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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Stage IV Breast Cancer; Recurrent Breast Cancer
• Intervention / Treatment: Drug: trastuzumab; Drug: tamoxifen

Detailed Description

OBJECTIVES:

• 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.

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Sex

• Female

Performance status

• ECOG 0-2

Hematopoietic

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

Hepatic

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

Cardiovascular

• LVEF normal by MUGA

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

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

Chemotherapy

• 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

Radiotherapy

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

Other

• Concurrent bisphosphonates allowed
• No concurrent cardioprotective drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: trastuzumab; Patients receive trastuzumab (Herceptin) IV over 60-90 minutes on day 1. 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.	Drug: trastuzumab
Experimental: trastuzumab + tamoxifen; Patients receive trastuzumab V over 60-90 minutes on day 1 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.	Drug: trastuzumab; Drug: tamoxifen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to progression	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
response	Up to 5 years
response rate	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Joanne E. Mortimer, MD, Sentara Cancer Center

Study record dates

Study Major Dates

• Study Start: December 7, 2022
• Primary Completion: December 7, 2022
• Study Completion: December 7, 2022

Study Registration Dates

• First Submitted: January 27, 2003
• First Submitted That Met QC Criteria: January 27, 2003
• First Posted (Estimate): January 28, 2003

Study Record Updates

• Last Update Posted (Estimate): July 12, 2016
• Last Update Submitted That Met QC Criteria: July 11, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Trastuzumab; Tamoxifen
• Other Study ID Numbers: CALGB-49903; CDR0000269409 (Registry Identifier: PDQ (Physician Data Query))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No