib arm. Patients entering the extension study on this control arm were permitted to cross over to nilotinib arm only upon documented disease progression. |
Nilotinib 400 mg twice daily (bid)
Other Names:
Can include pain medication, localized radiotherapy, nutritional support, and/or oxygen therapy and blood transfusions.
Imatinib or sunitinib can be administered at the last tolerated dose and regimen or at the Investigator's choice.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Progression-free Survival (PFS) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)
Time Frame: Up to 16 months
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Progression-free survival (PFS) is the time from date of randomization to the date of first documented progression or death due to any cause.
If a participant has not had an event, progression-free survival is censored at the time of last adequate tumor assessment.
Progression is defined according to Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.
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Up to 16 months
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Progression-free Survival (PFS) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
Time Frame: Up to 34 months
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PFS is defined as the time from the first date of cross-over to nilotinib therapy from the control arm to the date of the first observation of documented disease progression.
Tumor assessment was based on the local investigator's measurement using Modified Response Evaluation Criteria in Solid Tumors (modified RECIST) criteria.
Progression is defined according to modified RECIST criteria as at least a 20% increase in the sum of the longest diameter of target lesions, worsening of the non-target lesions or the appearance of one or more new lesions.
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Up to 34 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)
Time Frame: Up to 16 months
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Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause.
If a participant is not known to have died, survival will be censored at the date of last contact.
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Up to 16 months
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Overall Survival During Core and Extension Phases of the Study
Time Frame: Up to 50 months (including core, extension and follow up period)
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Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause.
If a participant is not known to have died, survival will be censored at the date of last contact.
This analysis included both Core and Extension data as well as survival follow up data.
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Up to 50 months (including core, extension and follow up period)
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Overall Survival for Treatment Crossover Analysis Set
Time Frame: Up to 34 months
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For patients who crossed-over to nilotinib from the control arm, the overall survival was the time from the first dose date of nilotinib after switching from control arm to the date of death due to any cause.
If death was not observed, the OS was censored at the latest date the patient was known to be alive.
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Up to 34 months
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Number of Responders With Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) From Central Radiology Review During Primary Analysis (Data Cut-off: June, 2008)
Time Frame: Up to 16 months
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The best overall response is the best response recorded from randomization until disease progression.
The CR/PR must be confirmed by at least two determinations at least 4 weeks apart before progression.
Using modified RECIST criteria, a Complete Response is defined as disappearance of all lesions, and a Partial Response is defined as either 1) at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions or progression of non-target lesions or 2) disappearance of all target lesions but persistence of one or more non-target lesion(s).
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Up to 16 months
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Number of Responders With Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
Time Frame: Up to 34 months
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The best overall response (CR/PR) must be confirmed by at least two determinations at least 4 weeks apart before progression.
Using modified RECIST criteria, a Complete Response is defined as disappearance of all lesions, and a Partial Response is defined as either 1) at least a 30% decrease in the sum of the longest diameter of target lesions and no new lesions or progression of non-target lesions or 2) disappearance of all target lesions but persistence of one or more non-target lesion(s).
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Up to 34 months
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Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)
Time Frame: Up to 16 months
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The overall clinical benefit includes the best overall responses of CR, PR, or SD.
The best overall responses of CR/PR must be confirmed by at least two determinations at least 4 weeks apart before progression.
The best overall response of SD must have at least one SD (or better) at least 6 weeks (or 6 months or 12 months as applicable) after randomization but before progression.
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Up to 16 months
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Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
Time Frame: Up to 34 months
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The overall clinical benefit includes the best overall responses of CR, PR, or SD.
The best overall responses of CR/PR must be confirmed by at least two determinations at least 4 weeks apart before progression.
The best overall response of SD must have at least one SD (or better) at least 6 weeks (or 6 months or 12 months as applicable) after randomization but before progression.
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Up to 34 months
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Neoplasms, Connective Tissue
- Gastrointestinal Stromal Tumors
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Protein Kinase Inhibitors
- Sunitinib
- Imatinib Mesylate
Other Study ID Numbers
- CAMN107A2201
- 2006-002267-11 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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