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.

Condition	Treatment or Intervention	Phase
stage IIIB breast cancer Drug Toxicity stage IIIA breast cancer stage IV breast cancer recurrent breast cancer	Drug: amifostine  Drug: cyclophosphamide  Drug: mitoxantrone  Drug: thiotepa	Phase II

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  16 Years   -   70 Years

Criteria

PROTOCOL ENTRY 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

--Prior/Concurrent Therapy--

• See Disease Characteristics

--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

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

Study chairs or principal investigators

Charles W. Taylor,  Study Chair,  Arizona Cancer Center   

Study ID Numbers:  CDR0000065742; UARIZ-HSC-9728; NCI-V97-1329; ALZA-UARIZ-HSC-9728
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003068
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08