Combination Chemotherapy in Treating Patients With High-Risk Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004092
• Other study ID #: 98096
• Secondary ID: U01CA063265P30CA
• Status: Completed
• Phase: Phase 2
• First received: December 10, 1999
• Last updated: July 7, 2015
• Start date: May 1999
• Est. completion date: December 2013

Study information

• Verified date: July 2015
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• filgrastim
Given IV or subcutaneously

Drug:
• carboplatin
Given IV
• cyclophosphamide
Given IV
• doxorubicin hydrochloride
Given IV
• paclitaxel
Given IV
• thiotepa
Given IV

Procedure:
• peripheral blood stem cell transplantation
Patients receive autologous peripheral blood stem cells

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Banner Good Samaritan Medical Center	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Five-Year Relapse-free Survival	RFS events included death or disease recurrence. Patients who did not experience disease recurrence or death were censored at the date of last follow-up. Survival rates were estimates using the Kaplan-Meier method.	Five years	No
Secondary	Five-Year Overall Survival	Patients who were still alive were censored at the date of last follow-up. Survival rates were estimates using the Kaplan-Meier method.	Five Years	No