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

NCT ID: NCT00003042

Last Updated: 2025-03-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-05-30
• Study Completion Date: 2025-12-29

Brief 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 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.

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

mesna

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

tamoxifen citrate

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

conventional surgery

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

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.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

mesna

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

tamoxifen citrate

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Interventions

filgrastim

Intervention Type: BIOLOGICAL

cisplatin

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

doxorubicin hydrochloride

Intervention Type: DRUG

melphalan

Intervention Type: DRUG

mesna

Intervention Type: DRUG

paclitaxel

Intervention Type: DRUG

tamoxifen citrate

Intervention Type: DRUG

bone marrow ablation with stem cell support

Intervention Type: PROCEDURE

conventional surgery

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George Somlo, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-96139

Identifier Type: -

Identifier Source: secondary_id

NCI-G97-1288

Identifier Type: -

Identifier Source: secondary_id

CDR0000065672

Identifier Type: REGISTRY

Identifier Source: secondary_id

96139

Identifier Type: -

Identifier Source: org_study_id