RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if paclitaxel is more effective with or without carboplatin in treating stage IV breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of paclitaxel with or without carboplatin in treating women who have stage IV breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Procedure: chemotherapy  Drug: carboplatin  Drug: paclitaxel	Phase III

Further Study Details: 

OBJECTIVES: I. Compare the objective response rate in women treated with paclitaxel with or without carboplatin as first-line chemotherapy for metastatic breast cancer. II. Compare the overall survival, time to disease progression, and duration of response in these patients treated with these regimens. III. Compare the safety of these regimens in this patient population. IV. Compare the quality of life of these patients treated with these regimens.

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior adjuvant chemotherapy (yes vs no) and ECOG performance status (0-1 vs 2). Patients are randomized to one of two treatment arms. Arm I: Patients receive paclitaxel IV over 1 hour weekly for 3 weeks. Arm II: Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes weekly for 3 weeks. Treatment in both arms continues every 4 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, before each course during study, and then after completion of study. Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 220 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically or cytologically confirmed breast cancer

• Must have clinical evidence of stage IV (M1) disease

HER-2/neu negative (0, 1+, or 2+ by immunohistochemistry or fluorescent in situ hybridization) OR status unknown

At least 1 measurable lesion

• At least 20 mm by conventional techniques OR At least 10 mm by spiral CT scan
• Patients with bone-only disease are not eligible

Ineligible if currently experiencing a complete or partial response to prior hormonal therapy

Patients with disease progression after prior response to hormonal therapy are eligible

Disease progression without prior hormonal therapy is allowed

Stable or asymptomatic brain metastasis allowed if:

• Other measurable disease exists
• Cranial irradiation completed and brain metastasis stable for at least 4 weeks before study

Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

Biologic therapy:

• More than 6 months since prior adjuvant bone marrow or peripheral blood stem cell transplantation
• More than 6 months since prior adjuvant monoclonal antibody therapy
• More than 6 months since prior adjuvant vaccine therapy
• No prior trastuzumab (Herceptin)
• No concurrent anticancer immunotherapy

Chemotherapy:

• No prior chemotherapy for metastatic breast cancer
• More than 6 months since prior adjuvant high-dose chemotherapy
• More than 6 months since prior adjuvant taxanes or any other adjuvant chemotherapy
• Prior adjuvant taxanes allowed only if administered every 3 weeks

Endocrine therapy:

• See Disease Characteristics
• Any number of prior hormonal therapies for metastatic breast cancer allowed (Patients with definite signs of progression may begin study therapy immediately after stopping hormonal therapy)
• No concurrent anticancer hormonal agents (including megestrol)

Radiotherapy:

• At least 3 weeks since prior radiotherapy (4 weeks for cranial irradiation)
• No prior radiotherapy to 30% or more of bone marrow
• No concurrent radiotherapy except for palliation of painful bone metastasis or pathologic fractures to the area of known lytic disease

Surgery: At least 3 weeks since prior major surgery

Other:

• More than 6 months since prior neoadjuvant therapy
• No other concurrent anticancer drugs

--Patient Characteristics--

Age: 18 and over

Sex: Female

Menopausal status: Pre- or post-menopausal

Performance status: ECOG 0-2

Life expectancy: At least 3 months

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST and ALT no greater than 2 times ULN

Renal:

• Creatinine no greater than 2 times ULN
• Corrected calcium less than 12 mg/dL

Cardiovascular:

• No New York Heart Association class III or IV heart disease
• No documented myocardial infarction within the past 6 months
• No congestive heart failure
• No unstable angina
• No clinically significant pericardial effusion or arrhythmia

Other:

• No active serious infection
• No prior significant allergic reactions to drugs containing Cremophor, such as teniposide, cyclosporine, or vitamin K
• No clinically significant (greater than grade 1) peripheral neuropathy
• No other serious underlying medical condition that would preclude study

Arkansas
      Highlands Oncology Group, Springdale,  Arkansas,  72764,  United States
California
      Monterey Bay Oncology, Monterey,  California,  93940,  United States
      University of California Davis Cancer Center, Sacramento,  California,  95817,  United States
      Wilshire Oncology Medical Group, Inc., Pomona,  California,  91767-3021,  United States
Connecticut
      New Britain General Hospital, New Britain,  Connecticut,  06050,  United States
Florida
      Cancer Research Network, Inc., Hollywood,  Florida,  33020,  United States
      Center for Hematology and Oncology, Boca Raton,  Florida,  33486,  United States
      Mayo Clinic, Jacksonville,  Florida,  32224,  United States
Illinois
      MacNeal Cancer Center, Berwyn,  Illinois,  60402,  United States
      Oncology Specialists, SC, Park Ridge,  Illinois,  60068,  United States
Maine
      Maine Center for Cancer Medicine and Blood Disorders, Scarborough,  Maine,  04074,  United States
Maryland
      Maryland Hematology/Oncology Associates, Baltimore,  Maryland,  21236,  United States
Missouri
      St. John's Mercy Medical Center, Saint Louis,  Missouri,  63141,  United States
New Jersey
      St. Barnabas Medical Center, Livingston,  New Jersey,  07039,  United States
New York
      Finger Lakes Community Cancer Center, Clifton Springs,  New York,  14432,  United States
Ohio
      Clinical Hematology & Oncology Service, Inc., Akron,  Ohio,  44302,  United States
Pennsylvania
      Scranton Hematology-Oncology, Scranton,  Pennsylvania,  18510,  United States
Tennessee
      East Tennessee Oncology/Hematology, P.C., Knoxville,  Tennessee,  37920,  United States
      West Clinic, Memphis,  Tennessee,  38120,  United States
Texas
      Oncology Consultants, Houston,  Texas,  77024,  United States
      Scott and White Clinic, Temple,  Texas,  76508,  United States
      Texas Cancer Care, Fort Worth,  Texas,  76104,  United States
Virginia
      Northern Virginia Oncology Group, P.C., Fairfax,  Virginia,  22031,  United States
Washington
      Seattle Cancer Care Alliance, Seattle,  Washington,  98109,  United States
Wisconsin
      Dean Medical Center, Madison,  Wisconsin,  53715,  United States

Study chairs or principal investigators

Edith A. Perez,  Study Chair,  Theradex   

Study ID Numbers:  CDR0000068992; THERADEX-B00-1370; BMS-TAX/MEN.13
Record last reviewed:  August 2003
Last Updated:  October 13, 2004
Record first received:  October 11, 2001
ClinicalTrials.gov Identifier:  NCT00025688
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08