High-Dose Chemotherapy and Autologous Blood Cell Transplantation in Treating Patients With Primary, Locally Advanced, or Stage IV Breast Cancer
Condition: Breast Cancer; Drug/Agent Toxicity by Tissue/Organ
MeSH terms: Breast Neoplasms; Drug-Related Side Effects and Adverse Reactions
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): amifostine trihydrate; cyclophosphamide; mitoxantrone hydrochloride; thiotepa; peripheral blood stem cell transplantation
Intervention type(s): Drug; Drug; Drug; Drug; Procedure
Intervention MeSH terms: Cyclophosphamide; Thiotepa; Mitoxantrone; Amifostine
Primary purpose: Treatment
Keywords: stage IV breast cancer; stage IIIA breast cancer; recurrent breast cancer; stage IIIB breast cancer; drug/agent toxicity by tissue/organ