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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003068
First received: November 1, 1999
Last updated: January 30, 2013
Last verified: May 2006
  Purpose

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 Intervention Phase
Breast Cancer
Drug/Agent Toxicity by Tissue/Organ
Drug: amifostine trihydrate
Drug: cyclophosphamide
Drug: mitoxantrone hydrochloride
Drug: thiotepa
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: An Out Patient Dose Escalation Trial of High Dose Mitoxantrone, Thiotepa and Cyclophosphamide Plus Autologous Blood Cell Rescue and Amifostine Cytoprotection

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment: 30
Study Start Date: June 1997
Study Completion Date: November 2002
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

Ages Eligible for Study:   16 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00003068

Locations
United States, Arizona
Arizona Cancer Center
Tucson, Arizona, United States, 85724
Sponsors and Collaborators
University of Arizona
Investigators
Study Chair: Charles W. Taylor, MD University of Arizona
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00003068     History of Changes
Other Study ID Numbers: CDR0000065742, UARIZ-HSC-9728, ALZA-UARIZ-HSC-9728, NCI-V97-1329
Study First Received: November 1, 1999
Last Updated: January 30, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Thiotepa
Mitoxantrone
Amifostine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Radiation-Protective Agents
Protective Agents
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 20, 2014