Gastrointestinal Stromal Tumor
Conditions
Brief summary
Phase II trial to study the effectiveness of neoadjuvant and adjuvant imatinib mesylate in treating patients who are undergoing surgery for primary or recurrent malignant gastrointestinal stromal tumor. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving imatinib mesylate before and after surgery may shrink the tumor so it can be removed and may kill any tumor cells remaining after surgery.
Detailed description
OBJECTIVES: I. Determine the progression-free survival of patients with primary or recurrent potentially resectable malignant gastrointestinal stromal tumor treated with neoadjuvant and adjuvant imatinib mesylate. II. Determine the objective response rate of patients treated with this drug. III. Determine the safety of this drug in these patients. OUTLINE: Patients receive oral imatinib mesylate once daily. Treatment continues for 8 weeks in the absence of disease progression. Patients with disease progression are considered for immediate surgical resection. Otherwise, after 8 weeks, patients undergo surgical resection to debulk all gross tumor. Two to four weeks after surgery, patients receive oral imatinib mesylate once daily for 2 years. Patients are followed every 3 months for 2 years and then every 6 months for 3 years.
Interventions
PROCEDUREConventional Surgery
Undergo surgical resection
DRUGImatinib Mesylate
Given orally
Sponsors
American College of Radiology Imaging Network
Eastern Cooperative Oncology Group
Radiation Therapy Oncology Group
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed malignant gastrointestinal stromal tumor * Potentially resectable primary disease * Potentially resectable recurrent disease * Local or intra-abdominal/pelvic metastatic disease * Documented c-kit (CD117) expression by immunohistochemical analysis of either initial core specimen or, if recurrent disease, from original tumor block * Primary disease must be visceral, intra-abdominal, or pelvic in origin * At least 1 unidimensionally measurable lesion * At least 5 cm for primary disease * At least 2 cm for recurrent disease * At least 1 viable core biopsy tumor specimen obtained within 8 weeks before registration * Performance status - Zubrod 0-2 * WBC at least 3,000/mm\^3 * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Bilirubin no greater than 1.5 times upper limit of normal (ULN) * ALT/AST no greater than 2.5 times ULN * No uncontrolled chronic liver disease * Creatinine no greater than 1.5 times ULN * No uncontrolled chronic renal disease * No New York Heart Association class III or IV cardiac disease * Must be able to lie still in the PET scanner for approximately 1-2 hours * No uncontrollable hyperglycemia * No medical or psychological condition that would preclude study participation * No severe or uncontrolled medical disease * No active uncontrolled infection * No known or suspected hypersensitivity to any component of the study drug * Any prior malignancy is allowed provided patient remains disease free from that malignancy * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective barrier contraception during and for 3 months after study participation * At least 28 days since prior biologic therapy * No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) * At least 28 days since prior chemotherapy * At least 28 days since prior radiotherapy * See Disease Characteristics * At least 28 days since prior investigational drugs * At least 28 days since prior imatinib mesylate * No concurrent therapeutic doses of warfarin * Concurrent low-molecular weight heparin or mini-dose warfarin (1 mg per day) prophylaxis is allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Disease Progression at 2 Years | From registration to two years | Kaplan-Meier estimate of disease progression rate. Disease progression is determined by Response Evaluation Criteria in Solid Tumours criteria (RECIST). RECIST criteria is described here: http://ctep.cancer.gov/protocolDevelopment/docs/recist\_guideline.pdf |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rates of Objective Response (Complete, Partial, and Stable) | Pretreatment and prior to surgery (at 4-10 weeks, based on surgery timing) | The percentage of patients who achieved a complete, partial or stable response prior to surgery as assessed by Response Evaluation Criteria in Solid Tumours criteria (RECIST). RECIST criteria is described here: http://ctep.cancer.gov/protocolDevelopment/docs/recist\_guideline.pdf. |
| Percentage of Patients With Major Toxicity (Toxicity Grade ≥ 3) | Analysis occurs after all patients have been on study for at least 2 years. Measured from start of treatment to end of follow-up, to a maximum of 4.95 years. | Highest grade toxicity per subject was counted. Toxicities were graded using Common Toxicity Criteria (CTC) v 2.0. Grade refers to the severity of the toxicity, using Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity. |
| FDG-PET as Biological Marker of Metabolic Response(MR) During Imatinib Mesylate (IM) Treatment, in Patients With GIST Who Are naı¨ve to Tyrosine Kinase Inhibitor Therapy | change from baseline to 1 week post therapy | evaluate FDG-PET as a non-invasive functional imaging tool to assess in situ tumor metabolism (as measured by the Standardized Uptake Values of FDG in the tumor) prior to and during the administration of IM. %change in SUVmax \<1 indicate decreased tumor metabolism while values \>1 indicated an increase in tumor metabolism. Metabolic response by 18F-FDG PET was determined in accordance with the criteria of the European Organization for Research and Treatment of Cancer EORTC), with increases or decreases of more than 25% in SUVmax defining progressive metabolic disease (PMD) and partial metabolic response (PMR), respectively, and new lesions defining PMD. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Imatinib Mesylate Patients receive oral imatinib mesylate once daily. Treatment continues for 8 weeks in the absence of disease progression. Patients with disease progression are considered for immediate surgical resection. Otherwise, after 8 weeks, patients undergo surgical resection to debulk all gross tumor. Two to four weeks after surgery, patients receive oral imatinib mesylate once daily for 2 years. | 52 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible | 8 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Imatinib Mesylate |
|---|---|
| Age, Continuous | 58.5 years |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 52 / 52 |
| serious Total, serious adverse events | 22 / 52 |
Outcome results
Primary
Rate of Disease Progression at 2 Years
Kaplan-Meier estimate of disease progression rate. Disease progression is determined by Response Evaluation Criteria in Solid Tumours criteria (RECIST). RECIST criteria is described here: http://ctep.cancer.gov/protocolDevelopment/docs/recist\_guideline.pdf
Time frame: From registration to two years
Population: All eligible patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imatinib Mesylate | Rate of Disease Progression at 2 Years | 13.8 percentage of participants |
Secondary
FDG-PET as Biological Marker of Metabolic Response(MR) During Imatinib Mesylate (IM) Treatment, in Patients With GIST Who Are naı¨ve to Tyrosine Kinase Inhibitor Therapy
evaluate FDG-PET as a non-invasive functional imaging tool to assess in situ tumor metabolism (as measured by the Standardized Uptake Values of FDG in the tumor) prior to and during the administration of IM. %change in SUVmax \<1 indicate decreased tumor metabolism while values \>1 indicated an increase in tumor metabolism. Metabolic response by 18F-FDG PET was determined in accordance with the criteria of the European Organization for Research and Treatment of Cancer EORTC), with increases or decreases of more than 25% in SUVmax defining progressive metabolic disease (PMD) and partial metabolic response (PMR), respectively, and new lesions defining PMD.
Time frame: change from baseline to 1 week post therapy
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Imatinib Mesylate | FDG-PET as Biological Marker of Metabolic Response(MR) During Imatinib Mesylate (IM) Treatment, in Patients With GIST Who Are naı¨ve to Tyrosine Kinase Inhibitor Therapy | -59.4 percentage change in SUVmax |
Secondary
Percentage of Patients With Major Toxicity (Toxicity Grade ≥ 3)
Highest grade toxicity per subject was counted. Toxicities were graded using Common Toxicity Criteria (CTC) v 2.0. Grade refers to the severity of the toxicity, using Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity.
Time frame: Analysis occurs after all patients have been on study for at least 2 years. Measured from start of treatment to end of follow-up, to a maximum of 4.95 years.
Population: All eligible patients who started study treatment (for pre-surgery), and who additionally had surgery (post-surgery)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imatinib Mesylate | Percentage of Patients With Major Toxicity (Toxicity Grade ≥ 3) | Pre-surgery | 34.6 percentage of participants |
| Imatinib Mesylate | Percentage of Patients With Major Toxicity (Toxicity Grade ≥ 3) | Post-surgery | 48.9 percentage of participants |
Secondary
Rates of Objective Response (Complete, Partial, and Stable)
The percentage of patients who achieved a complete, partial or stable response prior to surgery as assessed by Response Evaluation Criteria in Solid Tumours criteria (RECIST). RECIST criteria is described here: http://ctep.cancer.gov/protocolDevelopment/docs/recist\_guideline.pdf.
Time frame: Pretreatment and prior to surgery (at 4-10 weeks, based on surgery timing)
Population: Eligible patients who started study treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imatinib Mesylate | Rates of Objective Response (Complete, Partial, and Stable) | Complete Response | 0 percentage of participants |
| Imatinib Mesylate | Rates of Objective Response (Complete, Partial, and Stable) | Partial Response | 5.8 percentage of participants |
| Imatinib Mesylate | Rates of Objective Response (Complete, Partial, and Stable) | Stable Disease | 86.5 percentage of participants |