Breast Cancer
Conditions
Keywords
inflammatory breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer
Brief summary
RATIONALE: Dose-dense scheduling with (peg)filgrastim support may improve the clinical and pathologic complete response rate (pCR) and safety profile of single agent neoadjuvant docetaxel therapy. PURPOSE: To evaluate whether dose-dense scheduling with (peg)filgrastim support may improve the clinical and pathologic complete response rate (pCR) and safety profile of single agent neoadjuvant docetaxel therapy. To determine the changes in molecular markers that occurs with single agent docetaxel, tissue will be obtained at the end of the four cycles of docetaxel (either by repeat biopsy or definitive surgery).
Detailed description
OBJECTIVES: Primary * Pathologic complete response rate (pCR) of dose dense docetaxel in the neoadjuvant setting. Secondary * Safety and toxic effects of this regimen in these patients. * Tumor response rate (as measured by ultrasound) in patients treated with this regimen. * Determine whether early changes in markers of cell cycle position, proliferation, or apoptosis correlate with pathologic complete response rate in these patients. * Determine whether the molecular profile that predicts for chemoresponsiveness also predicts for response to radiotherapy (as measured by local recurrence) in these patients. * Determine whether tumors that demonstrate the greatest degree of change in protein expression patterns from pre- to post-docetaxel treatment will also be those that are most sensitive to chemotherapy (as measured by pathologic response rate) in these patients. OUTLINE: This is a nonrandomized, open-label, pilot study. * Tissue Collection: Patients undergo tumor core biopsy (6-8 cores) and blood collection prior to initiating neoadjuvant docetaxel. * Neoadjuvant docetaxel with hematopoietic support: Patients receive docetaxel IV over 1 hour on day 1. Patients also receive pegfilgrastim subcutaneously (SC) on day 1 or 2 of each course OR filgrastim (G-CSF) or sargramostim (GM-CSF) SC daily beginning between day 2-4 of each course and continuing until blood counts recover. Treatment repeats every 14 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. * Surgery: Within 4-6 weeks after completion of neoadjuvant docetaxel, patients undergo definitive surgery. Patients undergo tumor biopsy and blood collection periodically for pharmacokinetic, genetic, and molecular biomarker correlative studies. Samples are examined for changes in p21 protein expression (and/or p21 phosphorylation) and the protein expression profile. After completion of study treatment, patients are followed at least every 6 months for 3 years and then annually thereafter. PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
Interventions
DRUGdocetaxel
Docetaxel 75 mg/m2 IV (1-hour infusion) on day 1 of each cycle (cycle = 2 weeks) x 4 cycles
GENETICprotein expression analysis
protein expression analysis
OTHERlaboratory biomarker analysis
laboratory biomarker analysis
PROCEDUREbiopsy
biopsy
PROCEDUREconventional surgery
conventional surgery
PROCEDUREneoadjuvant therapy
neoadjuvant therapy
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
NON_RANDOMIZED
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: Inclusion: * Histologically or cytologically confirmed invasive carcinoma of the breast by core biopsy * Tumor ≥ 2 cm in greatest dimension(may be either node positive or node negative disease * Patients with non-metastatic breast cancer who are in the judgment of the treating medical oncologist considered to be of sufficiently high risk to warrant adjuvant chemotherapy * Patients with internal mammary, supraclavicular and/or axillary node involvement are eligible. Patients with inflammatory breast cancer are eligible * Patients with T0 disease but palpable and measurable adenopathy are eligible for this trial. All sites of disease should be noted and followed * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Menopausal status not specified * Female ≥ 18 years old * Absolute neutrophil count ≥ 1,000/mm\^3 * Hemoglobin ≥ 8 g/dL * Platelet count ≥ 100,000/mm\^3 * Creatinine ≤ 1.5 times upper limit of normal (ULN) * Bilirubin normal * Alkaline phosphatase (AP), AST, and ALT meeting 1 of the following criteria: * AP normal AND AST or ALT ≤ 5 times ULN * AP ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN * AP ≤ 5 times ULN AND AST or ALT normal * Women of child-bearing potential, must have a negative serum pregnancy test and must use effective contraception for the duration of the study and for at least 6 months after completion of study treatment * Patients with prior malignancies are eligible if they have been disease free for ≥ 5 years. Patients with curative treatment of non-melanomatous skin cancer, carcinoma in situ of the cervix, contralateral DCIS treated with mastectomy are eligible even if it is diagnosed in \< 5 years. PRIOR CONCURRENT THERAPY: * No prior anthracycline or taxane-based chemotherapy. Patients who received chemoprevention are eligible if the chemopreventive agent has been discontinued for at least one year prior to enrollment in the current study. * At least 1 year since prior tamoxifen for breast cancer prevention Exclusion: * Prior radiotherapy to the ipsilateral breast * Patients who have had radiation to the contralateral breast are eligible * Evidence of distant metastatic disease (i.e., lung, liver, bone, brain) * Pregnant of breastfeeding * Patients who have congestive heart failure, angina pectoris, uncontrolled cardiac arrhythmia, or other significant heart disease, or who have had a myocardial infarction within the past year * Patients with \> grade 1 peripheral neuropathy * Patients with a history of hypersensitivity reaction to products containing polysorbate 80 (Tween 80) * Patients receiving an investigational anticancer drug within 3 weeks of registration * Patients with serious medical illness that in the judgment of the treating physician, places the patient at risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number Participants to Achieve Pathologic Complete Response | 3 month | whether or not patient has pathologic complete response (pCR) to dose dense docetaxel in the neoadjuvant setting (pCR = no residual viable tumor on histologic analysis) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Profile Based on Number of Patients With Each Worst-grade Toxicity | Through 30 days after completion of treatment | Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables. Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1, least severe; to grade 5, most severe) following NCI Common Toxicity Criteria |
| Tumor Response as Measured by Ultrasound | At screening, 8 weeks and at surgery (within 14-21 days) | Progressive disease (PD): \>=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): \>=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. |
Countries
United States
Participant flow
Recruitment details
This study enrolled patients from February 2004 to September 2007.
Pre-assignment details
A total of 39 people were consented, one of which was ineligible. Four patients withdrew from the study before beginning treatment.
Participants by arm
| Arm | Count |
|---|---|
| Therapeutic Intervention Docetaxel 75 mg/m2 IV (1-hour infusion) on day 1 of each cycle (cycle = 2 weeks) x 4 cycles | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Therapeutic Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants |
| Age Continuous | 47 years STANDARD_DEVIATION 1 |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 34 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 | 27 / 32 |
| serious Total, serious adverse events | 9 / 32 |
Outcome results
Primary
Number Participants to Achieve Pathologic Complete Response
whether or not patient has pathologic complete response (pCR) to dose dense docetaxel in the neoadjuvant setting (pCR = no residual viable tumor on histologic analysis)
Time frame: 3 month
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Therapeutic Intervention | Number Participants to Achieve Pathologic Complete Response | pCR: Yes | 5 participants |
| Therapeutic Intervention | Number Participants to Achieve Pathologic Complete Response | pCR: No | 29 participants |
Secondary
Safety Profile Based on Number of Patients With Each Worst-grade Toxicity
Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables. Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1, least severe; to grade 5, most severe) following NCI Common Toxicity Criteria
Time frame: Through 30 days after completion of treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Therapeutic Intervention | Safety Profile Based on Number of Patients With Each Worst-grade Toxicity | No. patients with worst-grade toxicity 1 | 5 participants |
| Therapeutic Intervention | Safety Profile Based on Number of Patients With Each Worst-grade Toxicity | No. patients with worst-grade toxicity 2 | 8 participants |
| Therapeutic Intervention | Safety Profile Based on Number of Patients With Each Worst-grade Toxicity | No. patients with worst-grade toxicity 3 | 11 participants |
| Therapeutic Intervention | Safety Profile Based on Number of Patients With Each Worst-grade Toxicity | No. patients with worst-grade toxicity 4 | 1 participants |
| Therapeutic Intervention | Safety Profile Based on Number of Patients With Each Worst-grade Toxicity | No. patients with worst-grade toxicity 5 | 0 participants |
Secondary
Tumor Response as Measured by Ultrasound
Progressive disease (PD): \>=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started. Complete response (CR): disappearance of all target lesions. Partial response (PR): \>=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD. Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD.
Time frame: At screening, 8 weeks and at surgery (within 14-21 days)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Therapeutic Intervention | Tumor Response as Measured by Ultrasound | Complete Response | 5 participants |
| Therapeutic Intervention | Tumor Response as Measured by Ultrasound | Progressive Disease | 1 participants |
| Therapeutic Intervention | Tumor Response as Measured by Ultrasound | Stable Disease | 1 participants |
| Therapeutic Intervention | Tumor Response as Measured by Ultrasound | Partial Response | 11 participants |