High-Dose Chemotherapy and Autologous Blood Cell Transplantation in Treating Patients With Primary, Locally Advanced, or Stage IV Breast Cancer
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Breast Cancer; Drug/Agent Toxicity by Tissue/Organ
Intervention: amifostine trihydrate (Drug); cyclophosphamide (Drug); mitoxantrone hydrochloride (Drug); thiotepa (Drug); peripheral blood stem cell transplantation (Procedure)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: University of Arizona Official(s) and/or principal investigator(s):
Charles W. Taylor, MD, Study Chair, Affiliation: University of Arizona
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 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.
Clinical Details
Official title: An Out Patient Dose Escalation Trial of High Dose Mitoxantrone, Thiotepa and Cyclophosphamide Plus Autologous Blood Cell Rescue and Amifostine Cytoprotection
Study design: Treatment
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.
Eligibility
Minimum age: 16 Years.
Maximum age: 70 Years.
Gender(s): Both.
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
Locations and Contacts
Arizona Cancer Center, Tucson, Arizona 85724, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: June 1997
Last updated: June 17, 2008
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