Clinical trial NCT00796978: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage I breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
HER2-positive breast cancer
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2008-11-24
Enrollment: 56
Sex: FEMALE
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Percent of Participants Experiencing Cardiac Events at 1 Year
timeFrame: At 1 year
Secondary outcomes:
measure: Percent of Participants Experiencing Cardiac Events at 3 Years
timeFrame: At 3 years
measure: Percent of Participants Experiencing Cardiac Events at 5 Years
timeFrame: At 5 years
measure: Percent of Participants of Asymptomatic Left Ventricular (LV) Cardiac Dysfunction at 1 Year
timeFrame: At 1 year
measure: Percent of Participants With Asymptomatic LV Cardiac Dysfunction at Three Years
timeFrame: At 3 years
measure: Percent of Participants With Asymptomatic LV Cardiac Dysfunction at Five Years
timeFrame: At 5 years
measure: Percent of Participants With Disease-free Survival (DFS)
timeFrame: At 1 year
measure: Percent of Participants With DFS
timeFrame: At 2 years
measure: Percent of Participants With Disease-free Survival (DFS)
timeFrame: At 3 years
measure: Percent of Participants With Disease-free Survival (DFS)
timeFrame: At 5 years
measure: Overall Survival (OS) as Measured by Percent of Participants Alive at 1 Year
timeFrame: Up to 1 years
measure: Overall Survival (OS) as Measured by Percent of Participants Alive at 2 Years
timeFrame: Up to 2 years
measure: Overall Survival (OS) as Measured by Percent of Participants Alive at 3 Years
timeFrame: Up to 3 years
measure: Overall Survival (OS) as Measured by Percent of Participants Alive at 5 Years
timeFrame: Up to 5 years
measure: Mean Change in Quality of Life From Baseline to Mid-treatment
timeFrame: From Baseline to mid-treatment (week 26)
measure: Mean Change in Quality of Life From Baseline to End of Treatment
timeFrame: From baseline to end-of-treatment (52 weeks)
measure: Mean Change in Functional Status
timeFrame: From Baseline to mid-treatment (week 26)
measure: Mean Change in Functional Status
timeFrame: baseline to end-of-treatment (52 weeks)
measure: Mean Change in Cognitive Status
timeFrame: From Baseline to mid-treatment (week 26)
measure: Mean Change in Cognitive Status
timeFrame: From baseline to end-of-treatment (52 weeks)
measure: Mean Change in Psychosocial Status (Depression)
timeFrame: From Baseline to mid-treatment (week 26)
measure: Mean Change in Psychosocial Status (Depression)
timeFrame: From baseline to end-of-treatment (52 weeks)
measure: Mean Change in Psychosocial Status (Social Support)
timeFrame: From Baseline to mid-treatment (week 26)
measure: Mean Change in Psychosocial Status (Social Support)
timeFrame: From baseline to end-of-treatment (52 weeks)
measure: Mean Change in Nutritional Status
timeFrame: From Baseline to mid-treatment (week 26)
measure: Mean Change in Nutritional Status
timeFrame: From baseline to end-of-treatment (52 weeks)
measure: Mean Change in Pro-inflammatory Cytokines
timeFrame: From Baseline to mid-treatment (week 26)
measure: Mean Change in Pro-inflammatory Cytokines
timeFrame: From baseline to end-of-treatment (52 weeks)
measure: Mean Change in Plasma Cardiac Markers
timeFrame: From Baseline to mid-treatment (week 26)
measure: Mean Change in Plasma Cardiac Markers
timeFrame: From baseline to end-of-treatment (52 weeks)
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami, Sylvester Comprehensive Cancer Center
state: Florida
city: Winston-Salem
country: United States
facility: Wake Forrest
state: North Carolina
city: Cleveland
country: United States
facility: Lake/University Seidman Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: University Suburban Health Center
state: Ohio
city: Cleveland
country: United States
facility: UHHS Chagrin Highlands Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Southwest General Health Center
state: Ohio
city: Cleveland
country: United States
facility: UHHS Westlake Medical Center
state: Ohio
city: Mayfield Heights
country: United States
facility: UH-Monarch
state: Ohio
city: Wadsworth
country: United States
facility: Sharon Health Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
name: Cynthia Owusu, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: