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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00002837
Recruitment Status : Completed
First Posted : July 1, 2004
Last Update Posted : July 31, 2012
National Cancer Institute (NCI)
Bristol-Myers Squibb
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: Filgrastim (G-CSF) Drug: Cyclophosphamide Drug: Doxorubicin Hydrochloride Drug: Paclitaxel Procedure: Peripheral Blood Stem Cell Transplantation Phase 1 Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I-II Study of Dose Intense Doxorubicin, Paclitaxel And Cyclophosphamide With Peripheral Blood Progenitor Cells (PBPC) And Cytokine Support In Patients With Metastatic Breast Cancer
Study Start Date : September 1995
Actual Primary Completion Date : January 2002
Actual Study Completion Date : January 2002

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Doxorubicin, Paclitaxel + Cyclophosphamide with PBPC Biological: Filgrastim (G-CSF)
Other Name: Neupogen

Drug: Cyclophosphamide
Other Names:
  • Cytoxan
  • Neosar

Drug: Doxorubicin Hydrochloride
Other Names:
  • Adriamycin PFS
  • Adriamycin RDF

Drug: Paclitaxel
Other Name: Taxol

Procedure: Peripheral Blood Stem Cell Transplantation
Other Names:
  • Stem Cell Transplant
  • SCT

Primary Outcome Measures :
  1. Maximum Tolerated Doses (MTD) of 4 courses Doxorubicin, Paclitaxel, + Cyclophosphamide followed by PBSC and G-CSF Support [ Time Frame: Evaluated with each 3-4 week course ]

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Ages Eligible for Study:   15 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00002837

United States, Texas
University of Texas - MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Bristol-Myers Squibb
Study Chair: Michele L. Donato, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00002837     History of Changes
Other Study ID Numbers: DM95-156
P30CA016672 ( U.S. NIH Grant/Contract )
MDA-DM-95156 ( Other Identifier: UT MD Anderson Cancer Center )
CDR0000065052 ( Registry Identifier: NCI PDQ )
First Posted: July 1, 2004    Key Record Dates
Last Update Posted: July 31, 2012
Last Verified: July 2012

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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Liposomal doxorubicin
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors