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A Phase II Study of Preoperative Dose-Dense Chemotherapy With Sequential Doxorubicin and Docetaxel for Initial Treatment of Operable and Inoperable Stage II-IIIB Breast Cancer

Phase 2
18 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

A Phase II Study of Preoperative Dose-Dense Chemotherapy With Sequential Doxorubicin and Docetaxel for Initial Treatment of Operable and Inoperable Stage II-IIIB Breast Cancer

OBJECTIVES: I. Determine the clinical and pathological response of women with stage II-IIIB
primary breast cancer to preoperative high dose chemotherapy with sequential doxorubicin and
docetaxel. II. Determine the safety and toxicity of this regimen in these patients. III.
Determine the rate of breast conservation surgery in these patients on this regimen. IV.
Determine the clinical response of these patients to docetaxel after 3 courses of
doxorubicin. V. Correlate any circulating tumor cells shed at time of surgery with clinical
response and pathological findings in these patients. VI. Determine whether tumor response
correlates with HER2/neu expression of the primary tumor.

OUTLINE: Patients receive doxorubicin IV on days 1, 15, and 29, followed by docetaxel IV
over 1 hour on days 43, 57, and 71. Filgrastim (G-CSF) is administered subcutaneously on
days 3-10 of each 2 week course. Fourteen to 21 days following preoperative chemotherapy,
patients undergo a radical, modified radical, or breast sparing surgery plus axillary lymph
node dissection. Patients with disease progression or inoperable stage IIIB disease are
removed from study. Following surgery, patients are stratified into one of three
postoperative regimens: Stratum I: Patients with 0 lymph node metastases receive no further
chemotherapy or receive cyclophosphamide, methotrexate, and fluorouracil (CMF) for 4
courses. Stratum II: Patients with 1-3 lymph node metastases receive CMF for 4 courses.
Stratum III: Patients with at least 4 lymph node metastases or stage IIIB may receive high
dose chemotherapy with stem cell support. Two to 6 weeks after surgery, patients undergoing
breast sparing procedure receive adjuvant radiotherapy. Patients undergoing mastectomy
receive chest wall and supraclavicular radiotherapy if initial clinical stage is T3, T4, or
N2. All other patients with N1 with greater than 4 lymph nodes and N3 should receive
radiotherapy. Radiotherapy is administered 5 days a week for 5.5 weeks. Patients with
positive estrogen or progesterone receptors receive oral tamoxifen daily for 5 years.
Patients are followed every 3 months for 3 years, then every 6 months for 5 years, and then
annually thereafter.

PROJECTED ACCRUAL: Approximately 27-35 patients will be accrued for this study.

Inclusion Criteria

Eligibility Criteria:

- Women with a diagnosis of breast cancer established by tissue obtained by needle
biopsy or incisional biopsy.

- There must be a residual measurable breast and/or axillary mass after biopsy.

- Clinical stage T1, N1-3, Mo or T2-4, N0-3, Mo. T2N0 lesions < 4cm in maximum
dimension are eligible only if breast conservation is not feasible or practical
without preoperative tumor shrinkage.

- Patients must be willing to undergo a mastectomy or breast sparing procedure plus
axillary lymph node dissection.

- There must be no evidence of systemic metastases.

- No prior chemotherapy. Patients may have received up to 14 days of tamoxifen. 3.1.7
Patients > 18years are eligible.

- ECOG performance status 0-1.

- Normal hematologic function defined as white blood cell count > 3500/111 or
neutrophil count > 1500411 and platelets >100,000/4

- Normal renal function defined as serum creatinine <1.5 mg/di.

- Adequate hepatic function. Bilirubin must be < institutional upper limit of normal
(ULN). Transaminases (SGOT and/or SGPT) may be up to 2.5 X institutional ULN if
alkaline phosphatase is < ULN, or alkaline phosphatase may be up to 4 X ULN if
transaminases are < ULN. However, patients who have both transaminase elevation > 1.5
X ULN and alkaline phosphatase > 2.5 X ULN are not eligible for this study (due to
decreased clearance of docetaxel and increased risk of toxicity).

- Patients with prior CIS of cervix or nonmelanoma skin cancers are eligible. Patients
with prior DCIS or LCIS of breast are eligible if not previously treated with
radiation or chemotherapy. Patients with prior malignancies including contralateral
breast cancers treated with curative intent more than 5 years before enrollment are

- Patients must have signed informed consent.

Exclusion Criteria:

- Patients with a prior history of malignancy other than those mentioned in section
3.1.12 are ineligible.

- Patients must not have severe concurrent medical or psychiatric illness (i.e. no
severe diabetes mellitus, poorly controlled ischemic heart disease or congestive
heart failure, or severe chronic obstructive or restrictive pulmonary disease).

- The interval between initial diagnosis of breast cancer and the start of treatment
must not be greater than 8 weeks.

- Due to anticipated toxicities to an unborn fetus, and excretion of chemotherapy in
breast milk, patients must not be pregnant or lactating and must use effective
contraception during treatment.

- No history of hypersensitivity reaction to preparation containing polysorbate 80,
3.2.6 Patients must not have peripheral neuropathy grade 2 or higher.

- Patients must not have had prior radiation to >25% of bone marrow

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine the clinical response of these patients to treatment

Outcome Description:

A clinical evaluation of tumor size includes repeat measurements of the palpable tumor in 2 dimensions, repeat mammography, if originally informative, of the affected breast with measurements of the palpable tumor in 2 or 3 dimensions and/or, evaluation of ipsilateral axillary lymph nodes with measurements, if palpable.

Outcome Time Frame:

after 3 courses (12 weeks)

Safety Issue:


Principal Investigator

Brenda W. Cooper, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center


United States: Federal Government

Study ID:




Start Date:

February 1999

Completion Date:

January 2013

Related Keywords:

  • Breast Cancer
  • stage II breast cancer
  • stage IIIA breast cancer
  • stage IIIB breast cancer
  • Breast Neoplasms



Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065
Metro Health Medical Center Cleveland, Ohio  44109