Breast Cancer
Conditions
Keywords
stage IV breast cancer, recurrent breast cancer
Brief summary
RATIONALE: Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining imatinib mesylate with capecitabine may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving imatinib mesylate together with capecitabine works in treating women with progressive stage IV breast cancer.
Detailed description
OBJECTIVES: * Determine the confirmed complete and partial response rate in women with progressive stage IV adenocarcinoma of the breast treated with imatinib mesylate and capecitabine. * Determine the 6-month progression-free survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients. * Correlate, preliminarily, c-kit and platelet-derived growth factor receptor expression with estrogen and progesterone receptor status, response, survival, and time to disease progression in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive oral imatinib mesylate\* once daily on days 1-21 and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. NOTE: \*If the patient tolerates the starting dose of imatinib mesylate in course 1, the dose will be increased in subsequent courses. Patients are followed every 6 months for 3 years. PROJECTED ACCRUAL: A total of 25-70 patients (25-45 patients with measurable disease and 25 with non-measurable disease) will be accrued for this study within 2 years.
Interventions
DRUGCapecitabine
1,000 mg/m\^2 by mouth twice daily Days 1-14 of each 21 day cycle
DRUGImatinib mesylate
400 mg by mouth daily
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed adenocarcinoma of the breast * Stage IV measurable disease * Disease progression after at least 1, but no more than 2, prior chemotherapy regimens for metastatic disease * Patients with hormone-sensitive tumors must have received prior hormonal therapy * Patients with human epidermal growth factor receptor 2 (HER2)/neu-overexpressing tumors (3+ by immunohistochemistry or amplified by fluorescent in situ hybridization) should have received trastuzumab (Herceptin®) in the adjuvant or metastatic setting (unless contraindicated) * No clinical evidence of or known brain or central nervous system (CNS) disease * Hormone Receptor status known * Female age 18 and over * Performance status Zubrod 0-2 * Absolute neutrophil count \> 1,500/mm\^3 * Leukocyte count \> 3,000/mm\^3 * Platelet count \> 100,000/mm\^3 * Bilirubin normal * aspartate aminotransferase (AST) / alanine aminotransferase (ALT) \< 2.5 times upper limit of normal * Creatinine normal OR Creatinine clearance \> 60 mL/min * Not pregnant or nursing * Fertile patients must use effective contraception during and for 3 months after study participation * No history of severe hypersensitivity reaction to compounds of similar chemical or biological composition to imatinib mesylate, capecitabine, or fluorouracil * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No prior biologic therapy (e.g., vaccines) * No concurrent filgrastim (G-CSF) for chemotherapy-induced neutropenia * No prior capecitabine or fluorouracil for metastatic breast cancer * Prior hormonal therapy allowed * More than 4 weeks since prior radiotherapy - Previously irradiated area(s) must not be the only site of disease * More than 4 weeks since prior major surgery * More than 4 weeks since prior therapy for breast cancer * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational or commercial agents or therapies for metastatic breast cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed Response Rate (Complete and Partial) | 12 weeks | Number of participants with confirmed complete or partial response. Confirmed response (complete and partial) per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (V1.0). Complete Response (CR) is complete disappearance of all measurable and non-measurable disease; no new lesions; no disease related symptoms; and normalization of markers and other abnormal lab values. Partial response (PR) applies only to patients with at least one measurable lesion. PR is greater than or equal to 30% decrease under baseline of the sum of longest diameter of all target measurable lesions; no unequivocal progression of non-measurable disease and no new lesions. Confirmed response is two or more objective statuses a minimum of four weeks apart documented before progression or symptomatic deterioration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival at 6 Months | Six months | Percentage of participants progression-free at 6 months. Progression-free survival (PFS) measured from date of registration to first observation of progressive disease (per RECIST criteria (V1.0)), death due to any cause, or symptomatic deterioration. Kaplan-Meier was used to estimate progression-free survival (PFS) at six months. |
| Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Every 3 weeks while on treatment for up to 3 years. | Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5= Fatal. Only adverse events that are possibly, probably or definitely related to study drug are reported. |
Participant flow
Recruitment details
The study was activated June 15, 2004. It was open to SWOG institutions who obtained Institutional Review Board (IRB) approval for this study. 27 patients were enrolled at 16 institutions. The study was temporarily closed to accrual April 19, 2005 to allow assessment of response in the first stage. It was closed permanently on December 15, 2005.
Participants by arm
| Arm | Count |
|---|---|
| Imatinib Mesylate & Capecitabine Imatinib Mesylate 400 mg by mouth daily for 21 day cycle. Capecitabine 1,000 mg/m\^2 by mouth twice daily Days 1-14 of each 21 day cycle. | 27 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Ineligible | 6 |
Baseline characteristics
| Characteristic | Imatinib Mesylate & Capecitabine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 55.3 years STANDARD_DEVIATION 10.6 |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 4 / 20 |
Outcome results
Primary
Confirmed Response Rate (Complete and Partial)
Number of participants with confirmed complete or partial response. Confirmed response (complete and partial) per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (V1.0). Complete Response (CR) is complete disappearance of all measurable and non-measurable disease; no new lesions; no disease related symptoms; and normalization of markers and other abnormal lab values. Partial response (PR) applies only to patients with at least one measurable lesion. PR is greater than or equal to 30% decrease under baseline of the sum of longest diameter of all target measurable lesions; no unequivocal progression of non-measurable disease and no new lesions. Confirmed response is two or more objective statuses a minimum of four weeks apart documented before progression or symptomatic deterioration.
Time frame: 12 weeks
Population: Eligible participants who received treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imatinib Mesylate & Capecitabine | Confirmed Response Rate (Complete and Partial) | 2 participants |
Secondary
Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Adverse Events (AEs) are reported by the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5= Fatal. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: Every 3 weeks while on treatment for up to 3 years.
Population: Eligible participants who received any treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Imatinib Mesylate & Capecitabine | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Diarrhea | 2 Participants |
| Imatinib Mesylate & Capecitabine | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Fatigue (asthenia, lethargy, malaise) | 2 Participants |
| Imatinib Mesylate & Capecitabine | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Leukocytes (total WBC) | 1 Participants |
| Imatinib Mesylate & Capecitabine | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Mucositis/stomatitis (clinical exam) - Oral cavity | 1 Participants |
| Imatinib Mesylate & Capecitabine | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neuropathy: motor | 1 Participants |
| Imatinib Mesylate & Capecitabine | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neuropathy: sensory | 1 Participants |
| Imatinib Mesylate & Capecitabine | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Neutrophils/granulocytes (ANC/AGC) | 1 Participants |
| Imatinib Mesylate & Capecitabine | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Pain - Abdomen NOS | 1 Participants |
| Imatinib Mesylate & Capecitabine | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Pain - Muscle | 1 Participants |
| Imatinib Mesylate & Capecitabine | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Rash/desquamation | 1 Participants |
| Imatinib Mesylate & Capecitabine | Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug | Rash: hand-foot skin reaction | 2 Participants |
Secondary
Progression-free Survival at 6 Months
Percentage of participants progression-free at 6 months. Progression-free survival (PFS) measured from date of registration to first observation of progressive disease (per RECIST criteria (V1.0)), death due to any cause, or symptomatic deterioration. Kaplan-Meier was used to estimate progression-free survival (PFS) at six months.
Time frame: Six months
Population: Eligible participants who received treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Imatinib Mesylate & Capecitabine | Progression-free Survival at 6 Months | 16 percentage of participants |