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

Novartis Pharmaceuticals248 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

248

Conditions

Gastrointestinal Stromal Tumors

Interventions

NilotinibDRUG

Nilotinib 400 mg twice daily (bid)

Best Supportive Care (BSC) +/- imatinib or sunitinibOTHER

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (35)

Outcomes

Primary Outcomes

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.

Time frame: Up to 16 months

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.

Time frame: Up to 34 months

Secondary Outcomes

Overall Survival Based on Primary Analysis (Data Cut-off:June, 2008)

Time frame: Up to 16 months

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.

Data from ClinicalTrials.gov

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UCLA's Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Washington Hospital Center - Washington Cancer Institute

Washington D.C., District of Columbia, United States

H. Lee Moffitt Cancer Center

Tampa, Florida, United States

University of Chicago Hospital

Chicago, Illinois, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Wayne State University/Wertz Clinical Cancer Center

Detroit, Michigan, United States

Washington University School of Medicine - Siteman Cancer Center

St Louis, Missouri, United States

St. Vincent's Comprehensive Cancer Center

New York, New York, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

...and 25 more locations

Time frame: Up to 50 months (including core, extension and follow up period)

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.

Time frame: Up to 34 months

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).

Time frame: Up to 16 months

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).

Time frame: Up to 34 months

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.

Time frame: Up to 16 months

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