Back to resultsA Study of the Efficacy and Safety of Imatinib Mesylate in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Gene
Primary Purpose
Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumor (GIST)
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Imatinib mesylate
Sponsored by
About this trial
This is an interventional treatment trial for Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumor (GIST) focused on measuring GIST, c-kit, imatinib mesylate
Eligibility Criteria
Inclusion Criteria: Men and non-pregnant women ≥18 years of age with the histopathologically documented diagnosis of malignant GIST that was unresectable and/or metastatic. Confirmation of KIT (CD117) expression via immunohistochemical analysis of tumor sample was also required At least one measurable lesion, as defined by Southwestern Oncology Group (SWOG) Solid Tumor Response Criteria, which had not been previously embolized or irradiated Performance status ≤3 as defined by the Eastern Cooperative Oncology Group (ECOG) criteria, as well as a life expectancy ≥6 months and adequate end organ function defined as follows: Total bilirubin <1.5 times upper limit of normal (ULN), aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) <2.5 x ULN (or <5 x ULN if hepatic metastases were present), creatinine <1.5 x ULN, absolute neutrophil count (ANC) >1.5 x 10^9/L, platelet count >100 x 10^9/L Exclusion Criteria: Patients with fewer than five years of disease-free survival from any other (non-GIST) malignancy except if the other malignancy was not currently clinically significant and did not require active intervention or if the other malignancy was a basal cell skin cancer or a cervical carcinoma in situ Patients with known brain metastases Evidence of any of the following disorders: Grade III/IV cardiac failure as defined by the New York Heart Association Criteria, severe concomitant disease, acute or known chronic liver disease (i.e. chronic active hepatitis, cirrhosis) or HIV infection Chemotherapy or other investigational therapy within four weeks prior to study entry (six weeks for nitrosourea or mitomycin-C) and/or radiotherapy to ≥25% of the bone marrow Inability to cooperate Major surgery within two weeks or exposure to other investigational agents within 28 days of entry into the study Other protocol-defined inclusion / exclusion criteria may have applied.
Sites / Locations
- Dana Farber Cancer Institute Dept of Sarcoma Oncology
- Oregon Health Sciences University Dept. of Oregon Health Sci.
- Fox Chase Cancer Center
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
imatinib mesylate 400 mg
imatinib mesylate 600 mg
Arm Description
400 mg once daily
600 mg once daily
Outcomes
Primary Outcome Measures
Best Tumor Response (Core)
Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.
Best Tumor Response (Core + Extension)
Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.
Secondary Outcome Measures
Overall Survival (Core)
Overall survival was analyzed as time to event for all participants. Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.
Overall Survival (Core + Extension)
Overall survival was analyzed as time to event for all participants. Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.
Duration of Response (Core)
Duration of response was analyzed as time to event for all participants whose best response was at least a PR. The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response. The end of response was the first tumor assessment noting PD.
Duration of Response (Core + Extension)
Duration of response was analyzed as time to event for all participants whose best response was at least a PR. The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response. The end of response was the first tumor assessment noting PD.
Progression Free Survival (PFS) (Core + Extension)
Progression free survival was analyzed as a time to event for each participant. If a participant had no event, then the PFS was censored at the last tumor assessment.
Time to Treatment Failure (Core)
Time to treatment failure was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis ate the time of their last tumor assessment.
Time to Treatment Failure (Core + Extension)
Time to treatment failure was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.
Time to Onset of Response (Core)
Time to response was analyzed as time to event for all participants. Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.
Time to Onset of Response (Core + Extension)
Time to response was analyzed as time to event for all participants. Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.
Time to Progression (Core + Extension)
Time to progression was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.
Full Information
NCT ID
NCT00237185
First Posted
October 9, 2005
Last Updated
August 14, 2014
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00237185
Brief Title
A Study of the Efficacy and Safety of Imatinib Mesylate in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Gene
Official Title
Open, Randomized, Phase II Study of Glivec in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Plus 10 Year Extension Study
Study Type
Interventional
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
June 2000 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
In the core study, participants with unresectable or metastatic gastrointestinal stromal tumors expressing c-kit were treated with either 400 mg or 600 mg imatinib mesylate for 3 years. The 10 year extension study allowed participants, who successfully completed the core study, to continue study treatment with imatinib mesylate provided they still benefited from treatment and did not demonstrate safety concerns as per the investigator's opinion.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumor (GIST)
Keywords
GIST, c-kit, imatinib mesylate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
148 (Actual)
8. Arms, Groups, and Interventions
Arm Title
imatinib mesylate 400 mg
Arm Type
Experimental
Arm Description
400 mg once daily
Arm Title
imatinib mesylate 600 mg
Arm Type
Experimental
Arm Description
600 mg once daily
Intervention Type
Drug
Intervention Name(s)
Imatinib mesylate
Other Intervention Name(s)
Glivec, Gleevec
Intervention Description
Participants were randomized 1:1 to receive imatinib mesylate 400 mg/day or 600 mg/day. Upon unsatisfactory treatment effect on the starting dose of 400 mg/day or 600 mg/day imatinib mesylate, in the opinion of the treating physician, a dose increase up to 600 mg/day or 800 mg/day, was allowed provided that the participant continued to benefit from the treatment and in the absence of safety concerns.
Primary Outcome Measure Information:
Title
Best Tumor Response (Core)
Description
Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.
Time Frame
Month 36
Title
Best Tumor Response (Core + Extension)
Description
Best tumor response was based on the Southwestern Oncology Group (SWOG) criteria. Objective tumor response assessments were categorized according to the following criteria: complete response (CR), partial response (PR), no change or stable disease (SD), progression of disease (PD), unknown where the progression has not been documented and one or more measurable or evaluable sites have not been assessed (UNK), status after resection for progression (RP), status after resection for safety (RS), status after preventive resection (RPR), progressive after first resection (PDR) and not evaluable. Any tumor assessment after surgical resection for preventative reasons was treated like tumor assessments of UNK for calculation of best response. Tumor assessments with current objective status = RP, RS or PDR were treated like assessments with objective tumor status = PD n the calculation of best response.
Time Frame
Month 156
Secondary Outcome Measure Information:
Title
Overall Survival (Core)
Description
Overall survival was analyzed as time to event for all participants. Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.
Time Frame
Date of first imatinib dose to the date of death during the core period, up to 36 months.
Title
Overall Survival (Core + Extension)
Description
Overall survival was analyzed as time to event for all participants. Participants who did not die were censored at the last date known alive, which is the last date of any study medication, laboratory sample, tumor assessment, adverse event end date or date of last contact.
Time Frame
Date of first imatinib dose to the date of death during the core and extension periods, up to 156 months.
Title
Duration of Response (Core)
Description
Duration of response was analyzed as time to event for all participants whose best response was at least a PR. The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response. The end of response was the first tumor assessment noting PD.
Time Frame
Date of confirmed best PR or CR to date of confirmed disease progression during the core period, up to 36 months.
Title
Duration of Response (Core + Extension)
Description
Duration of response was analyzed as time to event for all participants whose best response was at least a PR. The onset of response was the first tumor assessment that was subsequently confirmed to constitute at least a partial best response. The end of response was the first tumor assessment noting PD.
Time Frame
Date of confirmed best PR or CR to date of confirmed disease progression during the core and extension periods, up to 156 months
Title
Progression Free Survival (PFS) (Core + Extension)
Description
Progression free survival was analyzed as a time to event for each participant. If a participant had no event, then the PFS was censored at the last tumor assessment.
Time Frame
Date of first imatinib dose to earliest date of progression, resection due to safety/progression, death due to any cause or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.
Title
Time to Treatment Failure (Core)
Description
Time to treatment failure was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis ate the time of their last tumor assessment.
Time Frame
Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core period, up to 36 months.
Title
Time to Treatment Failure (Core + Extension)
Description
Time to treatment failure was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.
Time Frame
Date of first imatinib dose to date of earliest occurrence of progression, death due to any cause, or discontinuation from the trial for any reason other than the condition no longer required therapy during the core and extension periods, up to 156 month.
Title
Time to Onset of Response (Core)
Description
Time to response was analyzed as time to event for all participants. Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.
Time Frame
Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core period, up to 36 months.
Title
Time to Onset of Response (Core + Extension)
Description
Time to response was analyzed as time to event for all participants. Participants who did not meet the definition of confirmed PR/CR were censored at the time of their last progression-free tumor assessment.
Time Frame
Date of first imatinib dose to the date of the first tumor assessment that was later confirmed to be at least a partial response during the core and extension periods, up to 156 months.
Title
Time to Progression (Core + Extension)
Description
Time to progression was analyzed as time to event for all participants. Participants who had neither progressed, died nor discontinued from the trial for any reason other than the condition no longer required therapy were censored for analysis at the time of their last tumor assessment.
Time Frame
Date of first imatinib dose to date of progression or death due to disease indication or discontinuation due to unsatisfactory therapeutic effect during the core and extension periods, up to 156 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men and non-pregnant women ≥18 years of age with the histopathologically documented diagnosis of malignant GIST that was unresectable and/or metastatic. Confirmation of KIT (CD117) expression via immunohistochemical analysis of tumor sample was also required
At least one measurable lesion, as defined by Southwestern Oncology Group (SWOG) Solid Tumor Response Criteria, which had not been previously embolized or irradiated
Performance status ≤3 as defined by the Eastern Cooperative Oncology Group (ECOG) criteria, as well as a life expectancy ≥6 months and adequate end organ function defined as follows: Total bilirubin <1.5 times upper limit of normal (ULN), aspartate aminotransferase (SGOT) and alanine aminotransferase (SGPT) <2.5 x ULN (or <5 x ULN if hepatic metastases were present), creatinine <1.5 x ULN, absolute neutrophil count (ANC) >1.5 x 10^9/L, platelet count >100 x 10^9/L
Exclusion Criteria:
Patients with fewer than five years of disease-free survival from any other (non-GIST) malignancy except if the other malignancy was not currently clinically significant and did not require active intervention or if the other malignancy was a basal cell skin cancer or a cervical carcinoma in situ
Patients with known brain metastases
Evidence of any of the following disorders: Grade III/IV cardiac failure as defined by the New York Heart Association Criteria, severe concomitant disease, acute or known chronic liver disease (i.e. chronic active hepatitis, cirrhosis) or HIV infection
Chemotherapy or other investigational therapy within four weeks prior to study entry (six weeks for nitrosourea or mitomycin-C) and/or radiotherapy to ≥25% of the bone marrow
Inability to cooperate
Major surgery within two weeks or exposure to other investigational agents within 28 days of entry into the study
Other protocol-defined inclusion / exclusion criteria may have applied.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Novartis
Organizational Affiliation
Novartis
Official's Role
Study Chair
Facility Information:
Facility Name
Dana Farber Cancer Institute Dept of Sarcoma Oncology
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Oregon Health Sciences University Dept. of Oregon Health Sci.
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Novartis Investigative Site
City
Geelong
State/Province
Victoria
ZIP/Postal Code
3220
Country
Australia
Facility Name
Novartis Investigative Site
City
Helsinki
ZIP/Postal Code
FIN-00029
Country
Finland
12. IPD Sharing Statement
Learn more about this trial
A Study of the Efficacy and Safety of Imatinib Mesylate in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Gene
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