Clinical trial NCT00237185: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumor (GIST)
Keywords: GIST
c-kit
imatinib mesylate
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2005-10-12
Enrollment: 148
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: 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.


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.

Primary outcomes:
measure: Best Tumor Response (Core)
timeFrame: Month 36
measure: Best Tumor Response (Core + Extension)
timeFrame: Month 156
Secondary outcomes:
measure: Overall Survival (Core)
timeFrame: Date of first imatinib dose to the date of death during the core period, up to 36 months.
measure: Overall Survival (Core + Extension)
timeFrame: Date of first imatinib dose to the date of death during the core and extension periods, up to 156 months.
measure: Duration of Response (Core)
timeFrame: Date of confirmed best PR or CR to date of confirmed disease progression during the core period, up to 36 months.
measure: Duration of Response (Core + Extension)
timeFrame: Date of confirmed best PR or CR to date of confirmed disease progression during the core and extension periods, up to 156 months
measure: Progression Free Survival (PFS) (Core + Extension)
timeFrame: 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.
measure: Time to Treatment Failure (Core)
timeFrame: 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.
measure: Time to Treatment Failure (Core + Extension)
timeFrame: 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.
measure: Time to Onset of Response (Core)
timeFrame: 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.
measure: Time to Onset of Response (Core + Extension)
timeFrame: 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.
measure: Time to Progression (Core + Extension)
timeFrame: 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.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute Dept of Sarcoma Oncology
state: Massachusetts
city: Portland
country: United States
facility: Oregon Health Sciences University Dept. of Oregon Health Sci.
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Geelong
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Helsinki
country: Finland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Novartis
name: Novartis
role: STUDY_CHAIR
References: