Epirubicin, Docetaxel, and Pegfilgrastim in Treating Women With Locally Advanced or Inflammatory Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy such as epirubicin and docetaxel use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as pegfilgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy. PURPOSE: Phase I/II trial to study the effectiveness of combining epirubicin and docetaxel with pegfilgrastim in treating women who have locally advanced or inflammatory breast cancer.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose and recommended phase II dose of docetaxel and epirubicin when given with pegfilgrastim in women with locally advanced or inflammatory breast cancer. (Phase I, group 1 closed to accrual as of 9/13/04 and Phase II, group 1 closed to accrual as of 5/10/06) Determine the toxicity of this regimen in these patients. Determine the clinical and pathological response rate and duration of response in patients treated with this regimen. Determine drug sensitivity and resistance in patients treated with this regimen. Determine prognostic and predictive markers in patients treated with this regimen. OUTLINE: This is a nonrandomized, multicenter, dose-escalation study of docetaxel and epirubicin. Phase I: Group 1 (21-day regimen) (closed to accrual as of 09/13/04): Patients receive epirubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 1 and pegfilgrastim subcutaneously on day 2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with objective response after 6 courses may receive additional therapy at the discretion of the physician. Group 2 (14-day regimen): Patients receive epirubicin IV over 15 minutes and docetaxel IV over 60 minutes on day 1 and pegfilgrastim subcutaneously on day 2. Treatment repeats every 14 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients with objective response after 8 courses may receive additional therapy at the discretion of the physician. Cohorts of 3-6 patients receive escalating doses of epirubicin and docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Phase II: Group 1 (21-day regimen) (closed to accrual as of 5/10/06): Patients receive treatment as in phase I with epirubicin and docetaxel at the recommended Phase II dose. Group 2 (14-day regimen): Patients receive treatment as in phase I with epirubicin and docetaxel at the recommended Phase II dose. Patients are followed at 1 month, every 3 months for 1 year, every 6 months for 1 year, and then annually thereafter. PROJECTED ACCRUAL: Approximately 90 patients will be accrued for this study.

Official Title
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A Phase I/II Study Of Increasing Doses Of Epirubicin And Docetaxel Plus Pegfilgrastim For Locally Advanced Or Inflammatory Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: pegfilgrastim
* Drug: docetaxel
* Drug: epirubicin hydrochloride


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed invasive adenocarcinoma of the breast, meeting any of the following criteria: T4, NX, M0 Any T, N2-N3, M0 Inflammatory breast cancer (redness over at least one-third of the breast), M0 No evidence of metastatic disease by chest x-ray, abdominal ultrasound or CT scan and bone scan Diagnosed within the past 8 weeks Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age 16 and over Sex Female Menopausal status Not specified Performance status ECOG 0-2 Life expectancy Not specified Hematopoietic Absolute granulocyte count at least 2,000/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL Hepatic Bilirubin less than upper limit of normal (ULN) Must meet criteria for 1 of the following: ALT and AST no greater than 1.5 times ULN AND alkaline phosphatase no greater than 2.5 times ULN ALT and AST normal AND alkaline phosphatase no greater than 5 times ULN Renal Creatinine no greater than 1.5 times ULN Cardiovascular Resting LVEF normal by MUGA or echocardiogram No congestive heart failure No angina pectoris No myocardial infarction within the past year No uncontrolled hypertension No uncontrolled arrhythmias Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective non-hormonal contraception No other malignancy within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix No symptomatic peripheral neuropathy grade 2 or greater No active infection No history of significant neurological or psychiatric disorders, including dementia or seizures No peptic ulcer No unstable diabetes mellitus No contraindication to dexamethasone No known sensitivity to E. coli-derived or polyethylene glycol products Willing to undergo core biopsies once prior to registration and core biopsies at 2 other timepoints while on study Geographically accessible for treatment and follow-up PRIOR CONCURRENT THERAPY: Biologic therapy No prior immunotherapy for breast cancer Chemotherapy No prior chemotherapy for breast cancer Endocrine therapy No prior hormonal therapy for breast cancer No concurrent corticosteroids except for premedication or hypersensitivity reaction No concurrent oral contraception Radiotherapy No prior radiotherapy for breast cancer Surgery No prior surgery for breast cancer other than biopsy Other No prior systemic therapy for breast cancer No other concurrent investigational drugs or anticancer treatment No concurrent preventative IV antibiotics

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pegfilgrastim, docetaxel and epirubicin<br> | Biological: pegfilgrastim<br>* Dose escalation schedule A&B = 6mg fixed dose once per cycle on day 2<br>Drug: docetaxel<br>* Dose Escalation schedule A = 75-85 mg/m2 Dose Escalation schedule B = 50-75 mg/m2<br>Drug: epirubicin hydrochloride<br>* Dose escalation schedule A = 75-120 mg/m2 IV Dose escalation schedule B = 50-90 mg/m2 IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxic effects | Findings were presented at ASCO 2010 | 7 years | 
| Response (phase II) | Response was presented at ASCO 2010. Duration of response will be analyzed in 2015 | 12 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, inflammatory breast cancer