High-Dose Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Recurrent or Refractory Metastatic Breast Cancer

Breast Cancer Clinical Trial

Official title:

Multiple Cycles of High Dose Chemotherapy Supported With Filgrastim and Peripheral Blood Progenitor Cells in Patients With Metastatic Breast Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003392
• Other study ID #: LCCC 9727
• Secondary ID: UNC-LCCC-970135N
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: February 19, 2012
• Start date: September 1997
• Est. completion date: January 2003

Study information

• Verified date: February 2012
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• 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. Combining chemotherapy with peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of high-dose chemotherapy and peripheral stem cell transplantation in treating patients with recurrent or refractory metastatic breast cancer.

Description:

OBJECTIVES: I. Determine the effects on 2 year progression-free survival of a regimen consisting of cyclophosphamide, paclitaxel, and filgrastim (G-CSF) to mobilize peripheral blood progenitor cells (PBPCs), followed by 2 courses of carboplatin and paclitaxel followed by 1 course of melphalan, each supported with PBPCs and G-CSF, in patients with recurrent or refractory, advanced breast cancer. II. Evaluate the feasibility of administering multiple courses of high dose chemotherapy in an outpatient setting for these patients. III. Evaluate the rate of complete response to the high dose therapy in these patients.

OUTLINE: This is a multicenter study. Patients receive mobilization therapy consisting of cyclophosphamide IV over 1 hour followed by paclitaxel IV over 3 hours, then filgrastim (G-CSF) beginning 24 hours following completion of paclitaxel and continuing through the last day of leukapheresis. Leukapheresis continues until an adequate number of CD34+ cells is collected. Following cell count recovery, patients receive 3 courses of high-dose chemotherapy: 2 courses of paclitaxel IV over 3 hours followed by carboplatin IV over 1 hour, with the first course generally within 21 days after completion of leukapheresis and the second course 21-35 days after the first; then 1 course of melphalan IV infused over 30 minutes 21-35 days after the previous carboplatin dose. Each course of chemotherapy is followed 24-48 hours later by the infusion of G-CSF-mobilized peripheral blood progenitor cells and G-CSF. Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 96 evaluable patients will be accrued for this study over 3 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 61
• Est. completion date: January 2003
• Est. primary completion date: August 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

DISEASE CHARACTERISTICS: Histologically proven recurrent or refractory, metastatic breast cancer Patients previously treated for metastatic disease must show response to last standard dose chemotherapy regimen within 60 days of study entry OR Patients with no evidence of disease (e.g., resected skin lesions) must show no evidence of progression or bone disease No CNS metastases No disease progression following prior platinum or paclitaxel based regimens Hormone receptor status: Not specified

PATIENT CHARACTERISTICS: Age: 18 to 65 Sex: Not specified Menopausal status: Not specified Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 90,000/mm3 No prior inability to mobilize adequate peripheral blood progenitor cells for high dose therapy Hepatic: Bilirubin no greater than 1.8 mg/dL Transaminases stable and no greater than 3 times upper limit of normal Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: LVEF within normal limits No significant cardiovascular disease No coronary artery disease No arrhythmias No congestive heart failure Other: Not pregnant or nursing Negative pregnancy test required of fertile women Effective contraception required of fertile patients Not HIV positive No nonmalignant disease precluding protocol treatment No sensitivity to E. coli-derived drug preparations No prior participation in this study No greater than grade I neurotoxicity

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior cellular support for high dose chemotherapy Chemotherapy: See Disease Characteristics No more than 6 prior courses of chemotherapy for metastatic disease At least 3 weeks since prior chemotherapy and recovered No prior high dose chemotherapy with cellular support Endocrine therapy: No concurrent steroid therapy Concurrent hormonal therapy allowed Radiotherapy: At least 3 weeks since prior radiotherapy and recovered No prior extensive pelvic radiation Surgery: Not specified Other: Recovered from acute toxic effects of any prior therapy No concurrent anticoagulation therapy

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• filgrastim
10 mcg/kg/d, day 2 through last day of leukapheresis

Drug:
• carboplatin
18 AUC IV, approximately days 21, 42
• cyclophosphamide
4 gm/m2 IV, day 1
• melphalan
140 mg/m2 IV , approximately day 63
• paclitaxel
170 mg/m2 IV day 1

Procedure:
• bone marrow ablation with stem cell support

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Bone Marrow Stem Cell Transplant Institute of Florida	Fort Lauderdale	Florida
United States	Scripps Clinic	La Jolla	California
United States	University of California San Diego	La Jolla	California
United States	Methodist Hospital-Central Unit	Memphis	Tennessee
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Stem Cell Sciences	New York	New York
United States	Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	Temple University Cancer Center	Philadelphia	Pennsylvania
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	University of Rochester School of Medicine	Rochester	New York
United States	New York Medical College	Valhalla	New York
United States	Walter Reed Army Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,