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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastrointestinal Stromal Tumors
Keywords: GIST
adults
imatinib resistant
sunitinib resistant
AMN107
nilotinib
treatment
Gastrointestinal stromal tumor (GIST)
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2007-05-09
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Progression-free Survival (PFS) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)
timeFrame: Up to 16 months
measure: Progression-free Survival (PFS) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
timeFrame: Up to 34 months
Secondary outcomes:
measure: Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)
timeFrame: Up to 16 months
measure: Overall Survival During Core and Extension Phases of the Study
timeFrame: Up to 50 months (including core, extension and follow up period)
measure: Overall Survival for Treatment Crossover Analysis Set
timeFrame: Up to 34 months
measure: 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)
timeFrame: Up to 16 months
measure: 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
timeFrame: Up to 34 months
measure: 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)
timeFrame: Up to 16 months
measure: Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set
timeFrame: Up to 34 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA's Jonsson Comprehensive Cancer Center
state: California
city: Washington
country: United States
facility: Washington Hospital Center - Washington Cancer Institute
state: District of Columbia
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago Hospital
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University/Wertz Clinical Cancer Center
state: Michigan
city: St. Louis
country: United States
facility: Washington University School of Medicine - Siteman Cancer Center
state: Missouri
city: New York
country: United States
facility: St. Vincent's Comprehensive Cancer Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas/MD Anderson Cancer Center
state: Texas
city: Auchenflower
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: East Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
city: Praha 5
country: Czech Republic
facility: Novartis Investigative Site
city: Bordeaux
country: France
facility: Novartis Investigative Site
city: Lyon
country: France
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Duesseldorf
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Koln
country: Germany
facility: Novartis Investigative Site
city: Mannheim
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Tubingen
country: Germany
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novrtis Investigative Site
city: Milan
country: Italy
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Leiden
country: Netherlands
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Chur
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: