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Completed

NCT Number: NCT00796978

Trastuzumab in Treating Older Women With Early-Stage Breast Cancer

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.

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Key information

Conditions

Breast Cancer Breast Diseases Breast Neoplasms Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

60 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

University of Miami, Sylvester Comprehensive Cancer Center, Miami, Florida, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

trastuzumab

Biological

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

laboratory biomarker analysis

Other

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

Procedure

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

Procedure

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.

Primary outcomes

  1. Percent of Participants Experiencing Cardiac Events at 1 Year

    Time frame: 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 outcomes

  1. Percent of Participants Experiencing Cardiac Events at 3 Years

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: 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

    Time frame: 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)

    Time frame: 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)

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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 From Baseline to Mid-treatment

    Time frame: From Baseline to mid-treatment (week 26)

    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.

  15. Mean Change in Quality of Life From Baseline to End of Treatment

    Time frame: From baseline to end-of-treatment (52 weeks)

    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.

  16. Mean Change in Functional Status

    Time frame: From Baseline to mid-treatment (week 26)

    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.

  17. Mean Change in Functional Status

    Time frame: baseline to end-of-treatment (52 weeks)

    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.

  18. Mean Change in Cognitive Status

    Time frame: From Baseline to mid-treatment (week 26)

    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).

  19. Mean Change in Cognitive Status

    Time frame: From baseline to end-of-treatment (52 weeks)

    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).

  20. Mean Change in Psychosocial Status (Depression)

    Time frame: From Baseline to mid-treatment (week 26)

    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.

  21. Mean Change in Psychosocial Status (Depression)

    Time frame: From baseline to end-of-treatment (52 weeks)

    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.

  22. Mean Change in Psychosocial Status (Social Support)

    Time frame: From Baseline to mid-treatment (week 26)

    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.

  23. Mean Change in Psychosocial Status (Social Support)

    Time frame: From baseline to end-of-treatment (52 weeks)

    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.

  24. Mean Change in Nutritional Status

    Time frame: From Baseline to mid-treatment (week 26)

    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.

  25. Mean Change in Nutritional Status

    Time frame: From baseline to end-of-treatment (52 weeks)

    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.

  26. Mean Change in Pro-inflammatory Cytokines

    Time frame: From Baseline to mid-treatment (week 26)

    Mean change in pro-inflammatory cytokines from baseline to mid-treatment

  27. Mean Change in Pro-inflammatory Cytokines

    Time frame: From baseline to end-of-treatment (52 weeks)

    Mean change in pro-inflammatory cytokines from baseline to end of treatment

  28. Mean Change in Plasma Cardiac Markers

    Time frame: From Baseline to mid-treatment (week 26)

    Mean change in plasma cardiac markers from baseline to mid-treatment

  29. Mean Change in Plasma Cardiac Markers

    Time frame: From baseline to end-of-treatment (52 weeks)

    Mean change in plasma cardiac markers from baseline end of treatment

Sponsors and collaborators

Lead sponsor

Cynthia Owusu, MD

Other

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2016
Study completion
2020
First posted
Nov 24, 2008
Registry last updated
May 1, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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