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Chemotherapy Plus Monoclonal Antibody Therapy in Treating Women With Stage II or Stage IIIA Breast Cancer That Overexpresses HER2

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003992
First received: November 1, 1999
Last updated: May 31, 2013
Last verified: March 2013
  Purpose

Randomized phase II trial to study the effectiveness of chemotherapy with paclitaxel and the monoclonal antibody trastuzumab followed by chemotherapy in treating women who have stage II or stage IIIA breast cancer that overexpresses HER2. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells.


Condition Intervention Phase
Breast Cancer
Biological: trastuzumab
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: paclitaxel
Drug: tamoxifen citrate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Trial of Paclitaxel-Herceptin Adjuvant Therapy for Early Stage Breast Cancer

Resource links provided by NLM:


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

Enrollment: 200
Study Start Date: August 1999
Study Completion Date: March 2009
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive paclitaxel IV over 3 hours immediately followed by trastuzumab (Herceptin) IV over 30-90 minutes on day 1. Paclitaxel repeats every 3 weeks for 4 courses and trastuzumab (Herceptin) repeats weekly for 10 courses. At 3 weeks following paclitaxel and trastuzumab (Herceptin), patients receive doxorubicin IV and cyclophosphamide IV over 1 hour every 3 weeks for 4 courses. Following chemotherapy, estrogen receptor (ER) positive and/or progesterone receptor (PR) positive patients receive oral tamoxifen twice daily for 5 years.
Biological: trastuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel Drug: tamoxifen citrate
Experimental: Arm II
Patients receive same therapy as in Arm I, except for additional trastuzumab (Herceptin) IV weekly beginning within 3 weeks following completion of chemotherapy and local therapy and continuing for 1 year. ER and/or PR positive patients receive tamoxifen as in Arm I but may be concurrent with trastuzumab (Herceptin). Following completion of doxorubicin and cyclophosphamide, post lumpectomy and post mastectomy patients may receive local radiotherapy daily for 5-6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Biological: trastuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel

Detailed Description:

OBJECTIVES:

I. Evaluate the safety of paclitaxel plus trastuzumab (Herceptin) followed by adjuvant chemotherapy in women with node positive stage II or IIIa breast cancer with HER2 overexpression.

II. Evaluate the safety of long term trastuzumab (Herceptin) in this patient population.

OUTLINE: This is a randomized study. Patients are stratified according to radiotherapy (none planned vs planned to breast or chest wall). Patients are randomized to one of two treatment arms.

ARM I: Patients receive paclitaxel IV over 3 hours immediately followed by trastuzumab (Herceptin) IV over 30-90 minutes on day 1. Paclitaxel repeats every 3 weeks for 4 courses and trastuzumab (Herceptin) repeats weekly for 10 courses. At 3 weeks following paclitaxel and trastuzumab (Herceptin), patients receive doxorubicin IV and cyclophosphamide IV over 1 hour every 3 weeks for 4 courses. Following chemotherapy, estrogen receptor (ER) positive and/or progesterone receptor (PR) positive patients receive oral tamoxifen twice daily for 5 years.

ARM II: Patients receive same therapy as in Arm I, except for additional trastuzumab (Herceptin) IV weekly beginning within 3 weeks following completion of chemotherapy and local therapy and continuing for 1 year. ER and/or PR positive patients receive tamoxifen as in Arm I but may be concurrent with trastuzumab (Herceptin). Following completion of doxorubicin and cyclophosphamide, post lumpectomy and post mastectomy patients may receive local radiotherapy daily for 5-6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 200 patients (100 per treatment arm) will be accrued for this study within 1 year.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Histologically confirmed stage II or IIIa (T1-T3, N1-N2, M0) adenocarcinoma of the breast HER2 overexpression (2-3+ by immunochemistry)
  • Bilateral breast cancer allowed
  • Must have had local breast cancer surgery within past 12 weeks
  • Mastectomy or lumpectomy with clear surgical margins AND axillary lymph node dissection with at least 6 nodes removed
  • Hormone receptor status: Not specified

PATIENT CHARACTERISTICS:

  • Age: 18 and over
  • Sex: Female
  • WBC at least 3,000/mm3
  • Platelet count at least 100,000/mm3
  • Hemoglobin at least 9 g/dL
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • Creatinine no greater than 1.5 times ULN
  • LVEF at least 50%
  • No history of congestive cardiomyopathy
  • No congestive heart failure or myocardial infarction within the past 6 months
  • No uncontrolled hypertension
  • No uncontrolled arrhythmia within the past 6 months
  • No other prior malignancy within the past 5 years except curatively treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
  • No other serious medical illness that would limit survival to less than 2 years
  • No psychiatric condition precluding study
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy for breast cancer
  • No prior hormonal therapy for breast cancer
  • At least one year since prior tamoxifen for chemoprevention (e.g., Breast Cancer Prevention Trial)
  • No prior radiotherapy to the breast, chest wall, or regional lymph nodes
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003992

  Show 45 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: George W. Sledge, MD Indiana University Melvin and Bren Simon Cancer Center
  More Information

Additional Information:
Publications:
Sledge GW, O'Neill A, Thor A, et al.: Adjuvant trastuzumab: long-term results of E2198. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-2075, S106, 2006.

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003992     History of Changes
Other Study ID Numbers: NCI-2012-02305, E-2198, CDR0000067197
Study First Received: November 1, 1999
Last Updated: May 31, 2013
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Paclitaxel
Tamoxifen
Trastuzumab
Alkylating Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Bone Density Conservation Agents
Enzyme Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on November 25, 2014