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Adjuvant Stage 2-3A Breast Cancer With Positive Lymph Nodes

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00007904
First received: January 6, 2001
Last updated: September 28, 2012
Last verified: September 2012
History of Changes
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim 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. Radiation therapy uses high-energy x-rays to damage tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with filgrastim and radiation therapy works in treating patients with stage II or stage IIIA breast cancer.


Condition Intervention Phase
Breast Cancer
 Biological: filgrastim
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: paclitaxel
Drug: tamoxifen citrate
Procedure: adjuvant therapy
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 Safety And Tolerability Of Adjuvant Chemotherapy With Continuous Infusion Paclitaxel And Dose Intense Cyclophosphamide And Hematopoietic Growth Factor Support Followed By Doxorubicin For Stage II-IIIA Breast Cancer Involving Greater Than or Equal to 10 Lymph Nodes

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • To determine the safety of administering continuous infusion paclitaxel with dose intense cyclophosphamide [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]
    Paclitaxel 160 mg/m2 given over 72 hours by continuous infusion days 1-3 given concurrently with cyclophosphamide 700 mg/m2 daily for 3 day every 3 weeks cycles 1-3. Patients will be observed in the outpatient treatment area during the first 2 hours of the paclitaxel infusion for allergic reactions. Epinephrine, hydrocortisone, and IV antihistamine will be available.

  • To determine the incidence of febrile neutropenia with the first cycle of therapy. [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]
    A specific objective of this trial is to estimate the incidence of febrile neutropenia. The observed incidence of febrile neutropenia with the first cycle of cyclophosphamide and paclitaxel, as well as the observed number of days of grade ¾ neutropenia during the first treatment cycle, will be reported along with 95% confidence intervals.


Secondary Outcome Measures:
  • To determine days of neutrophil counts below 500/uL on this regimen during the first treatment cycle. [ Time Frame: after 1st cycle (3 weeks) ] [ Designated as safety issue: No ]
  • To evaluate dose delays and dose reductions of this regimen. [ Time Frame: at 7 cycles (21 weeks) ] [ Designated as safety issue: No ]
  • To determine disease-free and overall survival of this regimen. [ Time Frame: 5 yrs after treatment ] [ Designated as safety issue: No ]
  • Quality of life as assessed by Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire [ Time Frame: 6 months after treatment ] [ Designated as safety issue: No ]
    Quality of life will be assessed using the FACT-B instrument. Quality of life will be assessed at the following timepoints: Cycle 1 day 1, Cycle 1 day 4, Cycle 2 day 1, on the final day of adriamycin, and 6 months after treatment is completed.

  • Correlation of Her2/neu overexpression with disease-free and overall survival [ Time Frame: 5 yrs after treatment ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: July 2000
Study Completion Date: September 2012
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A: Combination Chemotherapy
Paclitaxel IV continuously over 72 hours on days 1-3 and cyclophosphamide IV on days 1-3. Filgrastim subcutaneously (SC) beginning on day 5 and continuing until blood counts recover or pegfilgrastim SC on day 5. Treatment repeats every 21 days for 3 courses. Then doxorubicin hydrochloride IV on day 1 and filgrastim SC beginning on day 2 and continuing until blood counts recover or pegfilgrastim SC on day 2. Treatment repeats every 21 days for 4 courses. Patients with hormone-receptor positive tumors receive oral tamoxifen citrate or oral anastrozole daily for 5 years following chemotherapy. Beginning 3-6 weeks after completion of chemotherapy, patients undergo radiation therapy 5 days a week for 6-7 weeks.
 Biological: filgrastim
Neupogen (G-CSF) given at a dose of 10 ugm/kg subcutaneously starting on day 5 and continuing until ANC > 10,000/uL x1 day after the nadir cycles 1-3.
Other Names:
  • G-CSF, Neupogen®
  • recominant-methionyl human granulocyte-colony stimulating factor
  • granulocyte colony stimulating factor
  • r-methHuG-CSF
Drug: cyclophosphamide
cyclophosphamide 700 mg/m2 daily for 3 day every 3 weeks cycles 1-3
Other Names:
  • Cytoxan®
  • CTX
  • CPM
  • Neosar®
Drug: doxorubicin hydrochloride
Patients then receive doxorubicin IV on day 1.
Drug: paclitaxel
Paclitaxel 160 mg/m2 given over 72 hours by continuous infusion days 1-3
Other Name: Taxol®
Drug: tamoxifen citrate
tamoxifen at a dose of 20 mg daily for 5 years after chemotherapy is completed
Procedure: adjuvant therapy
Patients receive paclitaxel IV continuously and cyclophosphamide IV over 2 hours on days 1-3. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until day 14 or until blood counts recover. Treatment repeats every 21 days for 3 courses. Patients then receive doxorubicin IV on day 1 and G-CSF SC on days 2-11 every 21 days for 4 courses.
Radiation: radiation therapy
Beginning 3-6 weeks after the completion of chemotherapy, patients receive radiotherapy 5 days a week for 6-7 weeks.

Detailed Description:

OBJECTIVES:

  • Determine the feasibility of administering adjuvant paclitaxel, dose-intensive cyclophosphamide, and filgrastim (G-CSF), followed by doxorubicin and then radiotherapy in patients with stage II or IIIA breast cancer involving > 4 lymph nodes.
  • Determine the incidence of febrile neutropenia in these patients during the first course of therapy.
  • Compare the incidence of febrile neutropenia and duration of neutropenia in patients treated with this regimen with that seen in patients treated on protocol CWRU-4194.
  • Determine the disease-free and overall survival of patients treated with this regimen.
  • Evaluate the quality of life of these patients.
  • Correlate HER-2/neu overexpression with disease-free and overall survival in these patients.

OUTLINE: Patients receive paclitaxel IV continuously and cyclophosphamide IV over 2 hours on days 1-3. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until day 14 or until blood counts recover. Treatment repeats every 21 days for 3 courses. Patients then receive doxorubicin IV on day 1 and G-CSF SC on days 2-11 every 21 days for 4 courses.

Patients with hormone receptor positive disease also receive oral tamoxifen daily for 5 years beginning at the completion of chemotherapy.

Beginning 3-6 weeks after the completion of chemotherapy, patients receive radiotherapy 5 days a week for 6-7 weeks.

Quality of life is assessed days 1 and 4 of the first course of chemotherapy, day 1 of the second course, the last day of the final course, and at 6 months after the completion of treatment.

Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 26 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed stage II or IIIA breast cancer

    • At least 5 axillary lymph nodes
    • No T4 or N3 disease
  • No distant metastases by CT scan of the chest, abdomen, and pelvis; bone scan; and bone marrow evaluation

  • No more than 8 weeks since prior lumpectomy or mastectomy with axillary node dissection

    • Negative surgical margins

  • Hormone receptor status:

    • Hormone receptor status known

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Sex:

  • Male or female

Menopausal status:

  • Not specified

Performance status:

  • ECOG 0-1

Life expectancy:

  • Not specified

Hematopoietic:

  • WBC at least 3,500/mm^3
  • Granulocyte count at least 1,500/mm^3
  • Platelet count greater than 100,000/mm^3

Hepatic:

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • SGOT no greater than 1.5 times ULN
  • Alkaline phosphatase no greater than 1.5 times ULN

Renal:

  • Creatinine no greater than 1.5 mg/dL

Cardiovascular:

  • No poorly controlled ischemic heart disease or congestive heart failure

Pulmonary:

  • No severe chronic obstructive or restrictive pulmonary disease

Other:

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No severe diabetes mellitus
  • No other severe concurrent medical or psychiatric illness that would preclude study participation
  • No other malignancy within past 5 years except curatively treated ductal carcinoma in situ, lobular carcinoma in situ, or breast cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • No prior radiotherapy

Surgery:

  • See Disease Characteristics
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00007904

Locations
United States, Ohio
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-5065
UH-LUICC
Mentor, Ohio, United States, 44060
UH-Chagrin Highlands
Orange Village, Ohio, United States, 44122
Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Study Chair: Brenda W. Cooper, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00007904     History of Changes
Other Study ID Numbers: CWRU1100, P30CA043703, 05-00-23, NCI-G00-1877, CWRU1100, NCI-2010-01068
Study First Received: January 6, 2001
Last Updated: September 28, 2012
Health Authority: United States: Federal Government

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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Adjuvants, Immunologic
Lenograstim
Cyclophosphamide
Doxorubicin
Tamoxifen
Paclitaxel
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
 Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Estrogen Antagonists

ClinicalTrials.gov processed this record on May 19, 2013