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

Sponsor

Case Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00007904

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

146

Duration (Months)

5.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: filgrastim Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel Drug: tamoxifen citrate Procedure: adjuvant therapy Radiation: radiation therapy	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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

Study Start Date :

Jul 1, 2000

Actual Primary Completion Date :

Jun 1, 2006

Actual Study Completion Date :

Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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.

Arm

Intervention/Treatment

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 Names:

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.

Outcome Measures

Primary Outcome Measures

To determine the safety of administering continuous infusion paclitaxel with dose intense cyclophosphamide [9 weeks]
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. [3 weeks]
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. [after 1st cycle (3 weeks)]
To evaluate dose delays and dose reductions of this regimen. [at 7 cycles (21 weeks)]
To determine disease-free and overall survival of this regimen. [5 yrs after treatment]
Quality of life as assessed by Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire [6 months after treatment]
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 [5 yrs after treatment]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
2	UH-LUICC	Mentor	Ohio	United States	44060
3	UH-Chagrin Highlands	Orange Village	Ohio	United States	44122