Combination Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Stage II or Stage IIIA 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: NCT00003972
Recruitment Status : Completed
First Posted : May 3, 2004
Last Update Posted : April 2, 2010
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center

Brief 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. It is not yet known which regimen of combination chemotherapy is more effective for breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of combination chemotherapy followed by peripheral stem cell transplantation in treating patients who have stage II or stage IIIA breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Biological: filgrastim Biological: sargramostim Drug: busulfan Drug: carboplatin Drug: cyclophosphamide Drug: melphalan Drug: paclitaxel Drug: tamoxifen citrate Drug: thiotepa Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy Phase 3

Detailed Description:

OBJECTIVES: I. Compare early mortality, survival, and disease free survival in patients with node positive stage II or IIIA breast cancer treated with busulfan, melphalan, and thiotepa versus cyclophosphamide, thiotepa, and carboplatin followed by autologous peripheral blood stem cell transplantation. II. Compare the toxicity of these 2 regimens in this patient population.

OUTLINE: This is a randomized study. Patients are stratified according to stage of disease (stage II vs stage IIIA), lymph node status (at least 10 positive nodes vs less than 10 positive nodes), and hormone receptor status (estrogen receptor positive or progesterone receptor positive vs estrogen receptor negative or progesterone receptor negative). All patients initially receive mobilization chemotherapy with cyclophosphamide IV over 1-2 hours on day 1 and paclitaxel IV over 4 hours on day 2. Beginning on day 4, patients receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously each day until the final day of leukapheresis. When blood counts recover, peripheral blood stem cells (PBSC) are harvested. Patients are randomized to 1 of 2 high dose chemotherapy regimens 28-45 days after the last dose of mobilization chemotherapy. Arm I: Patients receive oral busulfan every 6 hours on days -8 to -6, melphalan IV over 30-60 minutes on days -5 and -4, and thiotepa IV over 2 hours on days -3 and -2. PBSC are reinfused on day 0. Arm II: Patients receive cyclophosphamide, thiotepa, and carboplatin by continuous IV infusion over 24 hours on days -7, to -4. PBSC are reinfused on day 0. Beginning 4-6 weeks after the last dose of chemotherapy, patients in both arms receive local radiotherapy 5 days each week for 5 weeks. Patients also receive oral tamoxifen (or equivalent antiestrogen therapy) daily for 5 years if they are estrogen or progesterone receptor positive, postmenopausal, or age 50 and over and perimenopausal. Patients are followed every 3 months for 2 years and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 280 patients (140 per treatment arm) will be accrued for this study over 3 years.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Phase III Study of High-Dose Chemotherapy Using Busulfan, Melphalan and Thiotepa Versus Cyclophosphamide,Thiotepa, Carboplatin Followed by Autologous Stem Cell Transplantation in Patients With High-Risk Primary Stage II or III (Non-Inflammatory) Breast Cancer
Study Start Date : July 1998
Actual Primary Completion Date : March 2003
Actual Study Completion Date : March 2003

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

DISEASE CHARACTERISTICS: Histologically proven stage II breast cancer with 1 of the following: Estrogen receptor negative with at least 4 positive nodes OR Estrogen receptor positive with at least 6 positive nodes OR Histologically proven stage IIIA breast cancer Must have already received 4-7 courses of conventional chemotherapy with a doxorubicin based regimen (which may include paclitaxel or docetaxel) No greater than 60 days since induction chemotherapy Prior definitive surgical treatment of primary lesion (modified radical mastectomy or breast conserving procedure plus axillary node dissection) Margins free of tumor Hormone receptor status: Estrogen and progesterone receptor status known

PATIENT CHARACTERISTICS: Age: 18 to 65 Menopausal status: Not specified Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL SGOT or SGPT no greater than 2 times normal Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular: Left ventricular ejection fraction at least 50% if any of the following: Symptoms of congestive heart failure Abnormal cardiac exam Prior doxorubicin dose greater than 400 mg/m2 Pulmonary: No significant pulmonary disease (DLCO less than 60% predicted) Other: Not pregnant Negative pregnancy test HIV negative No significant active infection No other severe disease that would severely limit life expectancy No other malignancy within past 5 years unless: Chance of survival for greater than 5 years is 90% AND Treated with surgery only (no chemotherapy or radiotherapy)

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics No greater than 1 prior chemotherapy regimen (no greater than 7 prior courses) Endocrine therapy: No concurrent tamoxifen Radiotherapy: Not specified Surgery: See Disease Characteristics Other: No other concurrent experimental agents

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): NCT00003972

United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Study Chair: William I. Bensinger, MD Fred Hutchinson Cancer Research Center Identifier: NCT00003972     History of Changes
Other Study ID Numbers: 1316.00
CDR0000067175 ( Registry Identifier: PDQ )
First Posted: May 3, 2004    Key Record Dates
Last Update Posted: April 2, 2010
Last Verified: March 2010

Keywords provided by Fred Hutchinson Cancer Research Center:
stage II breast cancer
stage IIIA breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents