Full Text View
Tabular View
No Study Results Posted
Related Studies
Doxorubicin and Cyclophosphamide Plus Paclitaxel With or Without Trastuzumab in Treating Women With Node-Positive Breast Cancer That Overexpresses HER2
This study is ongoing, but not recruiting participants.
First Received: December 10, 1999   Last Updated: February 6, 2009   History of Changes
Sponsors and Collaborators: National Surgical Adjuvant Breast and Bowel Project (NSABP)
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00004067
  Purpose

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, cyclophosphamide, and 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 whether combination chemotherapy plus trastuzumab is more effective than combination chemotherapy alone for treating breast cancer.

PURPOSE: This randomized phase III trial is studying how well giving combination chemotherapy together with trastuzumab works compared to combination chemotherapy alone in treating women with node-positive stage II or stage IIIA breast cancer that overexpresses HER2.


Condition Intervention Phase
Breast Cancer
Biological: trastuzumab
Drug: AC-T regimen
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: endocrine drug therapy
Drug: paclitaxel
Drug: tamoxifen citrate
Radiation: radiation therapy
Phase III

Genetics Home Reference related topics: breast cancer
MedlinePlus related topics: Breast Cancer Cancer Radiation Therapy
Drug Information available for: Cyclophosphamide Tamoxifen Doxorubicin Doxorubicin hydrochloride Paclitaxel Tamoxifen citrate Myocet Trastuzumab
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: A Randomized Trial Comparing the Safety and Efficacy of Adriamycin and Cyclophosphamide Followed by Taxol (AC-T) to That of Adriamycin and Cyclophosphamide Followed by Taxol Plus Herceptin (AC-T+H) in Node-Positive Breast Cancer Patients Who Have Tumors That Overexpress HER2

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

Estimated Enrollment: 2700
Study Start Date: February 2000
Detailed Description:

OBJECTIVES:

  • Compare the cardiotoxicity of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab (Herceptin®) in women with operable, node-positive breast cancer that overexpresses HER2.
  • Compare the effect of these regimens on disease-free and overall survival of these patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to number of positive nodes (1-3 vs 4-9 vs 10 or more), administration of hormonal therapy (tamoxifen vs anastrozole vs neither), surgery/radiotherapy (lumpectomy plus breast irradiation vs lumpectomy plus breast irradiation plus regional irradiation vs mastectomy without radiotherapy vs mastectomy with radiotherapy), paclitaxel schedule (every 3 weeks vs weekly), and participating center. Patients are randomized to one of two treatment arms.

  • Arm I: Patients receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses. Approximately 3 weeks after the last course, patients receive paclitaxel IV over 3 hours every 21 days for 4 courses OR paclitaxel IV over 1 hour once weekly for 12 weeks (12 doses).
  • Arm II: Patients receive chemotherapy as in arm I and trastuzumab (Herceptin®) IV over 90 minutes on day 1 of the first course of paclitaxel.

Trastuzumab is then administered IV over 30 minutes weekly for 51 weeks, beginning on day 8.

All patients with estrogen or progesterone receptor-positive tumors receive hormonal therapy* for at least 5 years, beginning within 3-12 weeks after the last dose of chemotherapy. Patients who have received prior tamoxifen for prevention may be treated with additional tamoxifen for no more than 5 years at the discretion of the principal investigator (PI).

NOTE: *Other hormonal therapeutic agents are allowed in sequence with or as an alternative to tamoxifen therapy.

All patients previously treated with lumpectomy undergo breast irradiation beginning after completion of chemotherapy and concurrently with trastuzumab (in arm II) administration. Patients previously treated with mastectomy may also receive radiotherapy. Radiotherapy is administered daily for 5-6 weeks.

Patients are followed every 6 months for 5 years and then annually thereafter.

PROJECTED ACCRUAL: A total of 2,700 patients will be accrued for this study within 4.75 years.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically proven invasive adenocarcinoma of the breast

    • Stage IIA, IIB, or IIIA
    • Confined to the breast and ipsilateral axilla (cN0-1) on clinical examination
    • At least 1 histologically positive axillary node
    • No lymph nodes clinically fixed to each other or to other structures (cN2)
    • HER2 strongly positive (3+ by immunostain OR gene amplification by fluorescent in situ hybridization)

      • Submission of tumor block required
  • Must have undergone axillary dissection and either total mastectomy OR lumpectomy

    • Sentinel node dissection allowed, if followed by axillary dissection
    • No diffuse tumors by mammography in patients treated with lumpectomy
    • No more than 84 days since prior surgery for breast cancer (e.g., lumpectomy, mastectomy, axillary dissection, or re-excision of lumpectomy margins)
  • No bilateral malignancy, contralateral mass, or mammographic abnormality unless histologically proven as benign
  • No suspicious palpable nodes in the contralateral axilla or palpable supraclavicular or infraclavicular nodes unless histologically proven not to be involved with tumor
  • No primary T4 tumors (for any reason)
  • No prior breast cancer, including ductal carcinoma in situ

    • Prior lobular carcinoma in situ allowed
  • Bone pain allowed provided there is no metastatic disease by x-ray, MRI, or biopsy
  • Hormone receptor status:

    • Estrogen and progesterone status known

PATIENT CHARACTERISTICS:

Age:

  • Not specified

Sex:

  • Female

Menopausal status:

  • Not specified

Performance status:

  • Not specified

Life expectancy:

  • At least 10 years, excluding diagnosis of breast cancer

Hematopoietic:

  • Platelet count at least 100,000/mm^3*
  • Absolute neutrophil count at least 1,500/mm^3 (unless determined by the investigator to be normal for ethnic or racial variation) NOTE: *Significant underlying hematologic disorders must be excluded if above upper limit of normal (ULN)

Hepatic:

  • Bilirubin no greater than ULN
  • SGOT less than 1.5 times ULN
  • Alkaline phosphatase less than 2.5 times ULN
  • No systemic hepatic disease that would preclude study participation

Renal:

  • Creatinine normal
  • No systemic renal disease that would preclude study participation

Cardiovascular:

  • LVEF at least lower limit of normal by MUGA
  • No cardiovascular disease that would preclude study participation
  • No angina pectoris requiring treatment
  • No cardiomegaly on chest x-ray
  • No prior myocardial infarction by clinical diagnosis or by EKG or other test
  • No prior congestive heart failure
  • No prior cardiomyopathy
  • No cardiac arrhythmia requiring medication
  • No severe conduction abnormality
  • No clinically significant valvular disease
  • No poorly controlled hypertension (diastolic greater than 100 mm Hg), unless adequately controlled by medication
  • No ventricular hypertrophy on EKG

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective barrier contraception
  • No other prior malignancy within the past 5 years except effectively treated carcinoma in situ of the cervix, melanoma in situ, or basal cell or squamous cell skin cancer
  • No psychiatric or addictive disorders that would preclude informed consent
  • No sensory or motor neuropathy grade 2 or greater
  • No contraindications to corticosteroids

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior biologic therapy for this breast cancer

Chemotherapy:

  • No prior chemotherapy for this breast cancer
  • No prior anthracycline or taxane therapy for any cancer

Endocrine therapy:

  • No prior hormonal therapy for this breast cancer
  • No concurrent hormonal therapy (e.g., birth control pills or ovarian hormone replacement therapy)
  • No concurrent raloxifene or other selective estrogen-receptor modulators

Radiotherapy:

  • No prior radiotherapy for this breast cancer
  • No concurrent radiotherapy to internal mammary nodes
  • No other concurrent radiotherapy except as specified in study

Surgery:

  • See Disease Characteristics

Other:

  • No other concurrent investigational agents
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004067

  Show 149 Study Locations
Sponsors and Collaborators
National Surgical Adjuvant Breast and Bowel Project (NSABP)
Investigators
Study Chair: Edward H. Romond, MD Lucille P. Markey Cancer Center at University of Kentucky
  More Information

Additional Information:
Publications:
Rastogi P, Jeong J, Geyer CE, et al.: Five year update of cardiac dysfunction on NSABP B-31, a randomized trial of sequential doxorubicin/cyclophosphamide (AC)→paclitaxel (T) vs. AC→T with trastuzumab(H). [Abstract] J Clin Oncol 25 (Suppl 18): A-LBA513, 2007.
Geyer CE, Bryant JL, Romond EH, et al.: Update of cardiac dysfunction on NSABP B-31, a randomized trial of sequential doxorubicin/cyclophosphamide (AC)→paclitaxel (T) vs. AC→T with trastuzumab (H). [Abstract] J Clin Oncol 24 (Suppl 18): A-581, 2006.
Kim C, Bryant J, Horne Z, et al.: Trastuzumab sensitivity of breast cancer with co-amplification of HER2 and cMYC suggests pro-apoptotic function of dysregulated cMYC in vivo. [Abstract] Breast Cancer Research and Treatment 94 (Suppl 1): A-46, 2005.
Tan-Chiu E, Yothers G, Romond E, Geyer CE Jr, Ewer M, Keefe D, Shannon RP, Swain SM, Brown A, Fehrenbacher L, Vogel VG, Seay TE, Rastogi P, Mamounas EP, Wolmark N, Bryant J. Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31. J Clin Oncol. 2005 Nov 1;23(31):7811-9.
Geyer CE Jr, Bryant J, Romond E: Cardiac safety analysis of the first stage of NSABP B-31, a randomized trial comparing the safety and efficacy of adriamycin® and cyclophosphamide (AC) followed by taxol® to that of AC followed by taxol® plus herceptin® in patients (Pts) with operable, node-positive (N+), HER-2 overexpressing breast cancer (HER2+BC). [Abstract] Breast Cancer Res Treat 82 (Suppl 1): A-23, S13, 2003.
Paik S, Bryant J, Tan-Chiu E, Romond E, Hiller W, Park K, Brown A, Yothers G, Anderson S, Smith R, Wickerham DL, Wolmark N. Real-world performance of HER2 testing--ational Surgical Adjuvant Breast and Bowel Project experience. J Natl Cancer Inst. 2002 Jun 5;94(11):852-4.
Jahanzeb M. Adjuvant trastuzumab therapy for HER2-positive breast cancer. Clin Breast Cancer. 2008 Aug;8(4):324-33.
Reinholz MM, Dueck AC, Lingle WL, et al.: The concordance between NCCTG's and NSABP's C-myc FISH assays. [Abstract] J Clin Oncol 26 (Suppl 15): A-22110, 2008.
Garrison LP Jr, Lubeck D, Lalla D, Paton V, Dueck A, Perez EA. Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2-positive breast cancer. Cancer. 2007 Jun 25; [Epub ahead of print]
Kurian AW, Thompson RN, Gaw AF, Arai S, Ortiz R, Garber AM. A cost-effectiveness analysis of adjuvant trastuzumab regimens in early HER2/neu-positive breast cancer. J Clin Oncol. 2007 Feb 20;25(6):634-41.
Liberato NL, Marchetti M, Barosi G. Cost effectiveness of adjuvant trastuzumab in human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2007 Feb 20;25(6):625-33.
Perez E, Romond E, Suman V, et al.: Updated results of the combined analysis of NCCTG N9831 and NSABP B-31 adjuvant chemotherapy with/without trastuzumab in patiens with HER2-positive breast cancer. [Abstract] J Clin Oncol 25 (Suppl 18): 512, 6s, 2007.
Telli ML, Hunt SA, Carlson RW, Guardino AE. Trastuzumab-related cardiotoxicity: calling into question the concept of reversibility. J Clin Oncol. 2007 Aug 10;25(23):3525-33.
Baselga J, Perez EA, Pienkowski T, Bell R. Adjuvant trastuzumab: a milestone in the treatment of HER-2-positive early breast cancer. Oncologist. 2006;11 Suppl 1:4-12. Review.
Garrison LP, Perez EA, Dueck A, et al.: Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2+ breast cancer. [Abstract] J Clin Oncol 24 (Suppl 18): A-6023, 306s, 2006.
Gupta AK, Mekan SF, Eckman MH: Trastuzumab for all? A decision analysis examining tradeoffs between efficacy and cardiac toxicity of adjuvant therapy in HER2 positive breast cancer. [Abstract] J Clin Oncol 24 (Suppl 18): A-6022, 306s, 2006.
Burstein HJ. The distinctive nature of HER2-positive breast cancers. N Engl J Med. 2005 Oct 20;353(16):1652-4. No abstract available.
Hortobagyi GN. Trastuzumab in the treatment of breast cancer. N Engl J Med. 2005 Oct 20;353(16):1734-6. No abstract available.
Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE Jr, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN, Wolmark N. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1673-84.
Tan-Chiu E, Piccart M. Moving forward: Herceptin in the adjuvant setting. Oncology. 2002;63 Suppl 1:57-63. Review.

Study ID Numbers: CDR0000067269, NSABP-B-31
Study First Received: December 10, 1999
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00004067     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage II breast cancer
stage IIIA breast cancer

Study placed in the following topic categories:
Immunologic Factors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Cyclophosphamide
Selective Estrogen Receptor Modulators
Hormones
Anti-Bacterial Agents
Estrogen Receptor Modulators
Trastuzumab
Alkylating Agents
Breast Diseases
Estrogens
Estrogen Antagonists
Skin Diseases
Antineoplastic Agents, Hormonal
Citric Acid
Breast Neoplasms
Antimitotic Agents
Immunosuppressive Agents
Tamoxifen
Doxorubicin
Paclitaxel
Tubulin Modulators
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

Additional relevant MeSH terms:
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Cyclophosphamide
Antibiotics, Antineoplastic
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Neoplasms by Site
Therapeutic Uses
Trastuzumab
Alkylating Agents
Breast Diseases
Estrogen Antagonists
Skin Diseases
Antineoplastic Agents, Hormonal
Mitosis Modulators
Breast Neoplasms
Antimitotic Agents
Immunosuppressive Agents
Tamoxifen
Doxorubicin
Pharmacologic Actions
Neoplasms
Paclitaxel
Tubulin Modulators
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 07, 2009