Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

Further Study Information

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.

Eligibility 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

Trial Contact Information

Trial Lead Organizations/Sponsors

City of Hope Comprehensive Cancer Center

George Somlo

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00004092
Information obtained from ClinicalTrials.gov on December 14, 2011

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