Phase III Randomized, Intergroup Trial Assessing the Clinical Activity Of STI-571 at Two Dose Levels in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors (GIST) Expressing the Kit Receptor Tyrosine Kinase (CD117)
Phase III Randomized, Intergroup Trial Assessing the Clinical Activity Of STI-571 at Two Dose Levels in Patients With Unresectable or Metastatic Gastrointestinal Stromal Tumors (GIST) Expressing the Kit Receptor Tyrosine Kinase (CD117)
Randomized phase III trial to compare the effectiveness of two different doses of STI571 in treating patients who have metastatic or unresectable gastrointestinal stromal tumor. STI571 may interfere with the growth of tumor cells and may be an effective treatment for cancer. It is not yet known which dose of STI571 is more effective in treating gastrointestinal stromal tumors.
PRIMARY OBJECTIVES:
I. Compare the overall and progression-free survival of patients with CD117-expressing metastatic or unresectable gastrointestinal stromal tumor treated with two different doses of imatinib mesylate.
II. Compare the confirmed, unconfirmed, complete, and partial response rates in patients treated with these regimens.
III. Compare the toxic effects of these regimens in these patients.
OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms.
Arm I: Patients receive oral imatinib mesylate once daily.
Arm II: Patients receive oral imatinib mesylate twice daily.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients in arm I with progressive disease may cross over to arm II and receive treatment in the absence of further disease progression.
Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 600 patients will be accrued for this study within 24 months.
Inclusion Criteria:
Patient must have a biopsy proven diagnosis of gastrointestinal stromal tumor (GIST) which is distantly metastatic or unresectable; tumors must meet BOTH of the following criteria:
Patient must have measurable or non-measurable disease by conventional scan imaging (CT or MRI) or physical examination; tests used to assess disease must have been performed within 28 days prior to registration; if a target lesion has been previously embolized or irradiated, there must be objective evidence of progression to be considered for response assessment
Patient must have an identified team (including a medical oncologist and a surgeon) to provide care
Patient must not have known brain metastasis
Patient must have a Zubrod performance status of 0 - 3
Patient must have resolution of transient toxicities from any prior therapy to =< grade 1 (NCI-CTC version 2.0)
The patient must not have received chemotherapy, biologic therapy or any other investigational drug for any reason within 28 days prior to registration; patients must not have had a major surgery within 14 days prior to registration
If day 14 or 28 falls on a weekend or holiday, the limit may be extended to the next working day
No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, 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
All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
At the time of patient registration, the treating institution's name and ID number must be provided to the Data Operations Center in Seattle in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered into the data base
Patients on lower dose arm (Arm 1) will be allowed to increase the daily dose of STI-571 in the case of disease progression; if there is questionable disease progression, the treating investigator should contact the primary Study Coordinator, Dr. George Demetri at 617/632-3985 to review progression information and discuss treatment options
Sacramento, California 95817, United States
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Baltimore, Maryland 21287, United States
Ann Arbor, Michigan 48106, United States
Springfield, Missouri 65804, United States
Berlin Corners, Vermont 05602, United States