Trastuzumab in Treating Older Women With Early-Stage Breast Cancer

• ClinicalTrials.gov Identifier: NCT00796978
• Recruitment Status: Completed
• First Posted: November 24, 2008
• Results First Posted: August 3, 2020
• Last Update Posted: August 3, 2020
• Sponsor: Cynthia Owusu, MD
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Cynthia Owusu, MD, Case Comprehensive Cancer Center

Tracking Information

• First Submitted Date: November 21, 2008
• First Posted Date: November 24, 2008
• Results First Submitted Date: April 21, 2020
• Results First Posted Date: August 3, 2020
• Last Update Posted Date: August 3, 2020
• Actual Study Start Date: November 11, 2008
• Actual Primary Completion Date: January 12, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 16, 2020)

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.

• Original Primary Outcome Measures (submitted: November 21, 2008): Three-year cumulative incidence of cardiac events

Current Secondary Outcome Measures (submitted: July 16, 2020)

• 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.
• 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.
• 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
• 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
• 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
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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 ]

Original Secondary Outcome Measures (submitted: November 21, 2008)

• Three-year cumulative incidence of asymptomatic left ventricular cardiac dysfunction
• Mean change in plasma cardiac markers from baseline to mid-treatment and baseline to end of treatment
• Mean change in pro-inflammatory cytokines from baseline to mid-treatment and baseline to end of treatment
• Mean change in quality of life and comprehensive geriatric assessment scores from baseline to mid-treatment and baseline to end of treatment
• Disease-free survival
• Overall survival

Current Other Pre-specified Outcome Measures (submitted: July 16, 2020)

• 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 ]
• 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 ]

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trastuzumab in Treating Older Women With Early-Stage Breast Cancer
• 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

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.

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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Breast Cancer

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 Name: 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.

Study Arms

Experimental: trastuzumab

Interventions:

• Biological: trastuzumab
• Other: laboratory biomarker analysis
• Procedure: adjuvant therapy
• Procedure: quality-of-life assessment

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 13, 2015): 56
• Original Estimated Enrollment (submitted: November 21, 2008): 124
• Actual Study Completion Date: January 12, 2019
• Actual Primary Completion Date: January 12, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 60 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00796978
• Other Study ID Numbers: CASE10107; P30CA043703 ( U.S. NIH Grant/Contract ); CASE10107 ( Other Identifier: Case Comprehensive Cancer Center ); CASE-10107-CC443 ( Other Identifier: Cancer Center IRB )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Cynthia Owusu, MD, Case Comprehensive Cancer Center
• Original Responsible Party: Cynthia Owusu, Case Comprehensive Cancer Center
• Current Study Sponsor: Cynthia Owusu, MD
• Original Study Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)

Investigators

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

• PRS Account: Case Comprehensive Cancer Center
• Verification Date: July 2020