A Study of the Efficacy and Safety of Imatinib Mesylate in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors Expressing C-kit Gene

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00237185
First received: October 9, 2005
Last updated: June 13, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumor (GIST)
Drug: Imatinib mesylate
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Best Tumor Response (Core) [ Time Frame: Month 36 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Month 156 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Date of first imatinib dose to the date of death ] [ Designated as safety issue: No ]
    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) [ Time Frame: Date of first imatinib dose to the date of death ] [ Designated as safety issue: No ]
    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) [ Time Frame: Date of confirmed best PR or CR to date of confirmed disease progression ] [ Designated as safety issue: No ]
    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) [ Time Frame: Date of confirmed best PR or CR to date of confirmed disease progression ] [ Designated as safety issue: No ]
    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) [ 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. ] [ Designated as safety issue: No ]
    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 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. ] [ Designated as safety issue: No ]
    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 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. ] [ Designated as safety issue: No ]
    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 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 ] [ Designated as safety issue: No ]
    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 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 ] [ Designated as safety issue: No ]
    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 Frame: Date of first imatinib dose to date of the earliest tumor assessment date of progression or resection due to safety/progression, or progression after resection, death due to disease indication or discontinuation due to unsatisfactory therapeutic effect. ] [ Designated as safety issue: No ]
    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.


Enrollment: 148
Study Start Date: June 2000
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: imatinib mesylate 400 mg
400 mg once daily
Drug: Imatinib mesylate
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.
Other Name: Glivec, Gleevec
Experimental: imatinib mesylate 600 mg
600 mg once daily
Drug: Imatinib mesylate
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.
Other Name: Glivec, Gleevec

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00237185

Locations
United States, Massachusetts
Dana Farber Cancer Institute Dept of Sarcoma Oncology
Boston, Massachusetts, United States, 02115
United States, Oregon
Oregon Health Sciences University Dept. of Oregon Health Sci.
Portland, Oregon, United States, 97201
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
Australia, Victoria
Novartis Investigative Site
Geelong, Victoria, Australia, 3220
Finland
Novartis Investigative Site
Helsinki, Finland, FIN-00029
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Study Chair: Novartis Novartis
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00237185     History of Changes
Other Study ID Numbers: CSTI571B2222, CSTI571B2222/E1
Study First Received: October 9, 2005
Results First Received: June 13, 2014
Last Updated: June 13, 2014
Health Authority: United States: Food and Drug Administration
Finland: Finnish Medicines Agency

Keywords provided by Novartis:
GIST
c-kit
imatinib mesylate

Additional relevant MeSH terms:
Gastrointestinal Stromal Tumors
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Imatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014