Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Women With Breast Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Completed Adult NCI SWOG-S9623 CLB-9640, E-S9623, NCT00002772, S9623

Objectives

I. Compare disease free survival and overall survival in women with operable 
breast cancer and at least 4 positive axillary lymph nodes treated with 
intensive sequential chemotherapy with doxorubicin, paclitaxel, and 
cyclophosphamide versus standard dose doxorubicin and cyclophosphamide 
followed by high dose STAMP I (cyclophosphamide, cisplatin, and carmustine) or 
STAMP V (cyclophosphamide, carboplatin, and thiotepa) and autologous stem cell 
rescue.

II. Compare the toxic effects of these regimens in this patient population.

III. Measure the breast cancer cell content of the peripheral blood progenitor 
cell (PBPC) fractions from patients randomized to the PBPC supported arm and 
correlate the results with the disease free survival, survival, and pattern of 
relapse in these patients.  

Entry Criteria

Disease Characteristics:

Histologically proven adenocarcinoma of the breast with at least 4 involved
axillary and/or intramammary lymph nodes

No known T4, N3, or M1 disease

Dermal lymphatic involvement without clinical inflammatory changes (edema,
peau d'orange, erythema) allowed

Must have undergone breast conserving surgery or modified radical mastectomy
plus axillary lymph node dissection
 Surgical margins negative for invasive or noninvasive ductal carcinoma
 At least 10 nodes sampled
 No more than 12 weeks since definitive surgery

Synchronous bilateral breast carcinoma allowed if:
 Diagnosed within 4 weeks of initial histologic diagnosis
 One breast meets the eligibility criteria
 Other breast has fewer than 10 involved nodes and is not N3 or T4
 Both breasts treated by modified radical mastectomy or breast conserving
  surgery with axillary node dissection

Concurrent registration on S9719

Hormone receptor status:
 Not specified

Prior/Concurrent Therapy:

Biologic therapy:
 Not specified

Chemotherapy:
 No prior chemotherapy

Endocrine therapy:
 No prior hormonal therapy for breast cancer

Radiotherapy:
 No prior radiotherapy to the breast

Surgery:
 See Disease Characteristics

Patient Characteristics:

Age:
 Adult

Sex:
 Female

Menopausal status:
 Any status

Performance status:
 SWOG 0 or 1

Hematopoietic:
 WBC at least 3,000/mm3
 Absolute neutrophil count at least 1,000/mm3
 Platelet count at least 100,000/mm3

Hepatic:
 Bilirubin no greater than 1.5 times upper limit of normal (ULN)
 SGOT no greater than 1.5 times ULN
 Hepatitis C status required 

Renal:
 Creatinine clearance at least 60 mL/min

Cardiovascular:
 Left ventricular ejection fraction at rest at least 45% by MUGA
 No EKG abnormalities unless cleared by a cardiologist
 No uncontrolled or significant cardiac disease
 No congestive heart failure
 No second or third degree heart block or other serious cardiac conduction
  abnormality
 No atrial or ventricular arrhythmia
 No requirement for medication known to affect cardiac conduction unless:
  Given for reasons other than heart failure or arrhythmia
  Cleared by a cardiologist

Pulmonary:
 FVC and FEV1 at least 60% predicted
 DLCO at least 60% predicted

Other:
 HIV negative
 Hepatitis B surface antigen status required
 No serious medical or psychiatric illness that would preclude informed
  consent or study participation
 No second malignancy within the past 5 years except adequately treated 
  basal cell or squamous cell skin cancer, carcinoma in situ of the cervix,
  or intraductal or lobular carcinoma of the breast (diagnosed at any time)
 Not pregnant or nursing 
 Fertile patients must use effective contraception

Expected Enrollment

A total of 1,000 patients (500 per arm) will be accrued for this study within 
5 years.

Outline

This is a randomized, multicenter study.  Patients are stratified by center, 
primary treatment (mastectomy alone vs mastectomy plus radiotherapy following 
chemotherapy vs breast conserving surgery plus radiotherapy following 
chemotherapy), menopausal status (premenopausal vs postmenopausal), estrogen 
and/or progesterone receptor status (positive vs negative vs unknown), N2 
disease (yes vs no), T3 disease (yes vs no), myeloablative chemotherapy 
regimen (STAMP I vs STAMP V), and source of progenitor cells (marrow vs 
peripheral blood vs both).

Patients are randomized to 1 of 2 treatment arms:

Arm I: Patients receive doxorubicin IV over 1 hour on days 1, 15, and 29, 
paclitaxel IV over 24 hours on days 43, 57, and 71, and cyclophosphamide IV 
over 1 hour on days 85, 99, and 113.  Patients receive filgrastim (G-CSF) 
subcutaneously on days 3-10, 17-24, 31-38, 45-52, 59-66, 73-80, 87-94, 
101-108, and 115-122.

Arm II: 
 Mobilization chemotherapy: Patients receive doxorubicin IV over 1 hour and 
 cyclophosphamide IV over 1 hour on days 1, 22, 43, and 64.    
 
 Harvest: Patients undergo harvest of autologous bone marrow and/or 
 peripheral blood stem cells (PBSC).  Patients who undergo harvest of
 PBSC alone do not receive mobilization chemotherapy but receive hematopoietic
 growth factors prior to harvest.  
   
 High dose myeloablative chemotherapy: Patients receive STAMP I OR STAMP V:
  STAMP I: Patients receive cyclophosphamide IV over 1 hour and cisplatin
   IV over 24 hours on days -6 to -4 and carmustine IV over 2 hour on day
    -3.
  STAMP V: Patients receive cyclophosphamide IV over 24 hours, carboplatin
   IV over 24 hours, and thiotepa IV over 24 hours on days -7 to -4.

 Transplantation: Autologous bone marrow and/or PBSC are reinfused on day 0. 

Both arms: Patients who are postmenopausal or who have hormone receptor 
positive disease receive oral tamoxifen daily beginning 4 weeks after the 
completion of chemotherapy and continuing for 5 years.  Patients who underwent 
breast conserving surgery receive locoregional radiotherapy 5 days a week for 
4.5-5.5 weeks beginning 4-6 weeks after the completion of chemotherapy.     
Patients who underwent modified radical mastectomy may receive locoregional 
radiotherapy 5 days a week for 5 weeks at the discretion of their physician. 

Patients are followed every 4 months for 3 years, every 6 months for 2 years, 
and then annually thereafter.

Moore HC, Green SJ, Gralow JR, et al.: Intensive dose-dense compared with high-dose adjuvant chemotherapy for high-risk operable breast cancer: Southwest Oncology Group/Intergroup study 9623. J Clin Oncol 25 (13): 1677-82, 2007.[PUBMED Abstract]

Bearman SI, Green S, Gralow J, et al.: SWOG/Intergroup 9623: a phase III comparison of intensive sequential chemotherapy to high dose chemotherapy and autologous hematopoietic progenitor cell support (AHPCS) for primary breast cancer in women with =4 involved axillary lymph nodes. [Abstract] J Clin Oncol 23 (Suppl 16): A-572, 21s, 2005.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Scott Bearman, MD, Protocol chair(Contact information may not be current)		Ph: 303-372-9000; 800-473-2288

Eastern Cooperative Oncology Group

Antonio Wolff, MD, Protocol chair		Ph: 410-614-4192 Email: awolff@jhmi.edu

Cancer and Leukemia Group B

Clifford Hudis, MD, Protocol chair		Ph: 646-888-4551; 800-525-2225

Registry Information
Official Title		A COMPARISON OF INTENSIVE SEQUENTIAL CHEMOTHERAPY USING DOXORUBICIN PLUS PACLITAXEL PLUS CYCLOPHOSPHAMIDE WITH HIGH DOSE CHEMOTHERAPY AND AUTOLOGOUS HEMATOPOIETIC PROGENITOR CELL SUPPORT FOR PRIMARY BREAST CANCER IN WOMEN WITH 4-9 INVOLVED AXILLARY LYMPH NODES
Trial Start Date		1996-07-01
Registered in ClinicalTrials.gov		NCT00002772
Date Submitted to PDQ		1996-07-01
Information Last Verified		2007-05-08
NCI Grant/Contract Number		CA32102