An Out Patient Dose Escalation Trial of High Dose Mitoxantrone, Thiotepa and Cyclophosphamide Plus Autologous Blood Cell Rescue and Amifostine Cytoprotection
16 Years
70 Years
Both
Breast Cancer, Drug/Agent Toxicity by Tissue/Organ
Trial Information
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Charles W. Taylor, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Arizona
Authority:
United States: Federal Government
Study ID:
CDR0000065742
NCT ID:
NCT00003068
Start Date:
June 1997
Completion Date:
November 2002
Related Keywords:
- Breast Cancer
- Drug/Agent Toxicity by Tissue/Organ
- stage IV breast cancer
- stage IIIA breast cancer
- recurrent breast cancer
- stage IIIB breast cancer
- drug/agent toxicity by tissue/organ
- Breast Neoplasms
Name | Location |
|---|---|
| Arizona Cancer Center | Tucson, Arizona 85724 |
