Chemotherapy and Stem Cell Transplantation in Treating Patients With Stage IIIB Breast Cancer

March 29, 2024 updated by: City of Hope Medical Center

Dose-Intense Chemotherapy and Stem Cell Rescue in the Treatment of Inflammatory Breast Carcinoma

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 drugs and kill more tumor cells.

PURPOSE: This phase II trial is studying how well chemotherapy and stem cell transplantation work in treating patients with stage IIIB breast cancer.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

  • Determine the effectiveness of neoadjuvant dose intensive sequential chemotherapy, followed by surgical resection, adjuvant therapy, and tandem high dose chemotherapy and stem cell rescue in patients with inflammatory stage IIIB breast cancer.
  • Determine the clinical and pathological remission rate (complete, partial, and overall) following neoadjuvant dose dependent sequential chemotherapy in patients with inflammatory stage IIIB breast cancer.
  • Determine the relapse and survival rate of these patients with the above therapy.
  • Determine the potential correlations between inflammatory features and hereditary background.

OUTLINE: Patients are stratified according to those who have had no more than 1 cycle of neoadjuvant chemotherapy (stratum 1) and those who have had more than 1 cycle of neoadjuvant chemotherapy and/or modified radical mastectomy (stratum 2).

Patients in stratum 1 receive doxorubicin IV over 96 hours on days 1-4, 15-19, and 29-32. Paclitaxel is infused over 96 hours on days 43-47 and 57-60. Filgrastim (G-CSF) is administered on days 5-10, 20-25, 33-38, 48-55, and 61-68, and beyond if the granulocyte count is less than 1000/mm^3. A modified radical mastectomy is performed between days 70 and 80. All stratum 1 and stratum 2 patients then receive paclitaxel IV for 96 hours on days 100-104, and cyclophosphamide IV on day 121. Filgrastim is administered at one dose on days 105-110 and days 122-127 and at a higher dose on days 110-116 and days 128-135. Stem cells are harvested from the patient on days 113-116 and days 132-135.

High-dose chemotherapy is then administered to all patients in the study. Course 1 starts with doxorubicin IV on days -7 to -3. Paclitaxel IV is administered for 24 hours on day -2. Filgrastim is administered by IV on day -1 and continued until the granulocyte count is greater than 1000/mm^3 for 3 days. Peripheral stem cells are reinfused on day 0. Course 2 starts 4-6 weeks after the start of course 1 with melphalan and cisplatin being infused on day -11. Filgrastim is administered IV on days -10 to -6. Melphalan and cisplatin are administered again on day -4. Stem cells are infused on day -3 and on day 0. Filgrastim is then administered until the granulocyte count is at least 1000/mm^3 for 3 days.

Radiation therapy is started 4-7 weeks after the beginning of course 2. Tamoxifen is started within 2 weeks of discharge following course 2 in patients with hormone receptor positive tumors.

Patients are followed every 3 months for two years and then annually for the next three years.

PROJECTED ACCRUAL: Approximately 60 patients will be accrued, at a rate of about 15 per year.

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Description

DISEASE CHARACTERISTICS:

  • Histologically proven stage IIIB breast cancer with dermal/epidermal invasion or clinical features of inflammation, erythema, pain or hypersensitivity, edema, or thickening of the skin
  • Diagnosis within the past 6 months

PATIENT CHARACTERISTICS:

Age:

  • 60 and under

Performance status:

  • Karnofsky 80-100%

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin less than 1.5 mg/dL
  • SGOT or SGPT no greater than 1.5 times the upper limit of normal

Renal:

  • Creatinine less than 1.2 mg/dL
  • Creatinine clearance at least 80 mL/min
  • No history of hemorrhagic cystitis

Cardiovascular:

  • Left ventricular fraction at least 55% on MUGA scan
  • No previous valvular heart disease or arrhythmia

Pulmonary:

  • FEV_1 at least 60% predicted
  • Room air pO_2 greater than 85 mmHg
  • Room air pCO_2 no greater than 43 mmHg
  • DLCO at least 60% of the lower limit of predicted value

Other:

  • No history of malignant disease in the past 5 years, except for squamous or basal cell skin cancer and stage I or in situ cervical cancer
  • No organic CNS dysfunction
  • Not pregnant
  • No known and potentially disabling psychosocial history
  • Not positive for hepatitis B or HIV

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • Stratum 1:

    • No more than one cycle of chemotherapy

  • Stratum 2:

    • No greater than 225 mg/m^2 doxorubicin and no greater than 250 mg/m^2 paclitaxel during previous chemotherapy

Endocrine therapy:

  • Not specified

Radiotherapy:

  • No prior radiation to the left chest wall

Surgery:

  • Modified radical mastectomy allowed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1 cycle of neoadjuvant chemotherapy
Patients receive chemotherapy, surgical removal of the cancer followed by additional chemotherapy, followed by two treatment cycles of very high-dose chemotherapy, return of bone marrow derived cells, followed by radiation therapy and if indicated five years of tamoxifen treatment.
Drug: cyclophosphamide
Drug: cisplatin
Drug: doxorubicin hydrochloride
Procedure: conventional surgery
Procedure: peripheral blood stem cell transplantation
Drug: paclitaxel
Biological: filgrastim
Drug: melphalan
Drug: tamoxifen citrate
Drug: mesna
Procedure: bone marrow ablation with stem cell support
Experimental: More than 1 cycle of neoadjuvant chemotherapy
Patients receive chemotherapy, followed by two treatment cycles of very high-dose chemotherapy, return of bone marrow derived cells, followed by radiation therapy and if indicated five years of tamoxifen treatment.
Drug: cisplatin
Drug: doxorubicin hydrochloride
Procedure: peripheral blood stem cell transplantation
Drug: paclitaxel
Biological: filgrastim
Drug: melphalan
Drug: tamoxifen citrate
Drug: mesna
Procedure: bone marrow ablation with stem cell support

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Three-year Relapse-free Survival
Time Frame: From date of mastectomy until date of relapse or death from any cause, 3 years post mastectomy.
Estimated using the product-limit method of Kaplan and Meier. Relapse defined as appearance of any new lesions during or after protocol treatment.
From date of mastectomy until date of relapse or death from any cause, 3 years post mastectomy.
Five-year Overall Survival
Time Frame: From date of mastectomy until date of death, 5 years post mastectomy.
Estimated using the product-limit method of Kaplan and Meier. Endpoint is defined as death due to any cause.
From date of mastectomy until date of death, 5 years post mastectomy.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: George Somlo, MD, City of Hope Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 30, 1997

Primary Completion (Actual)

February 9, 2010

Study Completion (Estimated)

December 30, 2024

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

January 26, 2003

First Posted (Estimated)

January 27, 2003

Study Record Updates

Last Update Posted (Actual)

April 2, 2024

Last Update Submitted That Met QC Criteria

March 29, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 96139
  • P30CA033572 (U.S. NIH Grant/Contract)
  • CHNMC-96139
  • NCI-G97-1288
  • CDR0000065672 (Registry Identifier: NCI PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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