Clinical trial NCT00293124: Open-label Trial of GlivecWith Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumors
Official title: An Open-label Trial of Glivec in Patients With Unresectable or Metastatic Malignant Gastrointestinal Stromal Tumors Expressing C-kit.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastrointestinal Stromal Tumors
Keywords: Gastrointestinal Stromal Tumors
Glivec
Lead sponsor: Central European Cooperative Oncology Group
Sponsor class: OTHER
First posted: 2006-02-17
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The rationale is to assess the clinical and biological activity of Imatinib and to compare the data with historic data.

Additionally this study has been designed to gain more experience with the treatment of GIST in several Central and Eastern European Countries.

Detailed description: This is a multicenter open label clinical trial to be performed in patients with incurable malignant GISTs that are unresectable or metastatic. Approximately 150 patients will enter the trial.

Patients will receive Imatinib 400 mg p.o./day for a period of up to 24 months provided that in the opinion of the investigator the patient is benefiting from treatment with Imatinib, and in the absence of any safety concerns.

Treatment after completion of the 24 months study is at the discretion of the investigator. Imatinib should be increased to 600 mg p.o./day and then to 400 mg b.i.d if the patient is progressing on the respective dose level.

Eligibility criteria: Inclusion Criteria:

* Patients \>= 18 years of age
* Histologically documented diagnosis of GIST which is malignant as well as unresectable (=not amenable to surgery with curative intent) and/or metastatic and therefore incurable Immunohistochemical documentation of c-kit (CD117) expression by tumor
* At least one measurable site of disease (as defined by Southwestern Oncology Group Solid Tumor Response Criteria) which has not been previously embolised or irradiated
* Performance status 0,1, 2 or 3 (ECOG)
* Adequate end organ function, defined as the following: total bilirubin \< 1.5 x ULN, SGOT and SGPT \< 2.5 x UNL (or \< 5 x ULN if hepatic metastases are present), creatinine \< 1.5 x ULN, ANC \> 1.5 x 109/L, platelets \> 100 x 109/L
* Female patients of child-bearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug
* Life expectancy of at least 6 months
* Written, voluntary, informed consent
* Patients who were previously treated with chemotherapy will be eligible for this study
* Patient who are at least 5 years free of melanoma will be eligible for this study

Exclusion Criteria:

* Patient has received any other investigational agents within 28 days of first day of study drug dosing
* Patient is \< 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention and CECOGs' approval is obtained, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed
* Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
* Female patients who are pregnant or breast-feeding.
* Patient has a severe and/or uncontrolled medical disease (i.e., uncontrolled diabetes, chronic renal disease, or active uncontrolled infection)
* Patient has a known brain metastasis
* Patient has an acute or known chronic liver disease (i.e., chronic active hepatitis, cirrhosis)
* Patient has a known diagnosis of human immunodeficiency virus (HIV) infection
* Patient received chemotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin-C) prior to study entry
* Patient previously received radiotherapy to \>= 25 % of the bone marrow
* Patient had a major surgery within 2 weeks prior to study entry
* Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent
* Therapeutic anticoagulation with warfarin (e.g. Coumadin® or Coumadine®)

Primary outcomes:
measure: Time to Disease Progression
timeFrame: until PD
Secondary outcomes:
measure: Time to Disease Progression
timeFrame: until PD
measure: Overall Survival
timeFrame: until death
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: AKH, Universitätsklinik für Innere Medizin 1
city: Sarajevo
country: Bosnia and Herzegovina
facility: Institute of Oncology Sarajevo
city: Sofia
country: Bulgaria
facility: SBALO National Oncology Center
city: Sofia
country: Bulgaria
facility: National Oncological Center Hospital
city: Sofia
country: Bulgaria
facility: Sofia Cancer Center compl. Mladost ,
city: Split
country: Croatia
facility: Clinical Hospital Split, Center of Oncology
city: Zagreb
country: Croatia
facility: University Hospital Rebro
city: Prague
country: Czech Republic
facility: FN Bulovka
city: Prague
country: Czech Republic
facility: Radioterapeticko-onkologicke. Oddeleni FN Motol
city: Vilnius
country: Lithuania
facility: Lithuanian Oncology Center,
city: Bucuresti
country: Romania
facility: Institutul Oncologic Bucuresti
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic Cluj
city: Craiova
country: Romania
facility: Emergency Clinical County Hospital , Clin Oncol. Dep
city: Beograd
country: Serbia
facility: Institut za onkologiju i
city: Bratislava
country: Slovakia
facility: National Institute of Oncology
city: Ljubljana
country: Slovenia
facility: Oncology Institute Ljubljana
Study officials:
affiliation: University Clinic of Internal Medicine I / Clinical Oncology
name: Thomas Brodowicz, MD
role: PRINCIPAL_INVESTIGATOR
References: