High-Dose Chemotherapy and Autologous Blood Cell Transplantation in Treating Patients With Primary, Locally Advanced, or Stage IV Breast Cancer

An Out Patient Dose Escalation Trial of High Dose Mitoxantrone, Thiotepa and Cyclophosphamide Plus Autologous Blood Cell Rescue and Amifostine Cytoprotection

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 and kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of high-dose mitoxantrone, thiotepa, and cyclophosphamide plus autologous peripheral stem cell transplantation and amifostine in treating patients with primary, locally advanced, or stage IV breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Drug/Agent Toxicity by Tissue/Organ
• Intervention / Treatment: Drug: cyclophosphamide; Drug: mitoxantrone hydrochloride; Drug: amifostine trihydrate; Drug: thiotepa; Procedure: peripheral blood stem cell transplantation

Detailed Description

OBJECTIVES: I. Determine the maximum tolerated doses of mitoxantrone and cyclophosphamide when administered in combination with thiotepa, autologous blood cells, and amifostine in patients with primary, locally advanced, or metastatic breast cancer, and determine whether amifostine, a cytoprotection agent, allows administration of high dose chemotherapy. II. Determine the dose limiting toxicities of this regimen when administered to patients with primary, locally advanced, or metastatic breast cancer. III. Evaluate the toxicities of amifostine, a cytoprotection agent, when administered in multiple doses to breast cancer patients receiving high dose chemotherapy and autologous blood cell transplantation. IV. Document the antitumor efficacy of this regimen versus freedom from recurrence and overall survival after autologous blood cell transplantation. V. Assess the contribution of disease, treatment, and personal characteristics affecting the quality of life in these patients and the patient's primary caregiver.

OUTLINE: This is a dose escalation study. Autologous blood cells are collected after completion of neoadjuvant/induction chemotherapy (and salvage mastectomy, if indicated). Patients receive IV amifostine, mitoxantrone, and thiotepa on day -7. On day -6, patients receive IV amifostine, thiotepa, and cyclophosphamide treatment. On days -5, -4, and -3, IV amifostine and cyclophosphamide are administered to participants. Following high dose chemotherapy treatment, patients rest on days -2 and -1. On day 0, patients undergo autologous blood cell transplantation. Cohorts of 3 patients each receive escalating doses of mitoxantrone and cyclophosphamide. If 1 of 3 patients at a given dose level experiences dose limiting toxicity (DLT), an additional 3 patients are treated at that dose. If at least 3 of 6 patients experience DLT at a given dose level, then the maximum tolerated dose is the previous dose level. Patients are followed at day 100, then every 6 months for 2 years, then annually until death.

PROJECTED ACCRUAL: A total of 30 patients will be accrued.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Arizona Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 70 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS: Histologically proven primary, locally advanced (at least 10 axillary lymph node metastases or T4 or N2, M0 disease), or stage IV breast cancer Patients with at least 10 axillary node metastases and no distant metastases receive adjuvant chemotherapy with a doxorubicin containing regimen Patients with T4 or N2, M0 disease and no prior chemotherapy receive neoadjuvant or induction chemotherapy prior to salvage mastectomy (patients must show partial remission based on tumor palpation) Patients with stage IV breast cancer receive induction chemotherapy with doxorubicin (unless relapsed less than 1 year following therapy or metastatic disease progression observed or greater than 300 mg/m2 previously taken, then may receive induction chemotherapy with paclitaxel regimen) Stage IV cancer patients must have at least a partial remission following induction chemotherapy Stage IV cancer patients should have minimal metastatic disease (chest wall recurrence or bone only); patients with more extensive and/or visceral metastases must have near complete remission following induction chemotherapy

PATIENT CHARACTERISTICS: Age: 16 to 70 Performance Status: SWOG 0-1 Karnofsky 80-100% Life Expectancy: At least 2 months Hematopoietic: Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin less than 2.0 times upper limit of normal (ULN) (unless tumor related) SGOT and SGPT less than 2.0 times ULN (unless tumor related) Alkaline phosphatase less than 2.0 times ULN (unless tumor related) Renal: Creatinine within institutional normal limits Cardiovascular: Cardiac ventricular ejection fraction (MUGA) or echocardiogram within normal limits prior to high dose chemotherapy No uncontrolled or severe cardiovascular disease No myocardial infarction within 6 months No congestive heart failure No symptomatic angina No life threatening arrhythmias No hypertension Pulmonary: Pulmonary function tests greater than 75% predicted normal Room air arterial blood gases within normal limits Other: Not HIV positive Not hepatitis B surface antigen positive Not hepatitis C antibody positive No serious organ dysfunction (unless caused by breast cancer) No active bacterial, viral, or fungal infections No active peptic ulcers No uncontrolled diabetes Not pregnant Effective contraceptive method must be used during study Negative pregnancy test

PRIOR CONCURRENT THERAPY: See Disease Characteristics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT

Collaborators and Investigators

• Sponsor: University of Arizona
• Investigators: Study Chair: Charles W. Taylor, MD, University of Arizona

Study record dates

Study Major Dates

• Study Start: June 1, 1997
• Study Completion (ACTUAL): November 1, 2002

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: July 30, 2004
• First Posted (ESTIMATE): August 2, 2004

Study Record Updates

• Last Update Posted (ESTIMATE): January 31, 2013
• Last Update Submitted That Met QC Criteria: January 30, 2013
• Last Verified: May 1, 2006

More Information

Terms related to this study

• Keywords: stage IV breast cancer; stage IIIA breast cancer; recurrent breast cancer; stage IIIB breast cancer; drug/agent toxicity by tissue/organ
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Radiation-Protective Agents; Cyclophosphamide; Mitoxantrone; Thiotepa; Amifostine
• Other Study ID Numbers: CDR0000065742; UARIZ-HSC-9728; ALZA-UARIZ-HSC-9728; NCI-V97-1329