Breast Cancer
Conditions
Keywords
recurrent breast cancer, stage IV breast cancer, male breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Imatinib mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving gemcitabine together with imatinib mesylate may kill more tumor cells. PURPOSE: This randomized phase II trial is studying gemcitabine and imatinib mesylate to see how well they work compared to gemcitabine alone in treating patients with previously treated locally advanced or metastatic breast cancer.
Detailed description
OBJECTIVES: Primary * Compare time to progression in patients with previously treated locally advanced or metastatic breast cancer treated with gemcitabine hydrochloride with vs without imatinib mesylate. Secondary * Compare the efficacy of these regimens in these patients. * Compare the overall survival of patients treated with these regimens. * Compare the safety and tolerability of these regimens in these patients. OUTLINE: This is a multicenter, open-label, randomized study. Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive gemcitabine hydrochloride IV on days 3 and 10. * Arm II: Patients receive gemcitabine hydrochloride IV on days 3 and 10 and oral imatinib mesylate once daily on days 1-5 and 8-12. In both arms, treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.
Interventions
DRUGgemcitabine hydrochloride
Given IV
DRUGimatinib mesylate
Given orally
Sponsors
National Cancer Institute (NCI)
Novartis Pharmaceuticals
Rutgers Cancer Institute of New Jersey
Rutgers, The State University of New Jersey
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed breast cancer * Locally advanced or metastatic disease * Disease progression after at least 1 prior chemotherapy regimen for metastatic disease * No more than 2 prior chemotherapy regimens for metastatic disease (prior neoadjuvant or adjuvant treatment will not be included in determining the number of prior chemotherapy regimens) * Measurable disease * No known symptomatic or untreated brain metastases or carcinomatous meningitis * Previously treated and clinically stable brain metastases allowed provided patient has been off steroids for \> 7 days * Hormone receptor status not specified PATIENT CHARACTERISTICS: * Male or female * Menopausal status not specified * ECOG performance status 0-2 * Life expectancy ≥ 3 months * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * AST or ALT ≤ 2.5 times ULN * Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study therapy * Able to swallow oral medication * No coexisting medical condition that would preclude study compliance * No uncontrolled illness, including any of the following: * Symptomatic congestive heart failure * Unstable angina pectoris * Cardiac arrhythmia requiring therapy * Myocardial infarction within the past 6 months * Active infection * No New York Heart Association class III-IV cardiac disease * No history of allergic reaction attributed to compounds of similar chemical or biologic composition to gemcitabine hydrochloride and/or imatinib mesylate * No other primary malignancies within the past 5 years except for carcinoma in situ of the cervix or nonmelanoma skin cancer * No known chronic liver disease (i.e., chronic active hepatitis or cirrhosis) * No known HIV infection PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from all prior therapy * More than 2 weeks since prior surgery * At least 2 weeks since prior hormonal therapy * At least 2 weeks since prior trastuzumab (Herceptin®) * At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas) * At least 3 weeks since prior anti-vascular endothelial growth factor therapy * More than 28 days since prior investigational agents * At least 3 weeks since prior radiotherapy * Must have evidence of ≥ 1 measurable target lesion outside the irradiated fields OR radiologically confirmed disease progression within the irradiated fields after completion of radiotherapy * No prior imatinib mesylate for metastatic disease * No prior gemcitabine hydrochloride for metastatic disease * More than 6 months since prior adjuvant gemcitabine hydrochloride * No other concurrent investigational or commercial agents * No concurrent therapeutic anticoagulation with warfarin (e.g., Coumadin® or Coumadine®) * Concurrent heparin or low-molecular weight heparin (e.g., Lovenox®) for therapeutic anticoagulation allowed * Concurrent prophylactic warfarin therapy (e.g., mini-dose Coumadin® ≤ 1 mg daily) to maintain catheter patency allowed * No concurrent routine chronic systemic corticosteroids * No concurrent medications that would preclude study compliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | 5 years | Sample size of 40 patients per group was needed to detect an 8 month increase in time to progression with the combination (80% power, alpha =.05, 2-sided). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Complete and Partial Response) | 5 years | Overall response rate was evaluated every 2 cycles (six weeks) for both groups using international criteria by the Response Evaluation Criteria in Solid Tumors (RECISTv1.0) for target lesions and were assessed by CT or MRI. Response rates were defined as 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) defined as OR=CR + PR |
| Overall Survival | 5 years | — |
Countries
United States
Participant flow
Recruitment details
This study was opened to accural on 5/1/2006 and was closed to accrual on 4/15/2011 due to slow accrual. Subjects were recruited through the Cancer Institute of New Jersey Oncology Group. We are reporting results on 49 eligible patients. One was not eligible for participation.
Participants by arm
| Arm | Count |
|---|---|
| Arm I Patients receive gemcitabine hydrochloride 1250 mg/m2 intravenously on days 3 and 10.
gemcitabine hydrochloride: Given IV | 26 |
| Arm II Patients receive gemcitabine hydrochloride 1250 mg/m2 intravenously on days 3 and 10 and oral imatinib mesylate 400 mg orally once daily on days 1-5 and 8-12.
gemcitabine hydrochloride: Given IV
imatinib mesylate: Given orally | 23 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | brain mets discovered prior to treatment | 1 | 0 |
Baseline characteristics
| Characteristic | Arm I | Arm II | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 10 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 13 Participants | 28 Participants |
| Age, Continuous | 60.7 years | 62.4 years | 61.5 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 22 Participants | 46 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 6 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 16 Participants | 33 Participants |
| Region of Enrollment United States | 26 participants | 23 participants | 49 participants |
| Sex: Female, Male Female | 26 Participants | 23 Participants | 49 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 2 / 23 |
| other Total, other adverse events | 26 / 26 | 23 / 23 |
| serious Total, serious adverse events | 5 / 26 | 6 / 23 |
Outcome results
Primary
Time to Progression
Sample size of 40 patients per group was needed to detect an 8 month increase in time to progression with the combination (80% power, alpha =.05, 2-sided).
Time frame: 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Gemcitabine Hydrochloride) | Time to Progression | 2 months |
| Arm II (Gemcitabine Hydrochloride + Imatinib) | Time to Progression | 2.5 months |
p-value: 0.3Log Rank
Secondary
Overall Survival
Time frame: 5 years
Population: This study was prematurely closed so overall survival was not analyzed.
Secondary
Response Rate (Complete and Partial Response)
Overall response rate was evaluated every 2 cycles (six weeks) for both groups using international criteria by the Response Evaluation Criteria in Solid Tumors (RECISTv1.0) for target lesions and were assessed by CT or MRI. Response rates were defined as 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) defined as OR=CR + PR
Time frame: 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Gemcitabine Hydrochloride) | Response Rate (Complete and Partial Response) | 9.1 percentage of participants |
| Arm II (Gemcitabine Hydrochloride + Imatinib) | Response Rate (Complete and Partial Response) | 9.1 percentage of participants |