Imatinib Mesylate in Treating Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumor

European Organisation for Research and Treatment of Cancer (EORTC)

Status and phase

Unknown

Phase 3

Conditions

Gastrointestinal Stromal Tumor

Treatments

Drug: imatinib mesylate

Study type

Interventional

Funder types

Other

NETWORK

Identifiers

NCT00685828

AGITG-AGO102-GIST

ISG-62005

EORTC-62005

SSG-15

Details and patient eligibility

About

RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known which dose of imatinib mesylate is more effective in treating gastrointestinal stromal tumor.

PURPOSE: This randomized phase III trial is studying two different doses of imatinib mesylate to compare how well they work in treating patients with unresectable or metastatic gastrointestinal stromal tumor.

Full description

OBJECTIVES:

Primary

To compare outcomes of patients with unresectable or metastatic gastrointestinal stromal tumor that expresses KIT (CD117) treated with low-dose imatinib mesylate vs high-dose imatinib mesylate.

Secondary

To assess response rates in patients treated with two different doses of imatinib mesylate.
To assess the toxicities of two different doses of imatinib mesylate in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, measurability of disease (measurable vs non-measurable), and WHO performance status (0-2 vs 3). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive low-dose oral imatinib mesylate once daily in the absence of disease progression or unacceptable toxicity.
Arm II: Patients receive high-dose oral imatinib mesylate twice daily in the absence of disease progression or unacceptable toxicity.

In the event of disease progression, patients on arm I may cross over to arm II and receive high-dose imatinib mesylate. Patients who continue to progress despite treatment with high-dose imatinib mesylate are removed from the study.

After completion of study therapy, patients are followed periodically.

Enrollment

946 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed gastrointestinal stromal tumor (GIST)
- Metastatic or unresectable disease
Immunohistochemical confirmation of KIT (CD117) expression by tumor as documented by DAKO antibody staining
Measurable or non-measurable disease by conventional imaging (CT scan or MRI) or physical examination
- If a target lesion has been previously embolized or irradiated, there must be objective evidence of progression to be considered for response assessment
No known brain metastasis

PATIENT CHARACTERISTICS:

WHO performance status 0-3
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN if hepatic metastases are present)
Creatinine ≤ 1.5 times ULN
ANC ≥ 1,000/mm³
Platelet count ≥ 100,000/mm³
Hemoglobin ≥ 9 g/dL (transfusions allowed)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for up to 3 months after completion of study therapy
No NYHA class III-IV cardiac disease
No congestive heart failure or myocardial infarction within the past 2 months
No severe and/or uncontrolled concurrent medical disease (e.g., uncontrolled diabetes, uncontrolled chronic renal or liver disease, or active uncontrolled infection [e.g., HIV])
No other prior malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
No medical, psychological, familial, sociological, or geographical condition that, in the opinion of the investigator, may preclude the patient's ability to tolerate or complete study treatment, comply with study protocol and follow-up schedule, or give reliable informed consent

PRIOR CONCURRENT THERAPY:

Recovered from all prior therapy
More than 28 days since prior chemotherapy, biologic therapy, or any other investigational drug
More than 14 days since prior major surgery
No concurrent therapeutic anticoagulation with coumarin derivatives
- Concurrent therapeutic anticoagulation with low-molecular weight heparin allowed
- Concurrent mini-dose coumarin derivatives (i.e., equivalent to 1 mg of oral warfarin daily) as prophylaxis allowed
No concurrent cytokines (i.e., filgrastim [G-CSF] or sargramostim [GM-CSF]) to support blood counts
No other concurrent investigational drugs
No other concurrent anticancer agents, including chemotherapy, radiotherapy, or anticancer biologic therapy