Combination Chemotherapy in Treating Patients With High-Risk Breast Cancer

Condition(s) targeted: Breast Cancer

Intervention: carboplatin (Drug); cyclophosphamide (Drug); doxorubicin hydrochloride (Drug); filgrastim (Drug); paclitaxel (Drug); thiotepa (Drug); peripheral blood stem cell transplantation (Procedure)

Phase: Phase 2

Status: Recruiting

Sponsored by: Beckman Research Institute

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.

Official title: Randomized Phase II Study of Adriamycin/Cytoxan/Taxol (ACT) vs. Cytoxan, Thiotepa, Carboplatin (STAMP V) in Patients With High-Risk Primary Breast Cancer

Study design: Treatment, Randomized, Active Control

Primary outcome:

Disease-free survival

Incidence of grade IV toxicity

Secondary outcome:

Overall survival

Treatment-related mortality

Time to engraftment

Time to platelet independence

Reduction in the degree of developing osteoporosis

Toxicity profile

Incidence of novel clonal hematopoietic abnormalities

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.

Minimum age: N/A. Maximum age: 60 Years. Gender(s): Both.

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

Banner Good Samaritan Medical Center, Phoenix, Arizona 85006, United States; Recruiting
Jeffrey R. Schriber, MD, Phone: 602-239-4526, Email: jeffrey.schriber@bannerhealth.com

City of Hope Comprehensive Cancer Center, Duarte, California 91010-3000, United States; Recruiting
Clinical Trials Office - City of Hope Comprehensive Cancer Cen, Phone: 800-826-4673, Email: becomingapatient@coh.org

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: May 1999
Last updated: October 22, 2008