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Combination Chemotherapy in Treating Patients With High-Risk Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00004092
First received: December 10, 1999
Last updated: November 26, 2012
Last verified: November 2012
History of Changes
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
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:

U.S. FDA Resources

Further study details as provided by City of Hope Medical Center:

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
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
 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
Active Comparator: 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.
 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
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: George Somlo, MD City of Hope Medical Center
  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 Medical Center
ClinicalTrials.gov Identifier: NCT00004092     History of Changes
Other Study ID Numbers: 98096, U01CA063265, P30CA033572, CHNMC-IRB-98096, CHNMC-PHII-18, NCI-H99-0038, CDR0000067305
Study First Received: December 10, 1999
Last Updated: November 26, 2012
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Thiotepa
Doxorubicin
Carboplatin
Paclitaxel
Lenograstim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
 Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on May 22, 2013