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

Phase 3

Completed

Conditions: Gastrointestinal Stromal Tumors

Interventions: Drug: Nilotinib
Other: Best Supportive Care (BSC) +/- imatinib or sunitinib

Registration Number: NCT00471328

Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 248

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nilotinib	Nilotinib	400mg twice daily in core and extension phases of the study.
Control/cross-over to Nilotinib	Best Supportive Care (BSC) +/- imatinib or sunitinib	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.
Control/cross-over to Nilotinib	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.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS) From Central Radiology Review Based on Primary Analysis (Data Cut-off: June, 2008)	Up to 16 months	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.
Progression-free Survival (PFS) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set	Up to 34 months	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.

Secondary Outcome Measures

Name	Time	Method
Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)	Up to 16 months	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.
Overall Survival During Core and Extension Phases of the Study	Up to 50 months (including core, extension and follow up period)	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.
Overall Survival for Treatment Crossover Analysis Set	Up to 34 months	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.
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)	Up to 16 months	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).
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	Up to 34 months	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).
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)	Up to 16 months	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.
Overall Clinical Benefit (Complete Response [CR]/Partial Response [PR] or Stable Disease [SD]) From Local Investigator's Assessment Based on Treatment Crossover Analysis Set	Up to 34 months	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.

Trial Locations

Locations (13): Washington University School of Medicine - Siteman Cancer Center
🇺🇸
St. Louis, Missouri, United States
Dana Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
University of Texas/MD Anderson Cancer Center
🇺🇸
Houston, Texas, United States
UCLA's Jonsson Comprehensive Cancer Center
🇺🇸
Los Angeles, California, United States
Washington Hospital Center - Washington Cancer Institute
🇺🇸
Washington, District of Columbia, United States
Novartis Investigative Site
🇨🇭
Chur, Switzerland
Wayne State University/Wertz Clinical Cancer Center
🇺🇸
Detroit, Michigan, United States
University of Chicago Hospital
🇺🇸
Chicago, Illinois, United States
Fox Chase Cancer Center
🇺🇸
Philadelphia, Pennsylvania, United States
St. Vincent's Comprehensive Cancer Center
🇺🇸
New York, New York, United States
H. Lee Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Novrtis Investigative Site
🇮🇹
Bologna, Italy
Wake Forest University Health Sciences
🇺🇸
Winston-Salem, North Carolina, United States