HER-2 Positive Metastatic Breast Cancer
Conditions
Keywords
Her2 Positive, Breast Cancer, Metastatic
Brief summary
This study is for women and men who have previously treated metastatic (has spread to other parts in the body), Her2- positive breast cancer. The purpose of this study is to find out what effects (good and bad) the FDA-approved drugs etoposide and trastuzumab have on this type of breast cancer and to determine if these drugs are safe to use together. This research is being done to find more effective treatment for this type of condition. In this study, trastuzumab and etoposide will be given by intravenous infusion (IV; through a vein) on the first 3 days of every 3-week cycle. This is repeated for 6 cycles. After 6 cycles, only trastuzumab will be given until worsening of disease. In this study, a small amount of your tissue that was collected when you had surgery will be evaluated in the lab to look at genetic differences among people and how those differences may affect a response to a specific drug or medicine. This testing will look for a gene called Top2A. Previous studies suggest that people who have both the Top2A and Her2 genes respond to certain chemotherapies (anti-cancer drugs) differently from those who only have the Her2 gene.
Interventions
DRUGEtoposide
etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles
DRUGTrastuzumab
intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease
Sponsors
Genentech, Inc.
Medstar Health Research Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Females or males with histologic confirmation of breast carcinoma and diagnosis of metastatic breast adenocarcinoma * Confirmed HER2 amplification by immunohistochemical staining (IHC) 3+ or FISH amplified (either primary or metastatic). * Have had any number of prior HER2 targeted therapy containing chemotherapies for treatment of breast cancer * Measurable extent of disease * Life expectancy of 3 months or greater * Patients must have adequate heart function, determined with ECHO or MUGA (ECHO preferred). * Patients must have adequate bone marrow and organ function * Patient of childbearing potential must be willing to use an effective means of contraception during their participation on trial * Greater than 3 weeks from prior radiation or chemotherapy; more than 1 week from prior hormonal therapy; and more than 6 weeks from prior treatment with nitrosoureas or mitomycin. * No serious intercurrent medical illness. * Controlled metastatic CNS disease ≥ 3 months * The ability to understand and willingness to sign a written informed consent form, and to comply with the protocol.
Exclusion criteria
* Pregnant or nursing women * Patients who are poor medical risk because of other non-malignant systemic disease or active, uncontrolled infection. * Prior craniospinal radiation, or total body irradiation (TBI). * Patients receiving G-CSF (filgrastim or pegfilgrastim) or thrombopoietin (or other platelet growth factors) within the 3 weeks prior to enrollment (erythropoietin is allowed). * Prior chemotherapy within the last 3 weeks (last 6 weeks for nitrosureas/mitomycin). * Prior radiation therapy within the last 3 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation). * Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. * Current symptoms of angina or uncontrolled arrhythmias, uncontrolled hypertension with systolic blood pressure \>=170 or diastolic blood pressure \>=110. * Psychiatric illness precluding participation in study * Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest. * Carcinomatous meningitis or CNS mets not controlled for ≥ 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Determine ORR of Trastuzumab Combined With Etoposide in Patients With HER2 Positive Metastatic Breast Cancer, and to Assess Toxicity of the Combination of Trastuzumab With Intravenous Etoposide. | The best overall response is the best response recorded from the start of first treatment until the date of first progression or date of death from any cause whichever came first, assessed up to 24 months | To determine the overall response rate |
| To Determine Efficacy of Trastuzumab Combined With Etoposide in Patients With HER2-positive Metastatic Breast Cancer, and to Assess Toxicity of the Combination of Trastuzumab With Intravenous Etoposide. | From the start of first treatment until unacceptable toxicity or date of death, whichever came first, over 24 months | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine Duration of Response | Stable disease is measured from the start of the treatment until the criteria for progression are met, assessed by CT scans at a minimum interval of 8 weeks over 5 years | Stable disease |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single Arm Study Etoposide 100mg/m2 daily x 3 days Q3W and Trastuzumab 8mg/kg loading dose then 6mg/kg, then single agent until disease progression
Etoposide: etoposide 100 mg/m2 daily for 3 days every three weeks for 6 cycles
Trastuzumab: intravenous trastuzumab 8 mg/kg loading dose and then 6 mg/kg every three weeks and then single agent trastuzumab until progression of disease | 2 |
| Total | 2 |
Baseline characteristics
| Characteristic | Single Arm Study |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Region of Enrollment United States | 2 participants |
| Sex: Female, Male Female | 2 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 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
To Determine Efficacy of Trastuzumab Combined With Etoposide in Patients With HER2-positive Metastatic Breast Cancer, and to Assess Toxicity of the Combination of Trastuzumab With Intravenous Etoposide.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: From the start of first treatment until unacceptable toxicity or date of death, whichever came first, over 24 months
Population: Study was terminated and no results were collected.
Primary
To Determine ORR of Trastuzumab Combined With Etoposide in Patients With HER2 Positive Metastatic Breast Cancer, and to Assess Toxicity of the Combination of Trastuzumab With Intravenous Etoposide.
To determine the overall response rate
Time frame: The best overall response is the best response recorded from the start of first treatment until the date of first progression or date of death from any cause whichever came first, assessed up to 24 months
Population: Study was terminated and no results were collected.
Secondary
Determine Duration of Response
Stable disease
Time frame: Stable disease is measured from the start of the treatment until the criteria for progression are met, assessed by CT scans at a minimum interval of 8 weeks over 5 years
Population: Study was terminated and no results were collected.
Secondary
Determine Duration of Response
Time to disease progression
Time frame: Time to disease progression is defined as time from registration date to the date of documented disease progression or death on study, whichever occurs first for 5 years
Population: Study was terminated and no results were collected.
Secondary
Determine Duration of Response
The duration of overall response will be measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started. The duration of overall CR is measured from the time measurements are met for CR until the first date that recurrent disease is objectively documented
Time frame: The progression-free survival rate is defined as the percentage of patients who are without disease progression while on the study treatment at the end of study, over 5 years
Population: Study was terminated and no results were collected.