Trastuzumab in Treating Older Women With Early-Stage Breast Cancer

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00796978
• Other study ID #: CASE10107
• Status: Completed
• Phase: Phase 2
• Start date: February 5, 2009
• Est. completion date: February 26, 2020

Study information

• Verified date: April 2024
• Source: Case Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: February 26, 2020
• Est. primary completion date: January 6, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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:
• 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-a).

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.
• 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.

Locations

Country	Name	City	State
United States	Lake/University Seidman Cancer Center	Cleveland	Ohio
United States	Southwest General Health Center	Cleveland	Ohio
United States	UHHS Chagrin Highlands Medical Center	Cleveland	Ohio
United States	UHHS Westlake Medical Center	Cleveland	Ohio
United States	University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center	Cleveland	Ohio
United States	University Suburban Health Center	Cleveland	Ohio
United States	UH-Monarch	Mayfield Heights	Ohio
United States	University of Miami, Sylvester Comprehensive Cancer Center	Miami	Florida
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Sharon Health Center	Wadsworth	Ohio
United States	Wake Forrest	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Cynthia Owusu, MD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of Participants Experiencing Cardiac Events 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.	At 1 year
Secondary	Percent of Participants Experiencing Cardiac Events 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.	At 3 years
Secondary	Percent of Participants Experiencing Cardiac Events 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.	At 5 years
Secondary	Percent of Participants of Asymptomatic Left Ventricular (LV) Cardiac Dysfunction 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	At 1 year
Secondary	Percent of Participants With Asymptomatic LV Cardiac Dysfunction at Three 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	At 3 years
Secondary	Percent of Participants With Asymptomatic LV Cardiac Dysfunction at Five Years	Five-year cumulative incidence as measured by percent of participants that had asymptomatic LV cardiac dysfunction with/without permanent discontinuation	At 5 years
Secondary	Percent of Participants With Disease-free Survival (DFS)	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.	At 1 year
Secondary	Percent of Participants With DFS	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.	At 2 years
Secondary	Percent of Participants With Disease-free Survival (DFS)	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.	At 3 years
Secondary	Percent of Participants With Disease-free Survival (DFS)	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.	At 5 years
Secondary	Overall Survival (OS) as Measured by Percent of Participants Alive at 1 Year	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.	Up to 1 years
Secondary	Overall Survival (OS) as Measured by Percent of Participants Alive at 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.	Up to 2 years
Secondary	Overall Survival (OS) as Measured by Percent of Participants Alive at 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.	Up to 3 years
Secondary	Overall Survival (OS) as Measured by Percent of Participants Alive at 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.	Up to 5 years
Secondary	Mean Change in Quality of Life From Baseline to Mid-treatment	Quality of life was assessed by using the mean change in Functional Assessment of Cancer Therapy-Breast (FACTB) scoring instrument. The Functional Assessment of Cancer Therapy-Breast (FACT-B) is a 37-item instrument designed to measure five domains of HRQOL in breast cancer patients: Physical, social, emotional, and functional well-being, as well as a breast-cancer subscale (BCS). Each question response is based on a 5-point Likert-type scale. Scores range from 0-148. High scores indicate better QOL.	From Baseline to mid-treatment (week 26)
Secondary	Mean Change in Quality of Life From Baseline to End of Treatment	Quality of life was assessed by using the mean change in Functional Assessment of Cancer Therapy-Breast (FACTB) scoring instrument. The Functional Assessment of Cancer Therapy-Breast (FACT-B) is a 37-item instrument designed to measure five domains of HRQOL in breast cancer patients: Physical, social, emotional, and functional well-being, as well as a breast-cancer subscale (BCS). Each question response is based on a 5-point Likert-type scale. Scores range from 0-148. High scores indicate better QOL.	From baseline to end-of-treatment (52 weeks)
Secondary	Mean Change in Functional Status	Mean Change in ADL/IADL scores From Baseline to Mid-treatment. The functional status will be measured by a Comprehensive Geriatric Assessment comprised of two validated instruments: Katz's Activity of Daily Living (ADL) instrument and Lawton's Instrumental of Activities of Daily Living (IADL). The IADL scale contains eight items with a summary score from 0 (low function) to 8 (high function), with higher scores indicating higher function. The ADL scale contains six items with a summary score of 0 to 6, with higher scores indicating higher independence. A score of 6 indicates complete independence; a score of 4 indicates moderate impairment; 2 or less indicates severe functional impairment. The scores of both scales will be added together for a comprehensive geriatric assessment score.	From Baseline to mid-treatment (week 26)
Secondary	Mean Change in Functional Status	Mean Change in ADL/IADL scores From Baseline to End of Treatment. The functional status will be measured by a Comprehensive Geriatric Assessment comprised of two validated instruments: Katz's Activity of Daily Living (ADL) instrument and Lawton's Instrumental of Activities of Daily Living (IADL). The IADL scale contains eight items with a summary score from 0 (low function) to 8 (high function), with higher scores indicating higher function. The ADL scale contains six items with a summary score of 0 to 6, with higher scores indicating higher independence. A score of 6 indicates complete independence; a score of 4 indicates moderate impairment; 2 or less indicates severe functional impairment. The scores of both scales will be added together for a comprehensive geriatric assessment score.	baseline to end-of-treatment (52 weeks)
Secondary	Mean Change in Cognitive Status	Mean Change in Mini Mental Status Exam (MMSE scores) From Baseline to Mid-treatment. The Mini-Mental Status Exam contains 11 items to gauge cognitive function. The minimum score is 0. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The higher the score, the better the participant's function (Scores 30-24 indicate uncertain cognitive impairment; scores 23-18 indicate mild to moderate cognitive impairment; scores 17-0 indicate severe cognitive impairment).	From Baseline to mid-treatment (week 26)
Secondary	Mean Change in Cognitive Status	Mean Change in Mini Mental Status Exam (MMSE scores) From Baseline to End of Treatment. The Mini-Mental Status Exam contains 11 items to gauge cognitive function. The minimum score is 0. The maximum score is 30. A score of 23 or lower is indicative of cognitive impairment. The higher the score, the better the participant's function (Scores 30-24 indicate uncertain cognitive impairment; scores 23-18 indicate mild to moderate cognitive impairment; scores 17-0 indicate severe cognitive impairment).	From baseline to end-of-treatment (52 weeks)
Secondary	Mean Change in Psychosocial Status (Depression)	Mean Change in Geriatric Depression Scores From Baseline to Mid-treatment. The Geriatric Depression Scale (GDS) is a validated tool with 15 items. The minimum score is 0, and the maximum is 15. Scores of 0-4 are considered normal, depending on age, education, and complaints; 5-8 indicate mild depression; 9-11 indicate moderate depression; and 12-15 indicate severe depression.	From Baseline to mid-treatment (week 26)
Secondary	Mean Change in Psychosocial Status (Depression)	Mean Change in Geriatric Depression Scores from Baseline to End of Treatment. The Geriatric Depression Scale (GDS) is a validated tool with 15 items. The minimum score is 0, and the maximum is 15. Scores of 0-4 are considered normal, depending on age, education, and complaints; 5-8 indicate mild depression; 9-11 indicate moderate depression; and 12-15 indicate severe depression.	From baseline to end-of-treatment (52 weeks)
Secondary	Mean Change in Psychosocial Status (Social Support)	Mean Change in MOS social support scores From Baseline to Mid-treatment. The Medical Outcomes Study (MOS) Social Support survey tool measures multiple domains. It is a 19-item tool comprised of four subscales in one overall summary index. The subscales are Emotional/Informational Support, Tangible Support, Affectionate support, and Positive Social Interaction. The overall index score is determined by calculating the mean of all 19 items. Scores range from 19 to 95, with higher scores indicating high support availability to participants.	From Baseline to mid-treatment (week 26)
Secondary	Mean Change in Psychosocial Status (Social Support)	Mean Change in MOS social support scores From Baseline to End of Treatment. The Medical Outcomes Study (MOS) Social Support survey tool measures multiple domains. It is a 19-item tool comprised of four subscales in one overall summary index. The subscales are Emotional/Informational Support, Tangible Support, Affectionate support, and Positive Social Interaction. The overall index score is determined by calculating the mean of all 19 items. Scores range from 19 to 95, with higher scores indicating high support availability to participants.	From baseline to end-of-treatment (52 weeks)
Secondary	Mean Change in Nutritional Status	Mean Change in Mini Nutrition Assessment scores From Baseline to Mid-treatment. The Mini Nutritional Screening is a scale comprised of six questions. The sum of the six questions is totaled to determine a score which is designed to assess if there is a risk of malnutrition. The highest score possible, 14, indicated no risk, and the minimum score of 0 indicates the highest risk possible. 12 points or greater is considered no risk or normal. Meanwhile, a score below 11 indicates possible malnutrition.	From Baseline to mid-treatment (week 26)
Secondary	Mean Change in Nutritional Status	Mean Change in Mini Nutrition Assessment scores From Baseline to End of Treatment. The Mini Nutritional Screening is a scale comprised of six questions. The sum of the six questions is totaled to determine a score which is designed to assess if there is a risk of malnutrition. The highest score possible, 14, indicated no risk, and the minimum score of 0 indicates the highest risk possible. 12 points or greater is considered no risk or normal. Meanwhile, a score below 11 indicates possible malnutrition.	From baseline to end-of-treatment (52 weeks)
Secondary	Mean Change in Pro-inflammatory Cytokines	Mean change in pro-inflammatory cytokines from baseline to mid-treatment	From Baseline to mid-treatment (week 26)
Secondary	Mean Change in Pro-inflammatory Cytokines	Mean change in pro-inflammatory cytokines from baseline to end of treatment	From baseline to end-of-treatment (52 weeks)
Secondary	Mean Change in Plasma Cardiac Markers	Mean change in plasma cardiac markers from baseline to mid-treatment	From Baseline to mid-treatment (week 26)
Secondary	Mean Change in Plasma Cardiac Markers	Mean change in plasma cardiac markers from baseline end of treatment	From baseline to end-of-treatment (52 weeks)