An Out Patient Dose Escalation Trial of High Dose Mitoxantrone, Thiotepa and Cyclophosphamide Plus Autologous Blood Cell Rescue and Amifostine Cytoprotection
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.
Primary Purpose: Treatment
Charles W. Taylor, MD
University of Arizona
United States: Federal Government
|Arizona Cancer Center||Tucson, Arizona 85724|