Trastuzumab Emtansine in Treating Older Patients With Human Epidermal Growth Factor Receptor 2-Positive Stage I-III Breast Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02414646|
Recruitment Status : Active, not recruiting
First Posted : April 13, 2015
Last Update Posted : December 14, 2018
|Condition or disease||Intervention/treatment||Phase|
|Estrogen Receptor Status HER2 Positive Breast Carcinoma Progesterone Receptor Status Stage I Breast Cancer AJCC v7 Stage IA Breast Cancer AJCC v7 Stage IB Breast Cancer AJCC v7 Stage II Breast Cancer AJCC v6 and v7 Stage IIA Breast Cancer AJCC v6 and v7 Stage IIB Breast Cancer AJCC v6 and v7 Stage III Breast Cancer AJCC v7 Stage IIIA Breast Cancer AJCC v7 Stage IIIB Breast Cancer AJCC v7 Stage IIIC Breast Cancer AJCC v7||Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Other: Questionnaire Administration Biological: Trastuzumab Emtansine||Phase 2|
I. Invasive disease-free survival (IDFS), defined as occurrence of any of the following: ipsilateral invasive breast cancer recurrence, regional invasive breast cancer recurrence, distant recurrence, death attributable to any cause, contralateral invasive breast cancer, or second non-breast invasive cancer. Note: In-situ events are not included.
I. Overall survival (OS). II. Recurrence-free survival (RFS). III. Adverse events. IV. Cardiac function/adverse events. V. Site of first recurrence.
I. The associations of adverse events and outcomes with each of the following will be examined: geriatric assessment (GA), patient reported outcomes (Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Event [PRO-CTCAE]), quality of life (QOL), and biomarkers of aging.
II. To determine whether clinician-reported CTCAEs are more accurate when PRO-CTCAE data are shared with the patient and clinician.
III. Utilize a high-throughput mutation profiling system (Oncomap) to query a large panel of cancer gene mutations in older patients with HER2-positive breast cancers.
Patients receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 6-12 months and then yearly for 4 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||ATOP Trial: Adjuvant Ado-Trastuzumab Emtansine (T-DM1) for Older Patients With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Breast Cancer|
|Actual Study Start Date :||April 10, 2015|
|Estimated Primary Completion Date :||January 31, 2022|
|Estimated Study Completion Date :||January 31, 2022|
Experimental: Treatment (trastuzumab emtansine)
Patients receive trastuzumab emtansine IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Biological: Trastuzumab Emtansine
- Invasive disease-free survival rate [ Time Frame: Up to 5 years post-treatment ]The entire invasive disease-free survival rate experience of evaluable patients will be summarized with a Kaplan-Meier curve. The 5-year invasive disease free survival landmark will be estimated from the Kaplan-Meier curve, and a 2-sided 90% confidence interval will be provided. A secondary efficacy analysis will use the log-rank test to compare the invasive disease free survival experience of this trial population with a similar population of older patients in a historical control cohort that received adjuvant chemotherapy + trastuzumab.
- Overall survival [ Time Frame: From study enrollment to death attributable to any cause (i.e. death from breast cancer, non-breast cancer cause, or from unknown cause), assessed up to 5 years ]A Kaplan-Meier curve will be used to summarize the overall survival experience of this patient cohort.
- Recurrence-free survival [ Time Frame: From study enrollment to disease recurrence and will not include death as an event, assessed up to 5 years ]Recurrence-free survival will be summarized with a Kaplan-Meier curve.
- Incidence of adverse events graded according to Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 12 months post-treatment ]Safety/adverse events data will be tabulated, including adverse events of all grades, in addition to cardiac dysfunction.
- Cardiac dysfunction defined as incidence of symptomatic left ventricular systolic dysfunction, cardiac death, and incidence of decrease in ejection fraction by at least 10 percentage points below baseline or to below 50% [ Time Frame: Up to 12 months post-treatment ]Safety/adverse events data will be tabulated, including adverse events of all grades, in addition to cardiac dysfunction.
- Site of first recurrence [ Time Frame: Up to 5 years ]The site of first recurrences will be tabulated as frequencies and relative frequencies.
- Overall rate of grade 3+ adverse events [ Time Frame: Up to 12 months ]Calculated using the baseline geriatric assessment measures. A score of 0 to 5 will be considered low risk, a score of 6 to 9 will be considered intermediate risk and a score of 10 to 19 will be considered high risk. A chi-square test will be done to determine if the rates of grade 3+ adverse events differ for these categories. In addition, the grade 3+ adverse event rates will be estimated for each category with a binomial estimator and corresponding 95% confidence interval and compared to the values obtained by Dr. Hurria. Occurrences of grade 3+ adverse events will be associated with geriatric assessment measurements.
- Change in geriatric assessment score [ Time Frame: Baseline to up to 12 months ]The average geriatric assessment score will be compared across the patient reported outcomes-Common Terminology Criteria for Adverse Events item scores using a repeated measure analysis of variance. Boxplots will be generated for each score for a particular patient reported outcomes-Common Terminology Criteria for Adverse Events item for the geriatric assessment score.
- Change in quality of life [ Time Frame: Baseline to up to 12 months ]The average quality of life score will be compared across the patient reported outcomes-Common Terminology Criteria for Adverse Events item scores using a repeated measure analysis of variance.
- Levels of inflammatory markers, coagulation, and senescence biomarkers [ Time Frame: Up to 12 months ]Boxplots will be used to summarize the biomarker values at each time point and spaghetti plots will be used to display changes in biomarker values over time for each patient. Whether each marker will be associated with grade 3+, adverse events, and disease-free survival will be determined using the appropriate model: a logistic regression model will be used for binary outcomes and cox proportional hazards model will be used for time-to-event outcomes. Changes in marker values over time will be analyzed to determine if they are associated with outcome using an appropriate linear mixed model.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02414646
|United States, California|
|City of Hope Comprehensive Cancer Center|
|Duarte, California, United States, 91010|
|United States, Illinois|
|Peoria, Illinois, United States, 61615|
|United States, Kansas|
|Cancer Center of Kansas - Wichita|
|Wichita, Kansas, United States, 67214|
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|United States, Michigan|
|Michigan Cancer Research Consortium NCORP|
|Ann Arbor, Michigan, United States, 48106|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|State University of New York Upstate Medical University|
|Syracuse, New York, United States, 13210|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|High Point Regional Hospital|
|High Point, North Carolina, United States, 27262|
|FirstHealth of the Carolinas-Moore Regional Hospital|
|Pinehurst, North Carolina, United States, 28374|
|United States, Ohio|
|Columbus NCI Community Oncology Research Program|
|Columbus, Ohio, United States, 43215|
|Toledo Clinic Cancer Centers-Toledo|
|Toledo, Ohio, United States, 43623|
|United States, Virginia|
|Inova Fairfax Hospital|
|Falls Church, Virginia, United States, 22042|
|Principal Investigator:||Rachel Freedman||Academic and Community Cancer Research United|