Combination Chemotherapy in Treating Patients With High-Risk Breast Cancer

NCT ID: NCT00004092

Last Updated: 2015-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-05-31
• Study Completion Date: 2013-12-31

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: This randomized phase II trial is studying two different regimens of combination chemotherapy and comparing them to see how well they work in treating patients with high-risk primary stage II or stage III breast cancer.

Detailed Description

OBJECTIVES:

• Compare the toxic effects of doxorubicin, cyclophosphamide, and paclitaxel vs cyclophosphamide, thiotepa, and carboplatin in patients with high-risk primary breast cancer. (Arm I closed to accural as of 4/6/2006.)
• Compare the efficacies of these regimens followed by peripheral blood stem cell rescue in these patients.
• Determine the efficacy of a bisphosphonate to prevent relapse/metastasis after high-dose chemotherapy in these patients.

OUTLINE: This is a randomized study. Patients are stratified by stage of disease.

Peripheral blood stem cells (PBSC) are collected after mobilization with filgrastim (G-CSF), administered subcutaneously or IV, twice daily beginning 3 days before collection and continuing until collection is complete.

All patients receive conventional-dose adjuvant chemotherapy, probably comprising doxorubicin IV, cyclophosphamide IV, and fluorouracil IV over 1 hour on days 1, 22, 43, and 64. Patients are then randomized to receive 1 of 2 treatment arms of high-dose chemotherapy. (Arm I closed to accrual as of 4/6/2006.)

• Arm I (ACT) (closed to accrual as of 4/6/2006): Patients receive doxorubicin IV over 24 hours on days -9 to -6, cyclophosphamide IV over 2 hours on day -5, and paclitaxel IV over 24 hours on day -2. PBSC are reinfused on days -2 and 0. G-CSF is administered beginning on day 0 and continuing until blood counts recover.
• Arm II (STAMP V): Patients receive cyclophosphamide IV, carboplatin IV, and thiotepa IV over 24 hours on days -7 to -4. PBSC are reinfused and G-CSF is administered as in arm I.

Within 4-6 weeks of day 0 of high-dose chemotherapy, patients with estrogen and/or progesterone receptor positive tumors receive oral tamoxifen twice daily for 5 years. Patients are also randomized to receive a bisphosphonate comprising pamidronate IV every 4 weeks for 2 years.

Quality of life is assessed before therapy, at 30 days after high-dose chemotherapy, and at 6 and 12 months.

Patients are followed every 3 months for 1 year and then every 6 months for at least 10 years.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 3 years.

Conditions

Breast Cancer

Study Design

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

Study Groups

Arm I (ACT) (closed to accrual as of 4/6/2006)

Patients receive doxorubicin IV over 24 hours on days -9 to -6, cyclophosphamide IV over 2 hours on day -5, and paclitaxel IV over 24 hours on day -2. PBSC are reinfused on days -2 and 0. G-CSF is administered beginning on day 0 and continuing until blood counts recover.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

Given IV or subcutaneously

cyclophosphamide

Intervention Type: DRUG

Given IV

doxorubicin hydrochloride

Intervention Type: DRUG

Given IV

paclitaxel

Intervention Type: DRUG

Given IV

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Patients receive autologous peripheral blood stem cells

Arm II (STAMP V)

Patients receive cyclophosphamide IV, carboplatin IV, and thiotepa IV over 24 hours on days -7 to -4. PBSC are reinfused and G-CSF is administered as in arm I.

Group Type: ACTIVE_COMPARATOR

filgrastim

Intervention Type: BIOLOGICAL

Given IV or subcutaneously

carboplatin

Intervention Type: DRUG

Given IV

cyclophosphamide

Intervention Type: DRUG

Given IV

thiotepa

Intervention Type: DRUG

Given IV

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Patients receive autologous peripheral blood stem cells

Interventions

filgrastim

Given IV or subcutaneously

Intervention Type: BIOLOGICAL

carboplatin

Given IV

Intervention Type: DRUG

cyclophosphamide

Given IV

Intervention Type: DRUG

doxorubicin hydrochloride

Given IV

Intervention Type: DRUG

paclitaxel

Given IV

Intervention Type: DRUG

thiotepa

Given IV

Intervention Type: DRUG

peripheral blood stem cell transplantation

Patients receive autologous peripheral blood stem cells

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically proven high-risk primary breast cancer with less than 60% chance of progression-free survival of 3 years from diagnosis

• Stage II with at least 10 positive axillary nodes OR
• Stage IIIA or IIIB
• No histologically proven bone marrow metastasis
• No CNS metastasis
• Hormone receptor status:

• Hormone receptor status known

PATIENT CHARACTERISTICS:

Age:

• Physiological age 60 or under

Menopausal status:

• Not specified

Performance status:

• Karnofsky 80-100%

Life expectancy:

• See Disease Characteristics

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• SGOT or SGPT no greater than 2 times upper limit of normal
• Hepatitis B antigen negative

Renal:

• Creatinine no greater than 1.2 mg/dL
• Creatinine clearance at least 70 mL/min
• No prior hemorrhagic cystitis

Cardiovascular:

• Ejection fraction at least 55% by MUGA
• No prior significant valvular heart disease or arrhythmia

Pulmonary:

• FEV_1 at least 60% of predicted
• pO_2 at least 85 mm Hg on room air
• pCO_2 at least 43 mm Hg on room air
• DLCO at least 60% lower limit of predicted

Other:

• No other prior malignancy except squamous cell or basal cell skin cancer or stage I or carcinoma in situ of the cervix
• No CNS dysfunction that would preclude compliance
• HIV negative
• No sensitivity to E. coli-derived products
• Not pregnant
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 4 weeks since prior chemotherapy
• No prior doxorubicin of total dose exceeding 240 mg/m^2
• No prior paclitaxel of total dose of at least 750 mg/m^2
• No more than 12 months since prior conventional-dose adjuvant chemotherapy

Endocrine therapy:

• At least 4 weeks since prior hormonal therapy

Radiotherapy:

• At least 4 weeks since prior radiotherapy
• No prior radiation to the left chest wall

Surgery:

• Not specified

• 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

Banner Good Samaritan Medical Center

Phoenix, Arizona, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Countries

United States

Other Identifiers

U01CA063265

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-IRB-98096

Identifier Type: -

Identifier Source: secondary_id

CHNMC-PHII-18

Identifier Type: -

Identifier Source: secondary_id

NCI-H99-0038

Identifier Type: -

Identifier Source: secondary_id

CDR0000067305

Identifier Type: REGISTRY

Identifier Source: secondary_id

98096

Identifier Type: -

Identifier Source: org_study_id