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

NCT ID: NCT00002837

Last Updated: 2012-07-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

1995-09-30

Study Completion Date

2002-01-31

Brief Summary

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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

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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.

Conditions

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Breast Cancer

Keywords

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stage IV breast cancer recurrent breast cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Doxorubicin, Paclitaxel + Cyclophosphamide with PBPC

Group Type EXPERIMENTAL

Filgrastim (G-CSF)

Intervention Type BIOLOGICAL

Cyclophosphamide

Intervention Type DRUG

Doxorubicin Hydrochloride

Intervention Type DRUG

Paclitaxel

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Interventions

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Filgrastim (G-CSF)

Intervention Type BIOLOGICAL

Cyclophosphamide

Intervention Type DRUG

Doxorubicin Hydrochloride

Intervention Type DRUG

Paclitaxel

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Other Intervention Names

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Neupogen Cytoxan Neosar Adriamycin PFS Adriamycin RDF Taxol PBSCT Stem Cell Transplant SCT

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically confirmed breast cancer that is metastatic or recurrent Poor-prognosis status required for Phase I portion of the study, i.e.: Estrogen receptor and progesterone receptor-negative tumor OR Failed hormonal therapy and with bulky disease or liver metastasis Bone marrow involvement less than 15% No active CNS metastases

PATIENT CHARACTERISTICS: Age: 15 to 60 Sex: Not specified Performance status: Zubrod 0 or 1 Hematopoietic: WBC greater than 3,500/mm3 Absolute granulocyte count greater than 2,000/mm3 Platelet count greater than 100,000/mm3 Hepatic: Liver function tests less than twice normal Renal: Creatinine clearance (calculated) at least 60 mL/min Cardiovascular: Left ventricular ejection fraction greater than 50% No symptomatic cardiac disease requiring antiarrhythmic or inotropic therapy Pulmonary: DLCO greater than 50% of predicted Other: No pre-existing peripheral neuropathy greater than grade 1 No severe concomitant medical or psychiatric disease

PRIOR CONCURRENT THERAPY: Biologic therapy: More than 3 weeks since any immunotherapy Chemotherapy: No prior doxorubicin or paclitaxel Patients with up to 150 mg per square meter doxorubicin or up to 4 courses of paclitaxel and who have responding disease are eligible for dose-intensive portion of protocol therapy Endocrine therapy: Not specified Radiotherapy: More than 3 weeks since any radiotherapy Surgery: Not specified
Minimum Eligible Age

15 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Bristol-Myers Squibb

INDUSTRY

Sponsor Role collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michele L. Donato, MD

Role: STUDY_CHAIR

M.D. Anderson Cancer Center

Locations

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University of Texas - MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Countries

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United States

Related Links

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http://www.mdanderson.org

UT MD Anderson Cancer Center website

Other Identifiers

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P30CA016672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MDA-DM-95156

Identifier Type: OTHER

Identifier Source: secondary_id

NCI-V96-1017

Identifier Type: -

Identifier Source: secondary_id

CDR0000065052

Identifier Type: REGISTRY

Identifier Source: secondary_id

DM95-156

Identifier Type: -

Identifier Source: org_study_id