Recurrent Gastric Cancer, Stage IV Gastric Cancer
Conditions
Brief summary
Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. This phase II trial is studying how well imatinib mesylate works in treating patients with refractory metastatic and/or unresectable stomach or gastroesophageal junction cancer.
Detailed description
PRIMARY OBJECTIVES: I. To determine the response rate, time to tumor progression, and overall survival in patients with metastatic gastric cancer treated with STI571 who have failed one chemotherapy regimen for metastatic disease. II. To assess the toxicities of STI571 in these patients. III. To obtain preliminary data on molecular correlates to determine clinical efficacy and toxicity. OUTLINE: This is a multicenter study. Patients are stratified according to risk (good risk \[chemonaïve\] vs poor risk \[1 prior chemotherapy regimen\]). Patients receive oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed for 30 days. PROJECTED ACCRUAL: A total of 21-41 patients will be accrued for this study within 1-1.5 years.
Interventions
DRUGimatinib mesylate
Given orally
OTHERlaboratory biomarker analysis
Correlative studies
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with metastatic and/or unresectable carcinoma of the stomach, who have measurable disease * Life expectancy \> 3 months * Karnofsky Performance Status \> 60% * Absence of an active infection * Granulocyte count of \> 1,500/mm\^3 * Hemoglobin (Hgb) \>= 9 mg/dl * Serum bilirubin =\< 1.5 mg/dl, regardless of liver involvement secondary to tumor * Platelets \> 100,000/mm\^3 * Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) \< 2.5 x the institutional upper limit of normal * Calculated creatinine clearance of \> 60 ml/min * Patients must have signed written informed consent * Female patients of child-bearing potential must have a negative blood or urine pregnancy test within two weeks prior to initial study treatment * Patients who have had prior chemotherapy or radiation therapy must have recovered from any toxicities prior to study entry * Patients must have radiographic imaging to document measurable disease within 28 days prior to initial study therapy
Exclusion criteria
* Diagnosis of resectable carcinoma of the stomach * Major surgery within four weeks of study entry * Brain metastasis or known seizure disorder * Fertile men and women not using an acceptable method of contraception * Pregnant or lactating patients are excluded since STI571 may be harmful to the developing fetus and child * Patients known to be HIV positive and receiving HAART are excluded because of possibly pharmacological interactions * Active peptic ulceration or active gastrointestinal bleeding or any active bleeding disorders * Use of therapeutic doses of coumadin (warfarin) as anticoagulation * Medical, social, or psychological factors which would prevent the patient from completing the treatment protocol * Patients with serious intercurrent illness which would preclude tolerance and completion of the protocol treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Up to 6 years | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by X-Ray, MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR |
| Toxicity Summary | Up to 30 days post treatment | Toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. Grade 3 and above adverse events possibly, probably or definitely related to treatment. |
| Progression-free Survival | From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 30 days post treatment | Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Overall Survival | From first day of treatment to time of death due to any cause, assessed up to 5 years post-treatment | Will be summarized using the Kaplan-Meier product-limit estimators. |
| Time to Treatment Failure | From first day of treatment until discontinuation of treatment, assessed up to 30 days post treatment | Defined as the time from start of treatment to the discontinuation of treatment for any reason, including disease progression, treatment toxicity, patient preference, or death Will be summarized using the Kaplan-Meier product-limit estimators. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions |
| Baseline Gene Expression Levels of the Target Genes (PDGF-R and PDGF), Genes Associated With Induction of Apoptosis (Bcl-2, Bax), and Cell Cycle Regulatory Genes (p53, p21, p27 | Baseline | Will summarized overall and according to response and toxicity (if numbers permit), using medians, quartiles and ranges - or if a transformation is found to render the data compatible with the normal assumptions, with means, standard deviations, and confidence intervals. The association with progression-free survival or overall survival will be assessed by dichotomizing the measures of gene expression at the median (or by previously established cut-points) and constructing Kaplan-Meier plots. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Imatinib Mesylate) Patients receive 400 mg oral imatinib mesylate twice daily on days 1-28. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
imatinib mesylate: Given orally
laboratory biomarker analysis: Correlative studies | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Treatment (Imatinib Mesylate) |
|---|---|
| Age, Continuous | 60 years |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 17 / 17 |
| serious Total, serious adverse events | 8 / 17 |
Outcome results
Primary
Baseline Gene Expression Levels of the Target Genes (PDGF-R and PDGF), Genes Associated With Induction of Apoptosis (Bcl-2, Bax), and Cell Cycle Regulatory Genes (p53, p21, p27
Will summarized overall and according to response and toxicity (if numbers permit), using medians, quartiles and ranges - or if a transformation is found to render the data compatible with the normal assumptions, with means, standard deviations, and confidence intervals. The association with progression-free survival or overall survival will be assessed by dichotomizing the measures of gene expression at the median (or by previously established cut-points) and constructing Kaplan-Meier plots.
Time frame: Baseline
Population: Gene data were not collected. Due to budget constraints and recent reprioritizations, CTEP closed the study to accrual prior to collection of correlative data.
Primary
Overall Survival
Will be summarized using the Kaplan-Meier product-limit estimators.
Time frame: From first day of treatment to time of death due to any cause, assessed up to 5 years post-treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Imatinib Mesylate) | Overall Survival | 3.25 Months |
Primary
Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 30 days post treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Imatinib Mesylate) | Progression-free Survival | 1.35 Months |
Primary
Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by X-Ray, MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 6 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment (Imatinib Mesylate) | Response Rate | 0 percentage of patients responding |
Primary
Time to Treatment Failure
Defined as the time from start of treatment to the discontinuation of treatment for any reason, including disease progression, treatment toxicity, patient preference, or death Will be summarized using the Kaplan-Meier product-limit estimators. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Time frame: From first day of treatment until discontinuation of treatment, assessed up to 30 days post treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment (Imatinib Mesylate) | Time to Treatment Failure | 0.98 Months |
Primary
Toxicity Summary
Toxicity assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 2.0. Grade 3 and above adverse events possibly, probably or definitely related to treatment.
Time frame: Up to 30 days post treatment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Hypokalemia | 1 Participants |
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Alkaline phosphatase increased | 1 Participants |
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Anorexia | 1 Participants |
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Constipation | 1 Participants |
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Fatigue | 1 Participants |
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Hyperglycemia | 1 Participants |
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Hemoglobin decreased | 1 Participants |
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Hypoxia | 1 Participants |
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Abdominal pain | 1 Participants |
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Hypophosphatemia | 2 Participants |
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Hyponatremia | 1 Participants |
| Treatment (Imatinib Mesylate) | Toxicity Summary | Grade 3 : Packed red blood cell transfusion | 3 Participants |