Breast Cancer
Conditions
Keywords
stage IV breast cancer, recurrent breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Colony-stimulating factors, such as filgrastim, may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab with docetaxel, vinorelbine, and filgrastim in treating women who have stage IV breast cancer.
Detailed description
OBJECTIVES: * Determine the 1-year survival of women with HER2-positive stage IV breast cancer treated with trastuzumab (Herceptin), docetaxel, and vinorelbine with filgrastim (G-CSF) support. * Determine the response rate (complete and partial, confirmed and unconfirmed) in the subset of patients with measurable disease treated with this regimen. * Determine the progression-free survival of patients treated with this regimen. * Determine the qualitative and quantitative toxic effects of this regimen in these patients. * Obtain tissue blocks for the determination of predictors of response (e.g., beta-tubulin mutations) to microtubule interacting agents in this patient population and for other future studies. OUTLINE: This is a pilot, multicenter study. Patients receive docetaxel IV over 1 hour on day 1, filgrastim (G-CSF) subcutaneously on days 2-21, vinorelbine IV over 6-10 minutes on days 8 and 15, and trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. If docetaxel and vinorelbine are discontinued due to unacceptable toxicity, patients may continue to receive trastuzumab. If trastuzumab is discontinued due to unacceptable toxicity, patients may continue to receive chemotherapy with G-CSF support. Patients are followed every 6 months for 3 years. PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study within 18-22.5 months.
Interventions
BIOLOGICALfilgrastim
BIOLOGICALtrastuzumab
DRUGdocetaxel
DRUGvinorelbine
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
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
DISEASE CHARACTERISTICS: * Histologically confirmed stage IV breast cancer * Metastasis to the ipsilateral supraclavicular lymph nodes allowed * HER2-positive by fluorescence in situ hybridization (FISH) or immunohistochemistry 3+ staining confirmed in the adjuvant or metastatic setting * No effusions or ascites as only sites of disease * No primary or metastatic brain or central nervous system tumor * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age: * 18 and over Sex: * Female Menopausal status: * Not specified Performance status: * Zubrod 0-2 Life expectancy: * Not specified Hematopoietic: * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic: * Bilirubin normal * aspartate aminotransferase or Alanine aminotranferease no greater than 1.5 times upper limit of normal (ULN) * Alkaline phosphatase no greater than 2.5 times ULN Renal: * Not specified Cardiovascular: * left ventricular ejection fraction normal by multigated radionuclide angiography or echocardiogram (patients who have received prior anthracycline therapy) * No clinical evidence or history of cardiomyopathy Other: * No pre-existing grade 2 or greater motor or sensory peripheral neuropathy except abnormalities due to cancer * No prior severe hypersensitivity reaction to docetaxel or other drugs formulated with Polysorbate 80 * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or other adequately treated stage I or II cancer currently in complete remission * No known sensitivity to E. coli-derived proteins * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * At least 6 months since prior chemotherapy * Prior anthracycline as adjuvant therapy allowed * No prior cumulative dose of doxorubicin more than 360 mg/m\^2 * No prior cumulative dose of epirubicin more than 720 mg/m\^2 * No more than 1 prior adjuvant or neoadjuvant chemotherapy regimen for primary disease * No prior docetaxel * No prior vinorelbine * Prior paclitaxel allowed Endocrine therapy: * Prior hormonal therapy as adjuvant therapy or for metastatic breast cancer allowed * No concurrent hormonal therapy Radiotherapy: * At least 3 weeks since prior radiotherapy Surgery: * At least 2 weeks since prior surgery and recovered
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Survival at 1 Year | 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Complete and Partial, Confirmed and Unconfirmed) | response assessed after every 3 cycles (9 weeks) during treatment for up to 3 years if no progession | Response was measured by the RECIST criteria. A patient was considered a responder if there was confirmed or unconfirmed partial or complete response. All others were considered non-responders even if the patient was technically not assessable due to different measurement techniques at the two time points. |
| Progression-free Survival | 2 years | — |
| Toxicity | toxicities assessed every 3 weeks during treatment, for up to 3 years if no progession | Number of patients for whom highest grade of toxicity observed during treatment. Only adverse events that are possibly, probably or definitely related to study drug are reported. |
Countries
United States
Participant flow
Recruitment details
During the period February 2003 to December 2006, 76 patients were enrolled at 28 SWOG institutions.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim Trastuzumab, docetaxel, vinorelbine and filgrastim
docetaxel : 60 mg/m\^2 on Day 1 of 21-day cycles
vinorelbine : 27.5 mg/m\^2 on Days 8 and 15
filgrastim : 5 microg/kg/day on Days 2 to 21
trastuzumab : 4 mg/kg by IV over a 90-minute period on Day 1 of the first cycle, then weekly 2 mg/kg by IV over a 30-minute period | 74 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 20 |
| Overall Study | Ineligible | 2 |
| Overall Study | Other reasons | 23 |
| Overall Study | Patient refusal | 12 |
| Overall Study | Progression | 19 |
Baseline characteristics
| Characteristic | Trastuzumab, Docetaxel, Vinorelbine and Filgrastim |
|---|---|
| Age, Customized 30-39 | 11 participants |
| Age, Customized 40-49 | 26 participants |
| Age, Customized 50-59 | 19 participants |
| Age, Customized 60-69 | 15 participants |
| Age, Customized 70-79 | 3 participants |
| Sex: Female, Male Female | 74 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 | 71 / 73 |
| serious Total, serious adverse events | 0 / 73 |
Outcome results
Primary
Survival at 1 Year
Time frame: 1 year
Population: All eligible patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Survival at 1 Year | 93 percentage of patients |
Secondary
Progression-free Survival
Time frame: 2 years
Population: All eligible patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Progression-free Survival | 20 months |
Secondary
Response Rate (Complete and Partial, Confirmed and Unconfirmed)
Response was measured by the RECIST criteria. A patient was considered a responder if there was confirmed or unconfirmed partial or complete response. All others were considered non-responders even if the patient was technically not assessable due to different measurement techniques at the two time points.
Time frame: response assessed after every 3 cycles (9 weeks) during treatment for up to 3 years if no progession
Population: patients with Response Evaluation Criteria in Solid Tumors measurable disease
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Response Rate (Complete and Partial, Confirmed and Unconfirmed) | 53 participants |
Secondary
Toxicity
Number of patients for whom highest grade of toxicity observed during treatment. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time frame: toxicities assessed every 3 weeks during treatment, for up to 3 years if no progession
Population: Eligible patients
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | SGPT (ALT) increase | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Sensory neuropathy | 5 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Syncope | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Respiratory infection, unk ANC | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Alkaline phosphatase increase | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Anemia | 7 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Arthralgia | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Bone pain | 2 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Catheter related infection | 2 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Chest pain,not cardio or pleur | 2 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Dehydration | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Depression | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Diarrhea without colostomy | 2 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Dyspepsia/heartburn | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Dyspnea | 2 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Fatigue/malaise/lethargy | 9 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Febrile neutropenia | 4 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Headache | 3 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Hyperglycemia | 6 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Hypermagnesemia | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Hypokalemia | 2 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Hypophosphatemia | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Hypotension | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Hypoxia | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Infection w/o 3-4 neutropenia | 4 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Infection with 3-4 neutropenia | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | LVEF decrease/CHF | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Leukopenia | 11 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Lymphopenia | 2 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Muscle weakness (not neuro) | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Nausea | 3 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Neutropenia/granulocytopenia | 16 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | PRBC transfusion | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Pain-other | 3 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Pericar. effusion/pericarditis | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Pneumonitis/infiltrates | 3 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Respiratory infect w/ neutrop | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Tearing | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Thrombosis/embolism | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Transplant-pRBC transfusion | 1 Participants |
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | Toxicity | Vomiting | 2 Participants |