Efficacy and Safety of Nilotinib (AMN107) Compared With Current Treatment Options in Patients With GIST Who Have Failed Both Imatinib and Sunitinib

Gastrointestinal Stromal Tumors Clinical Trial

— ENEST  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00471328
• Other study ID #: CAMN107A2201
• Secondary ID: 2006-002267-11
• Status: Completed
• Phase: Phase 3
• First received: April 26, 2007
• Last updated: June 5, 2012
• Start date: March 2007
• Est. completion date: June 2011

Study information

• Verified date: June 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentCzech Republic: State Institute for Drug ControlCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesSouth Korea: Korea Food and Drug Administration (KFDA)Italy: The Italian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSpain: Ministry of Health and ConsumptionSwitzerland: SwissmedicTaiwan: Department of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The study evaluated the safety and efficacy of nilotinib versus current treatment in adults with gastrointestinal stromal tumors (GIST) who have either progressed or who were intolerant to the first and second line treatments.

Other known NCT identifiers

• NCT00488150

Recruitment information / eligibility

• Status: Completed
• Enrollment: 248
• Est. completion date: June 2011
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Gastrointestinal Stromal Tumors

Intervention

Drug:
• Nilotinib
Nilotinib 400 mg twice daily (bid)

Other:
• Best Supportive Care (BSC) +/- imatinib or sunitinib
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.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Auchenflower	Queensland
Australia	Novartis Investigative Site	East Melbourne	Victoria
Austria	Novartis Investigative Site	Vienna
Canada	Novartis Investigative Site	Toronto
Czech Republic	Novartis Investigative Site	Praha 5
France	Novartis Investigative Site	Bordeaux
France	Novartis Investigative Site	Lyon
France	Novartis Investigative Site	Marseille
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Duesseldorf
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Koln
Germany	Novartis Investigative Site	Mannheim
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Tubingen
Italy	Novrtis Investigative Site	Bologna
Italy	Novartis Investigative Site	Milan
Korea, Republic of	Novartis Investigative Site	Seoul
Netherlands	Novartis Investigative Site	Leiden
Poland	Novartis Investigative Site	Warszawa
Spain	Novartis Investigative Site	Madrid
Switzerland	Novartis Investigative Site	Chur
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago Hospital	Chicago	Illinois
United States	Wayne State University/Wertz Clinical Cancer Center	Detroit	Michigan
United States	University of Texas/MD Anderson Cancer Center	Houston	Texas
United States	UCLA's Jonsson Comprehensive Cancer Center	Los Angeles	California
United States	St. Vincent's Comprehensive Cancer Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	Washington University School of Medicine - Siteman Cancer Center	St. Louis	Missouri
United States	H. Lee Moffitt Cancer Center	Tampa	Florida
United States	Washington Hospital Center - Washington Cancer Institute	Washington	District of Columbia
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Czech Republic,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)	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.	Up to 16 months	No
Primary	Progression-free Survival (PFS) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set	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.	Up to 34 months	No
Secondary	Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)	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.	Up to 16 months	No
Secondary	Overall Survival During Core and Extension Phases of the Study	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.	Up to 50 months (including core, extension and follow up period)	No
Secondary	Overall Survival for Treatment Crossover Analysis Set	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.	Up to 34 months	No
Secondary	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)	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).	Up to 16 months	No
Secondary	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	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).	Up to 34 months	No
Secondary	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)	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.	Up to 16 months	No
Secondary	Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set	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.	Up to 34 months	No