Breast Cancer
Conditions
Keywords
Breast Cancer, Carcinoma of the Breast, HER-2/neu Overexpression, Herceptin, Trastuzumab, GM-CSF, Sargramostim, Leukine
Brief summary
Primary Objectives: 1. To determine the patient's tumor response rate that this protocol will produce. 2. To determine the 1 year progression-free survival that this protocol will produce. Secondary Objective: 1\. To determine whether antibody-dependent cell-mediated cytotoxicity (ADCC) is the mechanism of overcoming Herceptin-resistance by use of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF).
Detailed description
GM-CSF stimulates the immune system and may increase the effectiveness of Herceptin. Before you can start treatment on this study, you will have what are called screening tests. These tests will help the doctor decide if you are eligible to take part in this study. You will have a complete medical history and physical exam. This includes blood tests (about 2 tea spoons), and x-rays. Women who are able to have children must have a negative blood or urine pregnancy test. If you are found to be eligible to take part in this study, you will receive trastuzumab through a vein (IV) every week until the disease gets worse. GM-CSF will be injected under the skin at least once a day until the white blood cell count is stable. GM-CSF will also continue during the course of study until the disease progresses. You will have further evaluation of your disease by computed tomography-CT scan, bone scan, chest X-ray, etc. at 2, 4, 6, 9, 12, 18, and 24 months after the start of treatment. You will have blood tests (about 2 tea spoons) at least twice a week until the appropriate dose of GM-CSF is found. The dose may increase or decrease depending on the blood test. You will have blood (about 2 tablespoons) drawn before treatment at the 2nd and 4th month, and if the disease gets worse. You will be removed from the study if the disease is progressing or severe side effects occur. This is an investigational study. The FDA has approved trastuzumab and GM-CSF, but their use in this study is experimental. A total of 36 patients will take part in this study. All will be enrolled at UT MD Anderson Cancer Center.
Interventions
DRUGHerceptin
4 mg/kg IV Over 90 Minutes
DRUGGM-CSF
250 mcg/m\^2 Subcutaneously
Sponsors
Bayer
M.D. Anderson Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
1. Histological confirmation of invasive carcinoma of the breast. 2. HER-2/neu overexpression: 3+ by immunohistochemical staining or Fluorescence in situ hybridization (FISH) (+). 3. Stage IV breast cancer with measurable disease. 4. Patient receiving progressive disease after Herceptin plus chemotherapy or Herceptin alone. No more than two Herceptin containing regimens. 5. Zubrod performance status 0 or 1. 6. Adequate hematological parameters (White Blood cells-WBC \> 3,000/mm3, platelet count \> 100,000/mm3), adequate renal function (serum creatinine \< 2.0 mg/dl), adequate liver function (total bilirubin, aspartate aminotransferase (AST or SGOT) or alanine aminotransferase (ALT or SGPT) \< 3 x normal).
Exclusion criteria
1. Active Brain metastasis. 2. No measurable disease at the time of registration (e.g. bone only, leptomeningeal disease alone or pleural effusion alone). 3. More than 2 Herceptin containing regimens in metastatic breast cancer. 4. Known history of HIV positive. 5. Chronic active hepatitis or cirrhosis. 6. Symptomatic pulmonary disease. 7. Use of steroid of non-steroidal anti-inflammatory analgesic or Cox-2 inhibitor 1 week prior to registration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Tumor Response (Stable Disease) | 2 months | Number of participants with response defined as stable disease or better using Response Evaluation Criteria In Solid Tumors (RECIST) at the month 2 evaluation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Stable Disease | 6 Years | Stable disease is measured from the start of the treatment until the RECIST criteria for disease progression is met. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period of November 2002 to April 2007, all recruited at University of Texas MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| HER2+ Metastatic Breast Cancer Herceptin 4 mg/kg intravenous (IV) Over 90 Minutes + Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) 250 mcg/m\^2 subcutaneously | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
Baseline characteristics
| Characteristic | HER2+ Metastatic Breast Cancer |
|---|---|
| Age Continuous | 48 years |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 18 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 | 17 / 17 |
| serious Total, serious adverse events | 0 / 17 |
Outcome results
Primary
Number of Participants With Tumor Response (Stable Disease)
Number of participants with response defined as stable disease or better using Response Evaluation Criteria In Solid Tumors (RECIST) at the month 2 evaluation.
Time frame: 2 months
Population: Analysis was per protocol, and of 18 enrolled, one participant was inevaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HER2+ Metastatic Breast Cancer | Number of Participants With Tumor Response (Stable Disease) | 5 participants |
Secondary
Duration of Stable Disease
Stable disease is measured from the start of the treatment until the RECIST criteria for disease progression is met.
Time frame: 6 Years
Population: Analysis was per protocol, and of 18 enrolled, one participant was inevaluable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HER2+ Metastatic Breast Cancer | Duration of Stable Disease | 15.8 weeks |