Ductal Carcinoma In Situ
Conditions
Keywords
Ductal Carcinoma In Situ, Breast Cancer, Herceptin, Trastuzumab, DCIS
Brief summary
Primary Objectives: * To determine the effect of a single dose of Herceptin (trastuzumab) on the proliferation rate of Her-2/neu over-expressing ductal carcinoma in situ (DCIS) * To evaluate the effect of a single dose of Herceptin on the apoptotic index of Her-2/neu over-expressing DCIS
Detailed description
Herceptin (Trastuzumab) stops or slows the growth of certain breast cancer cells by blocking the chemical signals they need to grow. As part of your standard care for DCIS, you will have a complete routine physical exam, a mammogram of both breasts, and blood (about 2 tablespoons) will be drawn for routine tests. Some of your leftover breast biopsy tissue will be tested for Her-2/neu expression. Blood will be drawn (about 2-6 teaspoons) to check if your bone marrow (red blood cells), kidney, and liver are functioning well enough to have this treatment. Women who are able to have children must have a negative blood pregnancy test before starting treatment. If you are eligible to take part in this study, you will receive one dose of trastuzumab at least 2 weeks before your surgery. The dose of trastuzumab will be given intravenously (through a needle in a vein in your arm) as a steady infusion over 90 minutes, on an outpatient basis. You will be checked during the infusion and for 1 hour after it is completed. You will have routine surgery for DCIS (either segmental mastectomy, mastectomy with or without reconstruction, and possible sentinel lymph node biopsy) approximately 14 to 28 days after being given Herceptin. If a segmental mastectomy was performed as part of our standard practice you will be evaluated by a radiation oncologist following surgery. After your surgery, patients will also be evaluated by a breast medical oncologist to determine if any additional standard therapy is needed. Tissue that is left over from the original breast biopsy and surgery will be tested for various biomarkers (substances which indicate the severity or spread of cancer), cancer growth rate, and apoptotic index (cell death rate). This is an investigational study. The FDA has approved trastuzumab for the treatment of breast cancer. Up to 71 patients will take part in this study. All will be enrolled at M. D. Anderson.
Interventions
8 mg/kg IV Over 90 Minutes
Sponsors
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. All patients with histologic confirmation of DCIS (TisN0M0) that is Her-2/neu 3+ positive by immunohistochemistry (IHC) and/or positive for Her-2 gene amplification by fluorescence in situ hybridization (FISH) will be eligible for the study. 2. Patients must sign informed consent indicating that they are aware of the investigational nature of the study, in keeping with institutional policy. 3. Those patients with history of other contralateral non-invasive and invasive breast and non-breast malignancies are eligible to participate unless they have previously received a doxorubicin dose of more than 400 mg/m2. 4. All patients should have adequate bone marrow function, as defined by peripheral granulocyte count of \> 1,500/mm3, and platelet count \> 100,000 mm3. Patients must have adequate liver function, with bilirubin within normal laboratory values. In addition, patients should have adequate renal function, defined as serum creatinine \< 2.0 mg/dl. 5. Patients with intact primary tumors will be eligible for this study. Patients who have had their diagnostic biopsy at an outside facility but still have measurable disease on presentation will be eligible. 6. Patients with history of cardiac arrhythmia will be eligible for study after being seen by cardiology and deemed good candidates for participation. 7. Women of child bearing potential must have a negative urine or serum pregnancy test.
Exclusion criteria
1. Patients with a current known invasive breast cancer are not eligible for this study. 2. All patients who are Her-2/neu negative will be ineligible for the study. 3. Patients with history of congestive heart failure will be excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Proliferation as Measured by Ki-67 | Before and after single dose of Herceptin approximately 21 days before surgery for ductal carcinoma in situ (DCIS), up to 4 weeks | Percent Change in Proliferation as measured by Ki-67 (% nuclei stained). Comparison of proliferation rates of Her-2/neu overexpressing cells before and after treatment with Herceptin per Participant where absolute change defined as difference of increase/decrease. Proliferation rate evaluated by immunohistochemistry using paraffin-embedded sections and monoclonal antibody for ki-67. |
| Number of Participants Achieving Documented Change in Proliferation | Before and after single dose of Herceptin approximately 21 days before DCIS surgery, up to 4 weeks | Proliferation rate and apoptotic index measured on core biopsy specimen and resection specimen from each participants. To compare Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and CD4+ T-cell response in each participant observed at pre- and post-treatment times, paired analysis was performed using Student's t-test. Nonparametric Wilcoxon rank sum test was used to compare data between groups. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent of Ki-67 | Before and after single dose of Herceptin approximately 21 days before DCIS surgery, up to 4 weeks | Mean percent of Ki-67 (% nuclei stained) at immunohistochemical staining performed for biomarkers. Tissue sections from diagnostic core biopsy tissue that contains DCIS before treatment and from corresponding tissues that contain DCIS from the surgical resection obtained after a single dose of Herceptin. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: March 2005 - November 2010. All recruitment was at UT MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Herceptin 8 mg/kg intravenously (IV) Over 90 Minutes | 69 |
| Total | 69 |
Baseline characteristics
| Characteristic | Herceptin |
|---|---|
| Age, Continuous | 53 years |
| Region of Enrollment United States | 69 participants |
| Sex: Female, Male Female | 69 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 | 0 / 69 |
| serious Total, serious adverse events | 3 / 69 |
Outcome results
Primary
Number of Participants Achieving Documented Change in Proliferation
Proliferation rate and apoptotic index measured on core biopsy specimen and resection specimen from each participants. To compare Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and CD4+ T-cell response in each participant observed at pre- and post-treatment times, paired analysis was performed using Student's t-test. Nonparametric Wilcoxon rank sum test was used to compare data between groups.
Time frame: Before and after single dose of Herceptin approximately 21 days before DCIS surgery, up to 4 weeks
Population: Twelve evaluable patients were required to characterize the change in proliferation rate after treatment with a single dose of Herceptin (trastuzumab). Those participants who completed Herceptin administration, surgery, and post surgery bio-markers testing were evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Herceptin | Number of Participants Achieving Documented Change in Proliferation | 12 Participants |
Primary
Percent Change in Proliferation as Measured by Ki-67
Percent Change in Proliferation as measured by Ki-67 (% nuclei stained). Comparison of proliferation rates of Her-2/neu overexpressing cells before and after treatment with Herceptin per Participant where absolute change defined as difference of increase/decrease. Proliferation rate evaluated by immunohistochemistry using paraffin-embedded sections and monoclonal antibody for ki-67.
Time frame: Before and after single dose of Herceptin approximately 21 days before surgery for ductal carcinoma in situ (DCIS), up to 4 weeks
Secondary
Mean Percent of Ki-67
Mean percent of Ki-67 (% nuclei stained) at immunohistochemical staining performed for biomarkers. Tissue sections from diagnostic core biopsy tissue that contains DCIS before treatment and from corresponding tissues that contain DCIS from the surgical resection obtained after a single dose of Herceptin.
Time frame: Before and after single dose of Herceptin approximately 21 days before DCIS surgery, up to 4 weeks
Population: Analysis was per protocol. Twelve evaluable patients were required to characterize the change in proliferation rate after treatment with a single dose of Herceptin (trastuzumab). Those participants who completed Herceptin administration, surgery, and post surgery bio-markers testing were evaluable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Herceptin | Mean Percent of Ki-67 | 44.29 Percentage of Ki-67 | Standard Deviation 3.42 |