Filgrastim Plus Chemotherapy Compared With Filgrastim Alone In Treating Women Undergoing Peripheral Stem Cell Transplantation For Breast Cancer

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00002836
First received: November 1, 1999
Last updated: July 27, 2012
Last verified: July 2012
  Purpose

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 Intervention Phase
Breast Cancer
Biological: Filgrastim (G-CSF)
Drug: Carmustine
Drug: Cisplatin
Drug: Cyclophosphamide (CTX)
Drug: Etoposide
Drug: Thiotepa
Procedure: Peripheral Blood Stem Cell Transplantation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Comparison of High Dose Chemotherapy G-CSF To G-CSF For Mobilization of Peripheral Blood Stem Cells For Autologous Transplantation For Patients With Responsive Metastatic Breast Cancer Or High Risk Stage II-III Patients

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Compare Effectiveness of Chemotherapy + Filgrastim to Filgrastim Alone [ Time Frame: 90 Days Post Transplant ] [ Designated as safety issue: No ]

Enrollment: 184
Study Start Date: May 1995
Study Completion Date: March 2006
Primary Completion Date: March 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Filgrastim + Chemotherapy Biological: Filgrastim (G-CSF)
For group one (Filgrastim + Chemotherapy), given under the skin (SC) on day 4 every 12 hours until completion of apheresis; for group two (Filgrastim alone), beginning on day of reinfusion twice a day (bid) until white blood count (WBC) reaches a safe level.
Other Names:
  • Neupogen
  • G-CSF
Drug: Carmustine
Upon recovery of hematopoiesis patients then receive high by vein (IV) doses of CBT chemotherapy with CTX, carmustine, and thiotepa for 3 days
Other Names:
  • BCNU
  • BiCNU
Drug: Cisplatin
As part of CVP chemotherapy treatment by vein (IV) on days 1-3.
Other Names:
  • Platinol-AQ
  • Platinol
  • CDDP
Drug: Cyclophosphamide (CTX)
In group one (Filgrastim + Chemotherapy) as part of CVP chemotherapy treatment by vein (IV) on days 1-3; and group two (Filgrastim alone), upon recovery of hematopoiesis receive high IV doses of CBT chemotherapy with CTX, carmustine, and thiotepa for 3 days.
Other Names:
  • Cytoxan
  • Neosar
Drug: Etoposide
CVP chemotherapy treatment IV on days 1-3, with cyclophosphamide (CTX), etoposide, and cisplatin.
Other Name: VePesid
Drug: Thiotepa
Upon recovery of hematopoiesis receive high IV doses of CBT chemotherapy with CTX, carmustine, and thiotepa for 3 days.
Procedure: Peripheral Blood Stem Cell Transplantation
Infusion of stem cells on Day 0.
Other Names:
  • PBSCT
  • Stem Cell Transplant
Experimental: Filgrastim Biological: Filgrastim (G-CSF)
For group one (Filgrastim + Chemotherapy), given under the skin (SC) on day 4 every 12 hours until completion of apheresis; for group two (Filgrastim alone), beginning on day of reinfusion twice a day (bid) until white blood count (WBC) reaches a safe level.
Other Names:
  • Neupogen
  • G-CSF
Drug: Carmustine
Upon recovery of hematopoiesis patients then receive high by vein (IV) doses of CBT chemotherapy with CTX, carmustine, and thiotepa for 3 days
Other Names:
  • BCNU
  • BiCNU
Drug: Cyclophosphamide (CTX)
In group one (Filgrastim + Chemotherapy) as part of CVP chemotherapy treatment by vein (IV) on days 1-3; and group two (Filgrastim alone), upon recovery of hematopoiesis receive high IV doses of CBT chemotherapy with CTX, carmustine, and thiotepa for 3 days.
Other Names:
  • Cytoxan
  • Neosar
Drug: Thiotepa
Upon recovery of hematopoiesis receive high IV doses of CBT chemotherapy with CTX, carmustine, and thiotepa for 3 days.
Procedure: Peripheral Blood Stem Cell Transplantation
Infusion of stem cells on Day 0.
Other Names:
  • PBSCT
  • Stem Cell Transplant

Detailed Description:

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.

OUTLINE: Patients will be randomized into 2 groups. Group 1 patients undergo CVP chemotherapy treatment by vein (IV) on days 1-3, with cyclophosphamide (CTX), etoposide, and cisplatin. Filgrastim SC (subcutaneously) 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)

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 than 60 mL/min 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

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

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002836

Locations
United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Study Chair: James Gajewski, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00002836     History of Changes
Other Study ID Numbers: DM95-047, P30CA016672, MDA-DM-95047, NCI-G96-1014, CDR0000065048
Study First Received: November 1, 1999
Last Updated: July 27, 2012
Health Authority: United States: Federal Government

Keywords provided by M.D. Anderson Cancer Center:
recurrent breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Carmustine
Cyclophosphamide
Thiotepa
Etoposide phosphate
Cisplatin
Etoposide
Lenograstim
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on April 17, 2014