Chemotherapy Followed by Surgery in Treating Women With Stage II or Stage III Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00003953
First received: November 1, 1999
Last updated: January 25, 2013
Last verified: January 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase II trial to study the effectiveness of doxorubicin and docetaxel followed by surgery in treating women who have stage II or stage III breast cancer.


Condition Intervention Phase
Breast Cancer
Biological: filgrastim
Drug: CMF regimen
Drug: docetaxel
Drug: doxorubicin hydrochloride
Drug: tamoxifen citrate
Procedure: autologous bone marrow transplantation
Procedure: surgical procedure
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Determine the clinical response of these patients to treatment [ Time Frame: after 3 courses (12 weeks) ] [ Designated as safety issue: No ]
    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.

  • Pathological Response [ Time Frame: after surgery at 15 weeks ] [ Designated as safety issue: No ]
    Number of patients with a complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). CR is defined as disappearance of lesions. PR is defined as at least a 50% reduction in the sum of lesions. SD is defined as no significant change and PD is defined as the increase in the size of lesions.


Secondary Outcome Measures:
  • Detection of circulating tumor cells [ Time Frame: after surgery at 15 weeks ] [ Designated as safety issue: No ]
    Detection of circulating tumor cells will be done using a panel of immunocytochemical antibodies directed against breast cancer epithelial cells and IMPATH/BIS laboratories. This assay can detect as few as 1 in 5x105 circulating tumor cells

  • Tumor response correlates with HER2/neu expression of the primary tumor. [ Time Frame: baseline ] [ Designated as safety issue: No ]
    Pretreatment core needle biopsies will be analyzed for expression of HER2/neu expression using immunohistochemical staining.


Enrollment: 39
Study Start Date: February 1999
Study Completion Date: January 2013
Primary Completion Date: November 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Doxorubicin and Docetaxel Biological: filgrastim
Filgrastim (G-CSF) is administered subcutaneously on days 3-10 of each 2 week course.
Drug: CMF regimen
Stratum I and II: receive cyclophosphamide, methotrexate, and fluorouracil (CMF) for 4 courses
Other Names:
  • cyclophosphamide
  • methotrexate
  • fluorouracil
Drug: docetaxel
Docetaxel IV over 1 hour on days 43, 57, and 71.
Drug: doxorubicin hydrochloride
Doxorubicin IV on days 1, 15, and 29.
Drug: tamoxifen citrate
Patients with positive estrogen or progesterone receptors receive oral tamoxifen daily for 5 years.
Procedure: autologous bone marrow transplantation
Stratum III:may receive high dose chemotherapy with stem cell support
Procedure: surgical procedure
Fourteen to 21 days following preoperative chemotherapy, patients undergo a radical, modified radical, or breast sparing surgery plus axillary lymph node dissection.
Radiation: radiation therapy
Radiotherapy is administered 5 days a week for 5.5 weeks.

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 eligible.
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003953

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
Metro Health Medical Center
Cleveland, Ohio, United States, 44109
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Study Chair: Brenda W. Cooper, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00003953     History of Changes
Other Study ID Numbers: CWRU2198, P30CA043703, CWRU-2198, NCI-G99-1537
Study First Received: November 1, 1999
Last Updated: January 25, 2013
Health Authority: United States: Federal Government

Keywords provided by Case Comprehensive Cancer Center:
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Docetaxel
Doxorubicin
Fluorouracil
Liposomal doxorubicin
Methotrexate
Tamoxifen
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Bone Density Conservation Agents
Dermatologic Agents
Enzyme Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators
Folic Acid Antagonists
Hormone Antagonists

ClinicalTrials.gov processed this record on October 30, 2014