Trastuzumab in Treating Older Women With Early-Stage Breast Cancer

• Sponsor: Cynthia Owusu, MD (Other)
• Overall Status: Completed
• CT.gov ID: NCT00796978
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 56
• Locations: 11
• Arm: 1
• Actual Duration (Months): 122
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.

PURPOSE: This phase II trial is studying the side effects of trastuzumab and to see how well it works in treating older women with early-stage breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: trastuzumab; Other: laboratory biomarker analysis; Procedure: adjuvant therapy; Procedure: quality-of-life assessment	Phase 2

Detailed Description

OBJECTIVES:

Primary

• To evaluate the 3-year cumulative incidence of cardiac events in women 60 years and older with HER2-positive breast cancer who receive single agent trastuzumab (Herceptin®) in the adjuvant setting.

Secondary

• To evaluate the 1-year cumulative incidence of asymptomatic cardiac left ventricular dysfunction in women 60 years and older with Her2-positive breast cancer who receive single agent trastuzumab in the adjuvant setting.

• To evaluate long-term cardiac toxicity (5-year cumulative incidence of cardiac events) in women 60 years and older with Her2-positive breast cancer who receive single agent trastuzumab in the adjuvant setting.

• To assess the relation between physiologic markers of chronic heart failure and trastuzumab-related cardiac dysfunction in women 60 years and older with Her2-positive breast cancer who receive single agent trastuzumab.

• To assess the relation between pro-inflammatory cytokines and trastuzumab-related cardiac dysfunction in women 60 years and older with Her2-positive breast cancer.

• To determine the effect of this drug on the health-related quality of life and functional, cognitive, and mental status of women 60 years and older with Her2-positive breast cancer.

• To determine the 5-year disease-free survival and overall survival of women 60 years and older with Her2-positive breast cancer who receive single agent trastuzumab in the adjuvant setting.

OUTLINE: This is a multicenter study.

Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity.

Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.

After completion of study therapy, patients are followed periodically for 4 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 56 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Single Agent Adjuvant Trastuzumab (Herceptin®) in Older Women With Early-Stage and Locally Advanced Breast Cancer: A Phase II Trial
• Actual Study Start Date: Nov 11, 2008
• Actual Primary Completion Date: Jan 12, 2018
• Actual Study Completion Date: Jan 12, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: trastuzumab

Biological: trastuzumab; Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity.; Other Names: Herceptin ; Other: laboratory biomarker analysis; Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α).; Procedure: adjuvant therapy; Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity.; Procedure: quality-of-life assessment; Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.

Outcome Measures

Primary Outcome Measures

1. Percent of Participants Experiencing Cardiac Events at 1 Year [At 1 year]

   Number of participants that experience cardiac events that include cardiac death due to congestive heart failure (CHF), Myocardial infarction (MI) or documented arrhythmia, death without definitive cause, or signs and symptoms of CHF as defined by New York Heart Association (NYHA) class III or IV symptoms.

Secondary Outcome Measures

1. Percent of Participants Experiencing Cardiac Events at 3 Years [At 3 years]

   Number of participants that experience cardiac events that include cardiac death due to congestive heart failure (CHF), Myocardial infarction (MI) or documented arrhythmia, death without definitive cause, or signs and symptoms of CHF as defined by New York Heart Association (NYHA) class III or IV symptoms.

2. Percent of Participants Experiencing Cardiac Events at 5 Years [At 5 years]

   Number of participants that experience cardiac events that include cardiac death due to congestive heart failure (CHF), Myocardial infarction (MI) or documented arrhythmia, death without definitive cause, or signs and symptoms of CHF as defined by New York Heart Association (NYHA) class III or IV symptoms.

3. Percent of Participants of Asymptomatic Left Ventricular (LV) Cardiac Dysfunction at 1 Year [At 1 year]

   One-year cumulative incidence of LV cardiac dysfunction as measured by percent of participants that had asymptomatic LV cardiac dysfunction with/without permanent discontinuation

4. Percent of Participants With Asymptomatic LV Cardiac Dysfunction at Three Years [At 3 years]

   Three-year cumulative incidence of LV cardiac dysfunction as measured by percent of participants that had asymptomatic LV cardiac dysfunction with/without permanent discontinuation

5. Percent of Participants With Asymptomatic LV Cardiac Dysfunction at Five Years [At 5 years]

   Five-year cumulative incidence as measured by percent of participants that had asymptomatic LV cardiac dysfunction with/without permanent discontinuation

6. Percent of Participants With Disease-free Survival (DFS) [At 1 year]

   Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.

7. Percent of Participants With DFS [At 2 years]

   Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.

8. Percent of Participants With Disease-free Survival (DFS) [At 3 years]

   Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.

9. Percent of Participants With Disease-free Survival (DFS) [At 5 years]

   Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.

10. Overall Survival (OS) as Measured by Percent of Participants Alive at 1 Year [Up to 1 years]

    OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.

11. Overall Survival (OS) as Measured by Percent of Participants Alive at 2 Years [Up to 2 years]

    OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.

12. Overall Survival (OS) as Measured by Percent of Participants Alive at 3 Years [Up to 3 years]

    OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.

13. Overall Survival (OS) as Measured by Percent of Participants Alive at 5 Years [Up to 5 years]

    OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.

14. Mean Change in Quality of Life and Comprehensive Geriatric Assessment Scores From Baseline to Mid-treatment and Baseline to End of Treatment [Baseline to week 26 and baseline to 52 weeks after being on study]

Other Outcome Measures

1. Mean Change in Pro-inflammatory Cytokines From Baseline to Mid-treatment and Baseline to End of Treatment [Every 6 weeks during treatment up to three years]

2. Mean Change in Plasma Cardiac Markers From Baseline to Mid-treatment and Baseline to End of Treatment [Every 6 weeks during treatment up to three years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the breast

• Immunohistochemical staining for Her2 protein of 3+ intensity or Her2 gene amplification of ≥ 2.0 by FISH testing.

• Life expectancy > 6 months

• ECOG performance status ≤ 2

• Node positive disease irrespective of tumor size

• Node negative disease:

• TNM Stage (AJCC Cancer Staging Manual 6th edition) T1b-T4, N0-3, M0, irrespective of hormonal status

• Baseline LVEF ≥ lower limit of normal for a particular institution

• Complete surgical removal of invasive cancer by mastectomy or lumpectomy

• Complete staging work-up with CT of chest, abdomen, and pelvis plus bone scan or alternatively with PET scan for stage II and higher disease, or as determined by symptoms for all other stages. Additional staging work-up as per symptoms.

• Adequate bone marrow function as indicated by the following:

• ANC >1000/µL

• Platelets ≥100,000/µL

• Hemoglobin >10 g/dL

• Adequate liver function, as indicated by bilirubin ≤1.5 x upper limit of normal (ULN) Adequate renal function, as indicated by creatinine ≤1.5 x ULN

• AST or ALT <2 x ULN unless related to primary disease.

• Signed informed consent

Exclusion Criteria:

• Enrollment after more than 120 days from the last day of mastectomy or lumpectomy

• Patients able to tolerate and willing to receive chemotherapy

• Prior chemotherapy for current malignancy

• Prior herceptin therapy

• Active cardiac disease

• Myocardial infarction (asymptomatic changes on EKG suggestive of old MI is not an exclusion)

• Angina pectoris requiring anti-anginal treatment

• Documented congestive heart failure (CHF)

• Current use of any therapy specifically for CHF

• Cardiac arrhythmia requiring medication

• Current uncontrolled hypertension (diastolic >100 mmHg or systolic > 200 mmHg)

• Clinically significant valvular abnormality (associated with New York Heart Association (NYHA) class II, III, or IV symptoms)

• Clinically significant pericardial effusion (associated with New York Heart Association (NYHA) class II, III, or IV symptoms)

• Past cardiac disease

• Prior myocardial infarction (asymptomatic changes on EKG suggestive of old MI is not an exclusion)

• Prior history of CHF

• History of cardiomyopathy

• Other diseases and conditions

• Evidence of metastatic breast cancer (clinical or radiological evidence)

• Active infection

• Concomitant malignancies or previous malignancies within the last 3 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix.

• Hypersensitivity to trastuzumab

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Miami, Sylvester Comprehensive Cancer Center	Miami	Florida	United States	33136
2	Wake Forrest	Winston-Salem	North Carolina	United States	27157
3	Lake/University Seidman Cancer Center	Cleveland	Ohio	United States	44060
4	Cleveland Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106-5065
5	University Suburban Health Center	Cleveland	Ohio	United States	44121
6	UHHS Chagrin Highlands Medical Center	Cleveland	Ohio	United States	44122
7	Southwest General Health Center	Cleveland	Ohio	United States	44130
8	UHHS Westlake Medical Center	Cleveland	Ohio	United States	44145
9	UH-Monarch	Mayfield Heights	Ohio	United States	44124
10	Sharon Health Center	Wadsworth	Ohio	United States	44281
11	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15232

Sponsors and Collaborators

• Cynthia Owusu, MD
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Cynthia Owusu, MD, MSc, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 28, 2018
• Informed Consent Form - Nov 17, 2019

More Information

Publications

None provided.

• Responsible Party: Cynthia Owusu, MD, Principal Investigator, Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT00796978
• Other Study ID Numbers: CASE10107; P30CA043703; CASE10107; CASE-10107-CC443
• First Posted: Nov 24, 2008
• Last Update Posted: Aug 3, 2020
• Last Verified: Jul 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Cynthia Owusu, MD, Principal Investigator, Case Comprehensive Cancer Center: stage I breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; HER2-positive breast cancer
• Additional relevant MeSH terms: Breast Neoplasms; Trastuzumab

Study Results

Participant Flow

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Period Title: Overall Study
STARTED	56
COMPLETED	44
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Overall Participants	56
Age, Customized (Count of Participants)
60-69	19 33.9%
70-79	23 41.1%
80-89	13 23.2%
90-99	1 1.8%
Sex: Female, Male (Count of Participants)
Female	56 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 1.8%
Not Hispanic or Latino	55 98.2%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 12.5%
White	49 87.5%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	56 100%

Outcome Measures

1. Primary Outcome

Title	Percent of Participants Experiencing Cardiac Events at 1 Year
Description	Number of participants that experience cardiac events that include cardiac death due to congestive heart failure (CHF), Myocardial infarction (MI) or documented arrhythmia, death without definitive cause, or signs and symptoms of CHF as defined by New York Heart Association (NYHA) class III or IV symptoms.
Time Frame	At 1 year

Outcome Measure Data

Analysis Population Description

All subjects that received treatment. All related outcomes occurred within 1 year, therefore, 3-year and 5-year cumulative incidences of cardiac events and asymptomatic LV cardiac dysfunction were not performed.

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	55
Number (95% Confidence Interval) [percentage of participants]	3.6 6.4%

2. Secondary Outcome

Title	Percent of Participants Experiencing Cardiac Events at 3 Years
Description	Number of participants that experience cardiac events that include cardiac death due to congestive heart failure (CHF), Myocardial infarction (MI) or documented arrhythmia, death without definitive cause, or signs and symptoms of CHF as defined by New York Heart Association (NYHA) class III or IV symptoms.
Time Frame	At 3 years

Outcome Measure Data

Analysis Population Description

Data from 3-year and 5-year echocardiograms not collected, CI of cardiac events and asymptomatic LV cardiac dysfunction were not available

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	0

3. Secondary Outcome

Title	Percent of Participants Experiencing Cardiac Events at 5 Years
Description	Number of participants that experience cardiac events that include cardiac death due to congestive heart failure (CHF), Myocardial infarction (MI) or documented arrhythmia, death without definitive cause, or signs and symptoms of CHF as defined by New York Heart Association (NYHA) class III or IV symptoms.
Time Frame	At 5 years

Outcome Measure Data

Analysis Population Description

Data from 3-year and 5-year echocardiograms not collected, CI of cardiac events and asymptomatic LV cardiac dysfunction were not available

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	0

4. Secondary Outcome

Title	Percent of Participants of Asymptomatic Left Ventricular (LV) Cardiac Dysfunction at 1 Year
Description	One-year cumulative incidence of LV cardiac dysfunction as measured by percent of participants that had asymptomatic LV cardiac dysfunction with/without permanent discontinuation
Time Frame	At 1 year

Outcome Measure Data

Analysis Population Description

All subjects that received treatment. All related outcomes occurred within 1 year, therefore, 3-year and 5-year cumulative incidences of cardiac events and asymptomatic LV cardiac dysfunction were not performed.

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	55
Number (95% Confidence Interval) [percent of participants]	9.1 16.3%

5. Secondary Outcome

Title	Percent of Participants With Asymptomatic LV Cardiac Dysfunction at Three Years
Description	Three-year cumulative incidence of LV cardiac dysfunction as measured by percent of participants that had asymptomatic LV cardiac dysfunction with/without permanent discontinuation
Time Frame	At 3 years

Outcome Measure Data

Analysis Population Description

Data from 3-year and 5-year echocardiograms not collected, CI of cardiac events and asymptomatic LV cardiac dysfunction were not available

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	0

6. Secondary Outcome

Title	Percent of Participants With Asymptomatic LV Cardiac Dysfunction at Five Years
Description	Five-year cumulative incidence as measured by percent of participants that had asymptomatic LV cardiac dysfunction with/without permanent discontinuation
Time Frame	At 5 years

Outcome Measure Data

Analysis Population Description

Data from 3-year and 5-year echocardiograms not collected, CI of cardiac events and asymptomatic LV cardiac dysfunction were not available

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	0

7. Secondary Outcome

Title	Percent of Participants With Disease-free Survival (DFS)
Description	Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.
Time Frame	At 1 year

Outcome Measure Data

Analysis Population Description

All participants that received treatment.

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	55
Number (95% Confidence Interval) [Percent of participants]	96.36 172.1%

8. Secondary Outcome

Title	Percent of Participants With DFS
Description	Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.
Time Frame	At 2 years

Outcome Measure Data

Analysis Population Description

All participants that received treatment.

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	55
Number (95% Confidence Interval) [percentage of participants]	94.47 168.7%

9. Secondary Outcome

Title	Percent of Participants With Disease-free Survival (DFS)
Description	Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.
Time Frame	At 3 years

Outcome Measure Data

Analysis Population Description

All participants that received treatment.

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	55
Number (95% Confidence Interval) [percentage of participants]	92.46 165.1%

10. Secondary Outcome

Title	Percent of Participants With Disease-free Survival (DFS)
Description	Percent of participants with DFS measured between the time from initiation of treatment to the date of first loco-regional or distant treatment failure, ignoring any intervening contralateral breast cancers or other second primary cancers. Deaths without evidence of recurrence will be treated censoring events.
Time Frame	At 5 years

Outcome Measure Data

Analysis Population Description

All participants that received treatment.

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	55
Number (95% Confidence Interval) [percentage of participants]	86.4 154.3%

11. Secondary Outcome

Title	Overall Survival (OS) as Measured by Percent of Participants Alive at 1 Year
Description	OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.
Time Frame	Up to 1 years

Outcome Measure Data

Analysis Population Description

All participants that received treatment.

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	55
Number (95% Confidence Interval) [percent of participants]	100.0 178.6%

12. Secondary Outcome

Title	Overall Survival (OS) as Measured by Percent of Participants Alive at 2 Years
Description	OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

All participants that received treatment.

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	55
Number (95% Confidence Interval) [percent of participants]	100.0 178.6%

13. Secondary Outcome

Title	Overall Survival (OS) as Measured by Percent of Participants Alive at 3 Years
Description	OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

All participants that received treatment.

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	55
Number (95% Confidence Interval) [percent of participants]	94.23 168.3%

14. Secondary Outcome

Title	Overall Survival (OS) as Measured by Percent of Participants Alive at 5 Years
Description	OS defined as percent of participants alive between time from initiation of treatment to the date of protocol-defined outcome from any cause and censored to the date of last follow-up for survivors.
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

All participants that received treatment.

Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
Measure Participants	55
Number (95% Confidence Interval) [percent of participants]	90.2 161.1%

15. Secondary Outcome

Title	Mean Change in Quality of Life and Comprehensive Geriatric Assessment Scores From Baseline to Mid-treatment and Baseline to End of Treatment
Time Frame	Baseline to week 26 and baseline to 52 weeks after being on study

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

16. Other Pre-specified Outcome

Title	Mean Change in Pro-inflammatory Cytokines From Baseline to Mid-treatment and Baseline to End of Treatment
Time Frame	Every 6 weeks during treatment up to three years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Other Pre-specified Outcome

Title	Mean Change in Plasma Cardiac Markers From Baseline to Mid-treatment and Baseline to End of Treatment
Time Frame	Every 6 weeks during treatment up to three years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse Event Data was collected up to 5 years of study participation.
Arm/Group Title	Trastuzumab
Arm/Group Description	trastuzumab: Trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. laboratory biomarker analysis: Blood is collected every 6 weeks during treatment. Samples are assessed for plasma cardiac markers (N-terminal brain natriuretic protein and troponin-I) and pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α). adjuvant therapy: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 52 weeks in the absence of disease progression or unacceptable toxicity. quality-of-life assessment: Patients complete Quality of Life and Quality of Health and Comprehensive Geriatric assessments of functional, cognitive, and mental status changes at baseline, weeks 26, and 52.
All Cause Mortality
	Trastuzumab
	Affected / at Risk (%)	# Events
Total	5/56 (8.9%)
Serious Adverse Events
	Trastuzumab
	Affected / at Risk (%)	# Events
Total	8/56 (14.3%)
Blood and lymphatic system disorders
Platelets	1/56 (1.8%)	1
Cardiac disorders
Heart failure	1/56 (1.8%)	3
Left ventricular systolic dysfunction	1/56 (1.8%)	1
Gastrointestinal disorders
Dehydration	1/56 (1.8%)	1
Diarrhea	1/56 (1.8%)	1
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Bladder (urinary)	1/56 (1.8%)	1
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)	1/56 (1.8%)	2
Musculoskeletal and connective tissue disorders
Fracture	2/56 (3.6%)	2
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/56 (1.8%)	1
Hypoxia	1/56 (1.8%)	1
Pulmonary/Upper Respiratory - Other (Specify, _Flu_)	1/56 (1.8%)	1
Vascular disorders
Thrombosis/thrombus/embolism	1/56 (1.8%)	1
Other (Not Including Serious) Adverse Events
	Trastuzumab
	Affected / at Risk (%)	# Events
Total	17/56 (30.4%)
Blood and lymphatic system disorders
Lymphopenia	2/56 (3.6%)	3
Cardiac disorders
Hypertension	6/56 (10.7%)	7
Left ventricular systolic dysfunction	2/56 (3.6%)	2
Gastrointestinal disorders
Diarrhea	2/56 (3.6%)	2
General disorders
Pain-Kidney	1/56 (1.8%)	1
Infections and infestations
Infection with unknown ANC - Urinary tract NOS	1/56 (1.8%)	1
Metabolism and nutrition disorders
Glomerular filtration rate	1/56 (1.8%)	2
Glucose, serum-low (hypoglycemia)	1/56 (1.8%)	1
Sodium, serum-low (hyponatremia)	1/56 (1.8%)	2
Musculoskeletal and connective tissue disorders
Left ankle sprain	1/56 (1.8%)	1
Pain- Buttock	1/56 (1.8%)	1
Nervous system disorders
CNS cerebrovascular ischemia	1/56 (1.8%)	1
Confusion	1/56 (1.8%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)	1/56 (1.8%)	2
Hypoxia	1/56 (1.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.