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

Phase 2
Completed
Conditions
Breast Cancer
Interventions
Biological: filgrastim
Procedure: adjuvant therapy
Radiation: radiation therapy
Registration Number
NCT00007904
Lead Sponsor
Case Comprehensive Cancer Center
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm A: Combination ChemotherapyfilgrastimPaclitaxel 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.
Arm A: Combination Chemotherapytamoxifen citratePaclitaxel 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.
Arm A: Combination Chemotherapyadjuvant therapyPaclitaxel 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.
Arm A: Combination Chemotherapyradiation therapyPaclitaxel 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.
Arm A: Combination ChemotherapycyclophosphamidePaclitaxel 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.
Arm A: Combination Chemotherapydoxorubicin hydrochloridePaclitaxel 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.
Arm A: Combination ChemotherapypaclitaxelPaclitaxel 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.
Primary Outcome Measures
NameTimeMethod
To determine the safety of administering continuous infusion paclitaxel with dose intense cyclophosphamide9 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
NameTimeMethod
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) questionnaire6 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 survival5 yrs after treatment

Trial Locations

Locations (3)

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

🇺🇸

Cleveland, Ohio, United States

UH-LUICC

🇺🇸

Mentor, Ohio, United States

UH-Chagrin Highlands

🇺🇸

Orange Village, Ohio, United States

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