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. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. It is not yet known which treatment regimen is more effective for breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy plus filgrastim with filgrastim alone in treating women undergoing peripheral stem cell transplantation for stage II, stage III , or metastatic breast cancer.

Condition	Treatment or Intervention	Phase
recurrent breast cancer	Procedure: chemotherapy  Procedure: biological response modifier therapy  Procedure: colony-stimulating factor therapy  Procedure: peripheral blood stem cell transplantation  Procedure: cytokine therapy  Drug: bone marrow ablation with stem cell support  Drug: carmustine  Drug: cisplatin  Drug: cyclophosphamide  Drug: etoposide  Drug: filgrastim  Drug: thiotepa	Phase III

Further Study Details: 

OBJECTIVES: I. Determine whether high dose chemotherapy in addition to growth factors increases the yield of filgrastim mobilized progenitor cells. II. Determine the kinetics of hematopoietic reconstitution following myeloablative therapy and mobilized blood stem cell transplantation. III. Determine whether the use of high dose chemotherapy in addition to growth factors for mobilization of stem cells reduces risk of relapse as measured by time to progression in responsive relapsed breast cancer patients receiving autologous peripheral blood stem cell or bone marrow transplants. IV. Determine the morbidity and cost differences of the use of high dose chemotherapy plus growth factors compared to growth factors alone for mobilization of peripheral blood progenitors and treatment of breast cancer with high dose chemotherapy.

PROTOCOL OUTLINE: Patients will be randomized into 2 groups. Group 1 patients undergo CVP chemotherapy treatment IV on days 1-3, with cyclophosphamide (CTX), etoposide, and cisplatin. Filgrastim SC is given on day 4 every 12 hours until completion of apheresis. Group 2 patients only receive filgrastim SC given on day 1 every 12 hours until completion of apheresis. Stem cells are removed beginning on day 4 for a maximum of 6 days. Upon recovery of hematopoiesis patients then receive high IV doses of CBT chemotherapy with CTX, carmustine, and thiotepa for 3 days, followed 4 days later by autologous stem cell reinfusion. Beginning on day of reinfusion, filgrastim is given bid until WBC reaches a safe level. Patients are followed for 90 days posttransplant, and then followed indefinitely for antitumor response and time to progression.

PROJECTED ACCRUAL: This study will include about 218 patients.

Ages Eligible for Study:  18 Years   -   65 Years

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Female patients with Stage II, III or IV breast carcinoma in remission, and not eligible for protocols of higher priority (DM89-102)
• Stage II breast cancer must have spread to at least 10 axillary nodes; patients with fewer than 10 nodes must have extranodal extensions
• Patients with greater than 75% positive nodes for tumor are eligible
• No bone marrow involvement with tumor by standard histopathological exam of bilateral iliac marrow biopsies 2 weeks prior to study
• Prior normalization of markers needed in patients with elevated tumor markers (e.g., CEA)
• Metastatic disease patients must have documentation verifying at least 50% reduction of all sites of disease, except bone
• Stable bone metastases measured via bone scan are eligible
• Responsive disease but with large tumor burden should enter high risk BMT protocols (93-090)

--Prior/Concurrent Therapy--

• No concurrent involvement in any other clinical trial that effects engraftment
• Biologic therapy: No growth factors within 1 week
• Chemotherapy: No more than 2 chemotherapy regimens allowed after relapse for metastatic disease; Chemotherapy responsive disease prior to study; Stage II/III disease receiving neoadjuvant chemotherapy allowed with at least 4 positive nodes at mastectomy; No partial response to chemotherapy less than 50% of any site except bone; No prior chemotherapy treatment with carmustine
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: Mastectomy allowed

--Patient Characteristics--

• Age: 18 to 65
• Performance status: Zubrod 0-1
• Life expectancy: Not specified
• Hematopoietic: WBC greater than 3,000/mm3; Platelet count greater than 100,000/mm3; No hematopoietic growth factor treatments
• Hepatic: Bilirubin, SGOT, and SGPT less than 2 times normal
• Renal: Estimated creatinine clearance greater
• Cardiovascular: Normal ejection fraction
• Pulmonary: DLCO greater than 50% of predicted
• Other: Not HIV positive; Not pregnant 2 weeks prior to study; No comorbid condition placing patient at high risk for complications; No prior active infections; No history of untreated central nervous system (CNS) disease; No allergic response to eggs or murine protein

Texas
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4009,  United States

Study chairs or principal investigators

James Gajewski,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000065048; MDA-DM-95047; NCI-G96-1014
Record last reviewed:  November 2003
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002836
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08