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Paclitaxel With or Without Trastuzumab in Treating Women With Inoperable, Recurrent, or Metastatic Breast Cancer With or Without Overexpression of HER2/Neu
This study has been completed.
First Received: November 1, 1999   Last Updated: June 6, 2009   History of Changes
Sponsors and Collaborators: Cancer and Leukemia Group B
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003440
  Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known which of two regimens of paclitaxel, with or without trastuzumab, is more effective in treating women with inoperable, recurrent, or metastatic breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two regimens of paclitaxel, with or without trastuzumab, in treating women who have breast cancer that is inoperable, recurrent, or metastatic, with or without overexpression of HER2/neu.


Condition Intervention Phase
Breast Cancer
 Biological: trastuzumab
Drug: paclitaxel
 Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: A Phase III Study of Paclitaxel Via Weekly One Hour Infusion Versus Standard Three Hour Infusion Every Three Weeks in the Treatment of Patients With Metastatic Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer
Drug Information available for: Paclitaxel Trastuzumab
U.S. FDA Resources

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

Estimated Enrollment: 580
Study Start Date: July 1998
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Compare the response rate in women with inoperable, recurrent, or metastatic breast cancer treated with paclitaxel via one-hour infusion every week vs 3-hour infusion every 3 weeks, regardless of HER2/neu status and assignment to trastuzumab (Herceptin®).
  • Compare the response rate and quality of life of patients with HER2/neu-nonoverexpressing disease treated with 1 of these 2 paclitaxel regimens with or without trastuzumab.
  • Correlate amplification and overexpression of the growth factor receptor ErbB2 by immunohistochemistry and fluorescent in situ hybridization (FISH) with response rate, time to progression, and overall survival of patients treated with these regimens.
  • Correlate ErbB2 shed extracellular domain (ECD) with response rate, time to progression, and overall survival of patients treated with these regimens.
  • Assess the patterns of ErbB2/ECD after treatment with these regimens and upon relapse in these patients.
  • Compare the time to progression and survival of patients with HER2/neu-overexpressing disease treated with these regimens.
  • Compare the time to progression and survival of patients with HER2/neu-nonoverexpressing disease treated with these regimens.
  • Compare the cardiac toxicity of these regimens as measured by changes in left ventricular ejection fraction from baseline to follow-up measurements in these patients.

OUTLINE: This is a randomized study. Patients are stratified according to prior chemotherapy for metastatic disease (none or recurrence more than 6 months after adjuvant therapy vs one or none but recurrence less than 6 months after adjuvant therapy) and HER2/neu overexpression (yes vs no). Patients are assigned to 1 of 2 treatment groups based on HER2/neu status.

  • Group A (HER2/neu-nonoverexpressing): Patients are randomized to 1 of 4 treatment arms.

    • Arm I: Patients receive paclitaxel IV over 3 hours on day 1.
    • Arm II: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15.
    • Arm III: Patients receive paclitaxel as in arm I. Patients receive an initial loading dose of trastuzumab (Herceptin®) IV over 90 minutes on day 1 of course 1 and maintenance dose of trastuzumab IV over 30 minutes on day 1 of subsequent courses and on days 8 and 15 of all courses. Trastuzumab is administered immediately after completion of paclitaxel infusion on weeks of concurrent administration.
    • Arm IV: Patients receive paclitaxel as in arm II and trastuzumab as in arm III.

  • Group B: (HER2/neu-overexpressing): Patients are randomized to 1 of 2 treatment arms.

    • Arm I: Patients receive treatment as in arm III (group A).
    • Arm II: Patients receive treatment as in arm IV (group A). In both groups, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then at 3, 6, and 9 months.

Patients are followed at 6, 12, and 18 months and then annually for 5 years or until death.

PROJECTED ACCRUAL: A total of 580 patients will be accrued for this study within 3 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically proven inoperable, recurrent, or metastatic adenocarcinoma of the breast
  • Known HER2/neu status
  • Measurable disease
  • No CNS metastases unless at least 6 months since prior cranial radiotherapy and the patient is asymptomatic and not receiving corticosteroids for this condition at time of enrollment
  • No leptomeningeal carcinoma (carcinomatous meningitis)

  • Hormone receptor status:

    • Not specified

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Sex:

  • Female

Menopausal status:

  • Not specified

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3

Hepatic:

  • Bilirubin normal
  • SGOT no greater than 3 times upper limit of normal

Renal:

  • Creatinine no greater than 2.0 mg/dL

Cardiovascular:

  • Left ventricular ejection fraction at least 45%

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior trastuzumab (Herceptin®)
  • Concurrent epoetin alfa allowed

Chemotherapy:

  • No more than 1 prior chemotherapy regimen for locally advanced or metastatic breast cancer
  • No prior taxane for locally advanced or metastatic breast cancer
  • No more than 1 prior adjuvant chemotherapy regimen
  • At least 12 months since prior adjuvant taxane and recovered
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, melphalan, or mitomycin)
  • No other concurrent chemotherapy

Endocrine therapy:

  • See Disease Characteristics
  • More than 4 weeks since prior hormonal therapy
  • More than 1 week since prior hormonal therapy if documented tumor progression

  • No concurrent hormonal therapy except any of the following:

    • Steroids for documented CNS metastases, adrenal failure, septic shock, or prevention of serious allergic reaction or emesis
    • Hormonal therapy for nonmalignant conditions (e.g., insulin for diabetes)

Radiotherapy:

  • See Disease Characteristics
  • No concurrent radiotherapy except whole brain irradiation for CNS disease

Surgery:

  • More than 2 weeks since prior surgery, other than biopsy or placement of venous access device

Other:

  • Concurrent bisphosphonate (e.g., pamidronate) therapy allowed
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003440

  Show 74 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
National Cancer Institute (NCI)
Investigators
Study Chair: Andrew D. Seidman, MD Memorial Sloan-Kettering Cancer Center
  More Information

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

Publications:
Rimm DL, Broadwater G, Friedman P, et al.: Uniformly positive (>80%) HER2 expression maximizes sensitivity and specificity for prediction of response to trastuzumab in CALGB 9840. [Abstract] 31st Annual San Antonio Breast Cancer Symposium, December 10-14, 2008, San Antonio, Texas. A-6046, 2008.
Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, Gipson G, Burstein H, Lake D, Shapiro CL, Ungaro P, Norton L, Winer E, Hudis C. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008 Apr 1;26(10):1642-9.
Naughton MJ, Gu L, Wang XF, et al.: Quality of life (QOL) companion to CALGB 9840: a phase III study of paclitaxel (P) via weekly 1 hour (hr) versus standard 3 hour infusion every 3 weeks with trastuzumab in the treatment of patients with/without HER-2/neu-overexpressing metastatic breast cancer. [Abstract] J Clin Oncol 24 (Suppl 18): A-674, 2006.
Seidman AD, Broadwater G, Carney W, et al.: Serum HER2 extracellular domain (ECD) levels and efficacy of weekly (W) or every 3-weekly (q3W) paclitaxel (P) with or without trastuzumab (T) in patients (pts) with metastatic breast cancer (MBC): CALGB 150002/9840. [Abstract] J Clin Oncol 23 (Suppl 16): A-558, 18s, 2005.
Seidman AD, Berry D, Cirrincione C, et al.: CALGB 9840: phase III study of weekly (W) paclitaxel (P) via 1-hour(h) infusion versus standard (S) 3h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (T) for HER2 positive MBC and randomized for T in HER2 normal MBC. [Abstract] J Clin Oncol 22 (Suppl 14): A-512, 6s, 2004.
Polite BN, Cirrincione C, Fleming GF, Berry DA, Seidman A, Muss H, Norton L, Shapiro C, Bakri K, Marcom K, Lake D, Schwartz JH, Hudis C, Winer EP. Racial differences in clinical outcomes from metastatic breast cancer: a pooled analysis of CALGB 9342 and 9840--Cancer and Leukemia Group B. J Clin Oncol. 2008 Jun 1;26(16):2659-65.
Kaufman PA, Broadwater G, Lezon-Geyda K, et al.: CALGB 150002: correlation of HER2 and chromosome 17 (ch17) copy number with trastuzumab (T) efficacy in CALGB 9840, paclitaxel (P) with or without T in HER2+ and HER2- metastatic breast cancer (MBC). [Abstract] J Clin Oncol 25 (Suppl 18): A-1009, 2007.
Polite BN, Cirrincione C, Fleming GF, et al.: Understanding racial differences in outcome from metastatic breast cancer (MBC): a pooled analysis of Cancer and Leukemia Group B (CALGB) 9342 and 9840. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-3097, 2005.

Study ID Numbers: CDR0000066468, CLB-9840
Study First Received: November 1, 1999
Last Updated: June 6, 2009
ClinicalTrials.gov Identifier: NCT00003440     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage IV breast cancer
recurrent breast cancer
stage IIIB breast cancer

Study placed in the following topic categories:
Skin Diseases
Paclitaxel
Tubulin Modulators
Trastuzumab
Breast Neoplasms
 Antimitotic Agents
Antineoplastic Agents, Phytogenic
Breast Diseases
Recurrence

Additional relevant MeSH terms:
Skin Diseases
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Mitosis Modulators
Breast Neoplasms
Antimitotic Agents
Pharmacologic Actions
Neoplasms
 Neoplasms by Site
Paclitaxel
Therapeutic Uses
Tubulin Modulators
Trastuzumab
Antineoplastic Agents, Phytogenic
Breast Diseases

ClinicalTrials.gov processed this record on September 01, 2009



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