Combination Chemotherapy in Treating Patients With High-Risk Breast Cancer - Full Text View

Sponsor:	Beckman Research Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00004092

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Biological: filgrastim Drug: carboplatin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel Drug: thiotepa Procedure: peripheral blood stem cell transplantation	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Thiotepa Doxorubicin Doxorubicin hydrochloride Paclitaxel Carboplatin Myocet Filgrastim

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Disease-free survival [ Designated as safety issue: No ]
Incidence of grade IV toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Treatment-related mortality [ Designated as safety issue: Yes ]
Time to engraftment [ Designated as safety issue: No ]
Time to platelet independence [ Designated as safety issue: No ]
Reduction in the degree of developing osteoporosis [ Designated as safety issue: No ]
Toxicity profile [ Designated as safety issue: Yes ]
Incidence of novel clonal hematopoietic abnormalities [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	May 1999
Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I (ACT) (closed to accrual as of 4/6/2006): Experimental 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.	Biological: filgrastim Given IV or subcutaneously Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: paclitaxel Given IV Procedure: peripheral blood stem cell transplantation Patients receive autologous peripheral blood stem cells
Arm II (STAMP V): Active Comparator 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.	Biological: filgrastim Given IV or subcutaneously Drug: carboplatin Given IV Drug: cyclophosphamide Given IV Drug: thiotepa Given IV Procedure: peripheral blood stem cell transplantation Patients receive autologous peripheral blood stem cells

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.

Eligibility

Ages Eligible for Study:	up to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004092

Locations

United States, Arizona
Banner Good Samaritan Medical Center
Phoenix, Arizona, United States, 85006
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000

Sponsors and Collaborators

Beckman Research Institute

National Cancer Institute (NCI)

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	City of Hope Comprehensive Cancer Center ( George Somlo )
Study ID Numbers:	CDR0000067305, CHNMC-IRB-98096, CHNMC-PHII-18, NCI-H99-0038
Study First Received:	December 10, 1999
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00004092 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:

Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Neoplasms by Site
Therapeutic Uses
Alkylating Agents
Breast Diseases
Skin Diseases
Mitosis Modulators
Breast Neoplasms

Carboplatin
Antimitotic Agents
Immunosuppressive Agents
Doxorubicin
Pharmacologic Actions
Thiotepa
Neoplasms
Paclitaxel
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on November 09, 2009