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A Randomized Phase III Study Exploring the Efficacy of Capecitabine Given Concomitantly or in Sequence to EC-Doc With or Without Trastuzumab as Neoadjuvant Treatment of Primary Breast Cancer


Phase 3
18 Years
N/A
Open (Enrolling)
Female
Breast Cancer

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Trial Information

A Randomized Phase III Study Exploring the Efficacy of Capecitabine Given Concomitantly or in Sequence to EC-Doc With or Without Trastuzumab as Neoadjuvant Treatment of Primary Breast Cancer


OBJECTIVES:

Primary

- Compare the pathologic complete response rates in women with stage I-III primary breast
cancer treated with neoadjuvant epirubicin hydrochloride, cyclophosphamide, and
docetaxel with versus without capecitabine followed by surgery .

- Compare the pathologic complete response rates in women with HER-2/neu-positive tumors
receiving trastuzumab (Herceptin®) simultaneously with neoadjuvant epirubicin
hydrochloride, cyclophosphamide, and docetaxel to women with HER-2/neu-negative tumors
receiving neoadjuvant chemotherapy only.

Secondary

- Determine the toxicity of these regimens in these patients.

- Determine the disease-free (loco-regional and distant) survival and overall survival of
patients treated with these regimens.

- Determine the disease-free (loco-regional and distant) survival and overall survival of
patients treated with or without trastuzumab.

- Determine the breast conservation rate in patients treated with these regimens.

- Determine the frequency of the use of sentinel node biopsy for selecting patients for
neoadjuvant chemotherapy.

- Compare the frequency of sentinel node biopsies at surgery after neoadjuvant
chemotherapy in each arm.

- Determine the pathologic complete response rates to each regimen in the subgroup of
patients with locally advanced (T4a-d, N0-3, M0) breast cancer.

- Determine the response rate (complete response, partial response, or no change) at
surgery (by imaging methods and by histopathological exam) in patient subgroups
according to their response after four treatments with epirubicin hydrochloride and
cyclophosphamide.

- Determine the intention for the use of neoadjuvant chemotherapy, in terms of freedom
from disease, avoiding mastectomy, improving breast conservation, and gaining
information about efficacy.

OUTLINE: This is a randomized, controlled, open-label, multicenter study. Patients are
stratified according to participating site, clinical response after 4 courses of epirubicin
hydrochloride and cyclophosphamide (complete response vs partial response vs no change),
HER-2/neu-status (negative vs 3+ by immunohistochemistry [IHC] or positive by fluorescence
in situ hybridization [FISH]), estrogen receptor (ER)/progesterone receptor (PR) status (ER
or PR positive vs ER and PR negative), and extent of disease (T4 or N3 vs T1-3 and N0-2).

All patients receive epirubicin hydrochloride IV over 30-60 minutes and cyclophosphamide IV
over 60 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of
disease progression or unacceptable toxicity. Patients are then randomized to 1 of 3
treatment arms.

- Arm I: Patients receive docetaxel IV over 60 minutes on day 1. Treatment repeats every
21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

- Arm II: Patients receive docetaxel as in arm I. Patients also receive oral capecitabine
twice daily on days 1-14. Treatment with docetaxel and capecitabine repeats every 21
days for 4 courses in the absence of disease progression or unacceptable toxicity.

- Arm III: Patients receive docetaxel as in arm I. Patients then receive oral
capecitabine twice daily on days 1-14. Treatment with capecitabine repeats every 21
days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients with HER-2/neu-positive tumors also receive trastuzumab (Herceptin®) IV over 90
minutes on day 1 of each course of chemotherapy (during treatment with epirubicin
hydrochloride and cyclophosphamide AND during randomized treatment).

Within 2 weeks after completion of chemotherapy, all patients undergo surgery. Within 2
weeks after surgery, patients with HER-2/neu-positive tumors resume trastuzumab treatment
for up to 1 year.

After completion of study treatment, patients are followed periodically for at least 5
years.

PROJECTED ACCRUAL: A total of 1,500 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed unilateral or bilateral primary breast cancer

- Meets 1 of the following staging criteria:

- Clinical stage T4 or T3 disease

- Clinical stage T1 and pathologic stage N+ by sentinel lymph node biopsy OR
clinical stage T2, N+ disease AND estrogen receptor (ER) or progesterone
receptor (PR) positive tumor

- ER and PR negative tumor (T1-4, N0-3, M0)

- Disease confirmed by core biopsy

- No fine-needle aspiration or incisional biopsy

- Bidimensionally measurable disease*

- Tumor lesion palpable and measures ≥ 2 cm OR tumor lesion ≥ 1 cm in maximum
diameter by sonography

- For inflammatory disease, extent of inflammation can be used as measurable
lesion NOTE: *In patients with multifocal or multicentric breast cancer,
the largest lesion should be measured

- Candidate for adjuvant chemotherapy

- No low- or moderate-risk patients who are doubtful candidates for adjuvant
chemotherapy and do not fulfill the staging criteria

- Known HER-2/neu status by core biopsy

- HER-2/neu positive tumor is defined as +3 by immunohistochemistry [IHC] OR
positive by fluorescence in situ hybridization (FISH)

- No evidence of distant metastasis

- Hormone receptor status:

- ER- or PR-positive tumor OR ER- and PR-negative tumor

PATIENT CHARACTERISTICS:

- No male patients

- Menopausal status not specified

- Karnofsky performance status 80-100%

- Life expectancy ≥ 10 years (disregarding diagnosis of cancer)

- Normal cardiac function confirmed by ECG

- LVEF ≥ 55% by cardiac ultrasound

- Neutrophil count ≥ 2,000/mm^3

- Platelet count ≥ 100,000/mm^3

- Hemoglobin ≥ 10 g/dL

- Bilirubin normal

- AST and ALT ≤ 2.5 times upper limit of normal (ULN)

- Alkaline phosphatase (AP) ≤ 5 times ULN OR

- AP ≤ 2.5 times ULN AND AST and/or ALT ≤ 1.5 times ULN

- Creatinine ≤ 2 mg/dL

- Creatinine clearance ≥ 50 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective nonhormonal contraception

- No motor or sensory neuropathy ≥ grade 2

- No other malignancy within the past 5 years except carcinoma in situ of the cervix or
nonmelanoma skin cancer

- No New York Heart Association class II-IV congestive heart failure

- No coronary artery disease

- No history of myocardial infarction

- No uncontrolled arterial hypertension (i.e., blood pressure ≥ 160/90 mm Hg despite
antihypertensive therapy)

- No rhythm abnormalities requiring permanent therapy

- No history of significant neurological or psychiatric disorders including psychotic
disorders, dementia, or seizures that would preclude giving informed consent

- No active infection

- No active peptic ulcer

- No unstable diabetes mellitus or insulin-dependent type II diabetes mellitus

- No other serious illness or medical condition

- No known hypersensitivity reaction to investigational compounds or incorporated
substances

- No definite contraindications for the use of corticosteroids

- No known dihydropyrimidine dehydrogenase deficiency

- Must be fit for anthracycline/taxane-containing chemotherapy

PRIOR CONCURRENT THERAPY:

- No prior chemotherapy for any malignancy

- No prior radiation therapy for breast cancer

- No concurrent bisphosphonates during chemotherapy

- Bisphosphonates allowed postoperatively

- No chronic treatment with corticosteroids unless it is initiated > 6 months prior to
study entry and is given at low doses (≤ 20 mg methylprednisolone or equivalent)

- No concurrent amifostine during chemotherapy

- No concurrent cardioprotectors (e.g., dexrazoxane) during chemotherapy

- No concurrent sex hormone therapy

- No concurrent virostatic agents (e.g., sorivudine or brivudine)

- No concurrent aminoglycosides

- No other concurrent experimental drugs or anticancer therapy

- At least 30 days since prior participation in another clinical trial with any
investigational (not marketed) drug

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pathologic complete response

Safety Issue:

No

Principal Investigator

Gunter von Minckwitz, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

German Breast Group

Authority:

Unspecified

Study ID:

CDR0000455125

NCT ID:

NCT00288002

Start Date:

January 2005

Completion Date:

Related Keywords:

  • Breast Cancer
  • inflammatory breast cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • stage IIIC breast cancer
  • stage IA breast cancer
  • stage IB breast cancer
  • estrogen receptor-negative breast cancer
  • estrogen receptor-positive breast cancer
  • HER2-negative breast cancer
  • HER2-positive breast cancer
  • Breast Neoplasms

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