Trastuzumab With or Without Tamoxifen in Treating Women With Progressive Stage IV Breast Cancer

This study has been withdrawn prior to enrollment.
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: January 27, 2003
Last updated: January 11, 2007
Last verified: December 2006

RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using tamoxifen may fight breast cancer by blocking the uptake of estrogen. Combining trastuzumab with tamoxifen may kill more tumor cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of trastuzumab with or without trastuzumab in treating women who have invasive stage IV breast cancer.

Condition Intervention Phase
Stage IV Breast Cancer
Recurrent Breast Cancer
Drug: tamoxifen
Drug: trastuzumab
Procedure: antibody therapy
Procedure: antiestrogen therapy
Procedure: biological response modifier therapy
Procedure: drug resistance inhibition
Procedure: endocrine therapy
Procedure: hormone therapy
Procedure: monoclonal antibody therapy
Phase 3

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase III Randomized Study of Trastuzumab (Herceptin) With or Without Tamoxifen in Women With Progressive, Stage IV, Estrogen or Progesterone Receptor- and HER2/Neu-Positive Breast Cancer

Resource links provided by NLM:

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

Detailed Description:


  • Compare time to progression in women with progressive, stage IV, estrogen or progesterone receptor- and HER2/neu-positive breast cancer treated with trastuzumab (Herceptin) with or without tamoxifen.
  • Correlate response with type of measurement (immunohistochemistry or fluorescent in situ hybridization) of HER2/neu expression in patients treated with these regimens.
  • Compare objective response rate (complete or partial response) in patients treated with these regimens.

OUTLINE: This is a randomized study. Patients are stratified according to prior adjuvant treatment (yes vs no), ECOG performance status (0-1 vs 2), and prior aromatase inhibitor treatment (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive trastuzumab (Herceptin) IV over 60-90 minutes on day 1.
  • Arm II: Patients receive trastuzumab as in arm I and oral tamoxifen once daily on days 1-21.

In both arms, treatment repeats every 3 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 280 patients (140 per treatment arm) will be accrued for this study within 28 months.


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


  • Histologically confirmed invasive stage IV breast cancer
  • Hormone receptor status:
  • HER2/neu positive (3+ by immunohistochemical [IHC] assay or fluorescent in situ hybridization [FISH])
  • Estrogen receptor or progesterone receptor positive
  • Measurable or evaluable disease
  • Must have disease progression within 6 months of initiation of tamoxifen (administered in the adjuvant or metastatic setting) or during aromatase inhibitor therapy



  • 18 and over


  • Female

Menopausal status

  • Not specified

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • Absolute neutrophil count at least 1,000/mm^3
  • Platelet count at least 75,000/mm^3


  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • SGOT and SGPT no greater than 2.5 times ULN


  • Not specified


  • LVEF normal by MUGA


  • Not pregnant or nursing
  • Fertile patients must use effective nonhormonal contraception during and for at least 2 months after study completion
  • No other concurrent active malignancy except nonmelanoma skin cancer
  • Patients who have completed prior therapy and are at less than 30% risk of relapse are not considered to have an active malignancy


Biologic therapy

  • No prior trastuzumab (Herceptin) in the adjuvant or metastatic setting


  • No more than 1 prior chemotherapy regimen in the metastatic setting
  • No concurrent chemotherapy

Endocrine therapy

  • See Disease Characteristics
  • No more than 1 prior hormonal therapy regimen for metastatic disease
  • Prior aromatase inhibitor therapy administered in the first-line metastatic or adjuvant setting is allowed provided there is disease progression on tamoxifen
  • No other concurrent hormonal therapy except the following:
  • Steroids for adrenal failure
  • Hormones for nondisease-related conditions (e.g., insulin for diabetes)
  • Intermittent use of dexamethasone as an antiemetic
  • Vaginal estrogen (or Estring®) for vaginal dryness


  • No concurrent palliative radiotherapy except whole brain irradiation for CNS disease


  • Not specified


  • Concurrent bisphosphonates allowed
  • No concurrent cardioprotective drugs
  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 identifier: NCT00053339

Sponsors and Collaborators
Cancer and Leukemia Group B
Study Chair: Joanne E. Mortimer, MD Sentara Cancer Center
  More Information

No publications provided Identifier: NCT00053339     History of Changes
Other Study ID Numbers: CDR0000269409, CLB-49903
Study First Received: January 27, 2003
Last Updated: January 11, 2007
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Bone Density Conservation Agents
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Selective Estrogen Receptor Modulators
Therapeutic Uses processed this record on July 01, 2015