A Phase I/II Study Of Increasing Doses Of Epirubicin And Docetaxel Plus Pegfilgrastim For Locally Advanced Or Inflammatory Breast Cancer
16 Years
N/A
Female
Breast Cancer
Trial Information
A Phase I/II Study Of Increasing Doses Of Epirubicin And Docetaxel Plus Pegfilgrastim For Locally Advanced Or Inflammatory Breast Cancer
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Toxic effects
Outcome Description:
Findings were presented at ASCO 2010
Outcome Time Frame:
7 years
Safety Issue:
Yes
Principal Investigator
Maureen E. Trudeau, BSc, MA, MD, FRCPC
Investigator Role:
Study Chair
Investigator Affiliation:
Edmond Odette Cancer Centre at Sunnybrook
Authority:
Canada: Health Canada
Study ID:
MA22
NCT ID:
NCT00066443
Start Date:
February 2003
Completion Date:
June 2014
Related Keywords:
- Breast Cancer
- stage IIIA breast cancer
- stage IIIB breast cancer
- stage IIIC breast cancer
- inflammatory breast cancer
- Breast Neoplasms
- Inflammatory Breast Neoplasms
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