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A Pilot Trial of Sequential Chemotherapy With Antimetabolite Induction, High-Dose Alkylating Agent Consolidation With Peripheral Blood Progenitor Cell Support, and Intensification With Paclitaxel and Doxorubicin for Patients With High-Risk Breast Cancer

Phase 2
Not Enrolling
Breast Cancer, Breast Neoplasms

Thank you

Trial Information

A Pilot Trial of Sequential Chemotherapy With Antimetabolite Induction, High-Dose Alkylating Agent Consolidation With Peripheral Blood Progenitor Cell Support, and Intensification With Paclitaxel and Doxorubicin for Patients With High-Risk Breast Cancer

This pilot trial will examine the feasibility of administering induction high-dose therapy
with antimetabolites, followed with consolidation using high-dose single alkylating agent
therapy and finally intensification therapy with sequential cycles of very high doses of the
natural products (paclitaxel followed by doxorubicin) to patients with metastatic breast
cancer (stage IV), and to patients with lesser stage disease at high risk for relapse
(patients with four or more positive nodes (stage II), locally advanced breast cancer (stage
III)), and patients with locally or regionally recurrent breast cancer.

Patients will receive induction therapy with antimetabolite agents (methotrexate, leucovorin
and 5-fluorouracil) for four cycles. Patients will then receive consolidation therapy with
three cycles of high-dose alkylating agents. First, patients will receive one cycle of
high-dose cyclophosphamide administered with growth factor support. PBPCs will be harvested
during the recovery phase of the cyclophosphamide cycle.

The next cycle will consist of high-dose single agent thiotepa. Hematopoietic stem cells
mobilized and collected during the previous cyclophosphamide cycles will be reinfused
following treatment with thiotepa to augment recovery of bone marrow function. After
recovery, intensification with natural product chemotherapy will be administered, consisting
of four cycles of paclitaxel given as a 24-hour infusion followed by four cycles of single
agent doxorubicin.

This protocol combines several highly active chemotherapeutic agents in an attempt to
improve upon response rates achieved with current combinations. For high-risk stage II and
III patients, this chemotherapy regimen (without genetic manipulation of PBPCs) will serve
as a chemotherapy backbone onto which a companion immunotherapy protocol will be offered.
An identical chemotherapy regimen will be offered to stage four patients as a backbone for a
trial of retroviral transduction of the MDR1 and NeoR genes into harvested PBPCs.

Inclusion Criteria


Histologically proven AR and ESFT which includes: Classical, atypical and extraosseous
Ewing's sarcoma, primitive peripheral neuroectodermal tumors, peripheral neuroepithelioma,
primitive sarcoma of bone, and ectomesenchymoma.

Confirmed presence of tumor-specific infusion protein by documented RT-PCR which
corresponds to one of the tumor specific peptides available for vaccination.

Measurable tumor.

No prior or current CNS metastases.



May be enrolled on the protocol for the first phase in the absence of RT PCR documentation
of a tumor-specific fusion protein which corresponds to one of the tumor-specific peptides
available for vaccination. However, RT PCR documentation at the time of tumor recurrence
must occur prior to administration of immunotherapy. At time of initial tumor diagnosis,
prior to any cytoreductive therapy.


Tumor recurrence occurring during or after receiving at least first line cytoreductive
therapy for ESFT and AR. No more than two post-recurrence salvage regimens unless
peripheral CD4+T cell number is greater than 400 cells per millimeter cubed.

At least 6 weeks since any treatments and recovered from all acute toxic effects from time
in which immunotherapy will be started for this study.

No concurrent estrogen therapy during immunotherapy section of study.


Age: 2-25 (at time of initial diagnosis of alveolar rhabdomyosarcoma).

Weight: Greater than 15 kg (at time of apheresis).

Performance status: ECOG 0-2.

Life expectancy: At least 8 weeks.


ANC greater than 100,000/mm(3).

Hemoglobin greater than 9.0 g/dL.

Platelet count greater than 50,000/mm(3).


Bilirubin less than 2.0 mg/dL (unless related to involvement by tumor).

Transaminases less than 3 times normal (unless related to involvement by tumor).


Creatinine less than 1.5 mg/dL or creatinine clearance greater than 60 mL/min.


No major disorder of cardiovascular system.

Cardiac ejection fraction greater than 40%.


No major disorder of pulmonary system.


Not pregnant or nursing.

HIV negative.

Hepatitis B or C negative.

No patients requiring daily oral corticosteroid therapy.

If allergic to eggs, egg products, or thimerosal, or have a history of Guillain-Barre
syndrome, ineligible to receive influenza vaccine.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


United States: Federal Government

Study ID:




Start Date:

February 1996

Completion Date:

December 2000

Related Keywords:

  • Breast Cancer
  • Breast Neoplasms
  • 5-Fluorouracil
  • Cyclophosphamide
  • Methotrexate
  • Thiotepa
  • Breast Neoplasms
  • Neoplasms



National Cancer Institute (NCI) Bethesda, Maryland  20892