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High Dose Paclitaxel Added to Cyclophosphamide and Thiotepa Followed by Autologous Stem Cell Rescue: A Phase I Trial in Advanced Breast Cancer

Phase 1
60 Years
Not Enrolling
Breast Cancer

Thank you

Trial Information

High Dose Paclitaxel Added to Cyclophosphamide and Thiotepa Followed by Autologous Stem Cell Rescue: A Phase I Trial in Advanced Breast Cancer

OBJECTIVES: I. Determine the maximum tolerated dose of paclitaxel when combined with high
dose cyclophosphamide and thiotepa followed by autologous peripheral blood stem cell
transplantation and radiotherapy in patients with advanced breast cancer. II. Assess the
overall safety and toxicity of this regimen in these patients.

OUTLINE: This is a dose escalation study of paclitaxel. Mobilization and harvest: Patients
undergo mobilization of peripheral blood stem cells (PBSC) according to the protocol
currently used or patients may be mobilized using cytokines alone or chemomobilization at
the discretion of the attending physician. PBSC are harvested and selected for CD34+ cells.
If an adequate number of CD34+ cells are not harvested, autologous bone marrow may be used.
Preparative regimen: Patients receive paclitaxel IV over 24 hours on day -5 and high dose
thiotepa IV over 2 hours and high dose cyclophosphamide IV over 2 hours on day -6, day -4
following paclitaxel infusion, and day -2. Cohorts of 3-6 patients receive escalating doses
of paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as
the dose preceding that at which 2 of 3 or 3 of 6 patients experience dose limiting
toxicity. Transplantation: PBSC are reinfused on day 0 or a minimum of 48 hours after
completion of chemotherapy. Patients receive filgrastim (G-CSF) subcutaneously beginning on
day 0 and continuing until 3 days after blood counts have recovered. Sites of
pretransplantation metastases greater than 3 cm are irradiated beginning after PBSC
transplantation and after blood counts recover. Patients are followed every month for 1
year, then every 3 months thereafter.

PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study within 1 year.

Inclusion Criteria

DISEASE CHARACTERISTICS: Histologically proven stage III or IV breast cancer Must have
responding disease (at least 50% reduction in the sum of the products of all diameters of
measurable nonbony lesions and at least symptomatic improvement in painful bone disease)
following conventional dose chemotherapy Asymptomatic patients with bony disease eligible
if no new lesions or other evidence of bone progression If only bone disease present,
there must be no new bony lesions following cytoreductive chemotherapy Patients who are
disease free following surgery (e.g., stage III patients or solitary lymph node patients
following excisional biopsy) eligible No CNS disease Hormone receptor status: Not

PATIENT CHARACTERISTICS: Age: Physiologic 60 and under Menopausal status: Not specified
Performance status: ECOG 0 or 1 Life expectancy: Not specified Hematopoietic: Absolute
neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin at
least 8.0 g/dL Hepatic: Bilirubin less than 2.5 times normal unless due to Gilbert's
syndrome SGOT or SGPT less than 2.5 times normal Alkaline phosphatase less than 2.5 times
normal If hepatitis C antibody positive, then liver function must be normal OR liver
dysfunction must be due to metastatic disease and not chronic hepatitis Renal: Creatinine
less than 1.5 mg/dL OR Creatinine clearance greater than 50 mL/min Cardiovascular: LVEF at
least 50% unless cleared by cardiologist No myocardial infarction within the past 6 months
No significant arrhythmia requiring medications No congestive heart failure Pulmonary:
DLCO at least 50% predicted FEV1 and/or FVC at least 75% predicted unless due to
neoplastic pulmonary involvement No serious nonneoplastic pulmonary disease (severe
chronic obstructive lung disease) that would preclude study therapy Other: HIV negative
Hepatitis B and C surface antigen negative No active serious medical condition that would
preclude study therapy No allergy to Cremophor Not pregnant or nursing Negative pregnancy

PRIOR CONCURRENT THERAPY: No more than 3 prior treatment regimens for metastatic disease
Biologic therapy: Not specified Chemotherapy: See Disease Characteristics Prior
conventional dose chemotherapy as adjuvant or as treatment for advanced disease allowed
Prior doxorubicin greater than 450 mg/m2 allowed if dexrazoxane was used to reduce risk of
cardiotoxicity At least 3 weeks since prior chemotherapy Endocrine therapy: Not specified
Radiotherapy: No prior radiotherapy to indicator lesions At least 3 weeks since other
prior radiotherapy Surgery: See Disease Characteristics At least 3 weeks since prior

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Jane N. Winter, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Robert H. Lurie Cancer Center


United States: Federal Government

Study ID:

NU 96B1



Start Date:

October 1999

Completion Date:

May 2008

Related Keywords:

  • Breast Cancer
  • stage IV breast cancer
  • stage IIIA breast cancer
  • recurrent breast cancer
  • stage IIIB breast cancer
  • Breast Neoplasms



Robert H. Lurie Comprehensive Cancer Center, Northwestern University Chicago, Illinois  60611