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High-Dose Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Breast Cancer

Phase 1
Completed
Conditions
Breast Cancer
Interventions
Biological: Filgrastim (G-CSF)
Procedure: Peripheral Blood Stem Cell Transplantation
Registration Number
NCT00002837
Lead Sponsor
M.D. Anderson Cancer Center
Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining peripheral stem cell transplantation with chemotherapy may kill more tumor cells.

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

Detailed Description

OBJECTIVES: I. Define the maximum tolerated doses of four courses of doxorubicin (DOX), paclitaxel (TAX), and cyclophosphamide (CTX) followed by peripheral blood stem cell (PBSC) and granulocyte colony-stimulating factor support given in an out-patient setting in patients with metastatic breast cancer. II. Evaluate the cardiotoxicity of the combination of bolus DOX, a 3-hour infusion of TAX, and CTX. III. Determine the clinical response rate and time to progression associated with this regimen. IV. Determine Cmax, AUC and the drug:metabolite ratio of TAX and DOX when given with CTX, a known p450 inducer.

OUTLINE: Patients without prior doxorubicin (DOX) or paclitaxel (TAX) receive two courses of induction chemotherapy with DOX/TAX with G-CSF support given 3 weeks apart. Peripheral blood stem cells (PBSC) are harvested during the recovery phase following the second course. Patients who previous received DOX or TAX and responded receive cyclophosphamide (CTX) with G-CSF for stem cell mobilization followed by PBSC harvest. Back-up bone marrow may be harvested from patients without marrow involvement for whom PBSC collection is inadequate. Patients with responding or stable disease who have adequate PBSC available receive dose-intensive chemotherapy with DOX, CTX, and TAX given on day 1, with PBSC infused on day 3 and G-CSF given from day 3 until neutrophil recovery. Four courses of dose-intensive chemotherapy with PBSC and G-CSF support are given every 3-4 weeks. During the phase I portion of the study, groups of 3-6 patients are treated at increasing doses of DOX, TAX, and CTX until the maximum tolerated dose (MTD) is determined; during the phase II portion, additional patients are treated at the MTD. Patients who progress after 2 courses of induction or 2 courses of dose-intensive chemotherapy are given the option of receiving their PBSC after conditioning with a different regimen (e.g., CTX, etoposide, and cisplatin). Patients who receive induction on protocol but who choose not to receive dose-intensive chemotherapy continue DOX/TAX for a total of 6 courses. Patients are followed 3, 6, 12, 18, and 24 months after therapy, then as clinically indicated.

PROJECTED ACCRUAL: During the phase I portion of the study, groups of 3-6 patients will be entered at each dose level studied. During the phase II portion of the study, 25 patients will be treated at the maximum tolerated dose.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
21
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Doxorubicin, Paclitaxel + Cyclophosphamide with PBPCFilgrastim (G-CSF)-
Doxorubicin, Paclitaxel + Cyclophosphamide with PBPCPeripheral Blood Stem Cell Transplantation-
Doxorubicin, Paclitaxel + Cyclophosphamide with PBPCDoxorubicin Hydrochloride-
Doxorubicin, Paclitaxel + Cyclophosphamide with PBPCCyclophosphamide-
Doxorubicin, Paclitaxel + Cyclophosphamide with PBPCPaclitaxel-
Primary Outcome Measures
NameTimeMethod
Maximum Tolerated Doses (MTD) of 4 courses Doxorubicin, Paclitaxel, + Cyclophosphamide followed by PBSC and G-CSF SupportEvaluated with each 3-4 week course
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

University of Texas - MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

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