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

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 (Clinical Trial)
• 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: November 11, 2008
• Actual Primary Completion Date: January 12, 2018
• Actual Study Completion Date: January 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 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.

Outcome Measures

Primary Outcome Measures :

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 Outcome Measures :

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 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 ]

Other Outcome Measures:

1. 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 ]
2. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Florida

University of Miami, Sylvester Comprehensive Cancer Center

Miami, Florida, United States, 33136

United States, North Carolina

Wake Forrest

Winston-Salem, North Carolina, United States, 27157

United States, Ohio

Lake/University Seidman Cancer Center

Cleveland, Ohio, United States, 44060

Cleveland Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States, 44106-5065

University Suburban Health Center

Cleveland, Ohio, United States, 44121

UHHS Chagrin Highlands Medical Center

Cleveland, Ohio, United States, 44122

Southwest General Health Center

Cleveland, Ohio, United States, 44130

UHHS Westlake Medical Center

Cleveland, Ohio, United States, 44145

UH-Monarch

Mayfield Heights, Ohio, United States, 44124

Sharon Health Center

Wadsworth, Ohio, United States, 44281

United States, Pennsylvania

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)

Documents provided by Cynthia Owusu, MD, Case Comprehensive Cancer Center:

Study Protocol and Statistical Analysis Plan  [PDF] December 28, 2018

Informed Consent Form  [PDF] November 17, 2019

More Information

• Responsible Party: Cynthia Owusu, MD, Principal Investigator, Case Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: 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 )
• First Posted: November 24, 2008
• Results First Posted: August 3, 2020
• Last Update Posted: August 3, 2020
• Last Verified: July 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, 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; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Trastuzumab; Antineoplastic Agents, Immunological; Antineoplastic Agents