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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00007904
• Other study ID #: CWRU1100
• Secondary ID: P30CA04370305-00
• Status: Completed
• Phase: Phase 2
• First received: January 6, 2001
• Last updated: September 28, 2012
• Start date: July 2000
• Est. completion date: September 2012

Study information

• Verified date: September 2012
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 2012
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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.

Drug:
• cyclophosphamide
cyclophosphamide 700 mg/m2 daily for 3 day every 3 weeks cycles 1-3
• doxorubicin hydrochloride
Patients then receive doxorubicin IV on day 1.
• paclitaxel
Paclitaxel 160 mg/m2 given over 72 hours by continuous infusion days 1-3
• 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.

Locations

Country	Name	City	State
United States	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

Sponsors (2)

Lead Sponsor	Collaborator
Case Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the safety of administering continuous infusion paclitaxel with dose intense cyclophosphamide	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.	9 weeks	Yes
Primary	To determine the incidence of febrile neutropenia with the first cycle of therapy.	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.	3 weeks	Yes
Secondary	To determine days of neutrophil counts below 500/uL on this regimen during the first treatment cycle.		after 1st cycle (3 weeks)	No
Secondary	To evaluate dose delays and dose reductions of this regimen.		at 7 cycles (21 weeks)	No
Secondary	To determine disease-free and overall survival of this regimen.		5 yrs after treatment	No
Secondary	Quality of life as assessed by Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire	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.	6 months after treatment	No
Secondary	Correlation of Her2/neu overexpression with disease-free and overall survival		5 yrs after treatment	No

External Links

•   Clinical trial summary from the National Cancer Institute's PDQ® database