Kinetics of Troponin and BNP in Breast Cancer Chemotherapy With Adriamycin and Trastuzumab
This pilot study involves very frequent monitoring of breast cancer patient blood levels of hs-cTnT Troponin and n-t-BNP (Brain Natriuretic Peptide) before and after initiation of chemotherapy with either adriamycin or trastuzumab in order to define the kinetics of both biomarkers during the first two cycles of chemotherapy. Cardiac troponins and BNP are frequently elevated after experimental chemotherapy in animal models. Their behavior in humans has been inconsistent, with occasional elevations seen, usually within 30 days of therapy. Assays for troponin with sensitivity into the pg/ml range have now been introduced. A majority of patients greater than age 50 have elevations above the detection limit, compared to only 1-3% with conventional troponin assays, and over 90% of diabetics have elevations above the detection limit. Moreover, augmented release of high sensitivity troponin is detected after exercise or rapid atrial pacing of durations of 10-15 minutes in patients with and without coronary artery disease. This improved sensitivity suggests the potential for detection and monitoring of cardiac damage after cancer chemotherapy. We hypothesized that this new generation of troponin assay would be associated with kinetic behavior suggesting ongoing cardiac damage with anthracycline therapy, and possibly also with trastuzumab.
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||Pilot Study of the Kinetics of High Sensitivity Troponin and Brain Natriuretic Peptide in Breast Cancer Chemotherapy With Adriamycin and Trastuzumab|
- Area under the curve [ Time Frame: one year ] [ Designated as safety issue: Yes ]Concentration-time plots from pre-treatment through days 1,2,3,7,and pre-cycle two
- Baseline to peak [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]The difference between the pretreatment value and the highest level on days 1,2,3 or 7
- Descriptive statistics [ Time Frame: 1 year ] [ Designated as safety issue: No ]Descriptive statistics will be used to describe the quantitative values, and frequencies above and below the detection limit, time to peak, and amplitude of peak versus baseline values for both n-t-BNP and hs-cTnT.
Biospecimen Retention: Samples Without DNA
Whole blood 10 ml per draw, yielding 5 ml of serum. After testing, the remaining serum will be stored.
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||September 2015|
|Estimated Primary Completion Date:||September 2015 (Final data collection date for primary outcome measure)|
Patients with breast cancer beginning chemotherapy with a dose-dense regimen including adriamycin without concurrent trastuzumab.
Patients receiving trastuzumab in the adjuvant, neo-adjuvant, or metastatic setting in a regimen not containing simultaneous adriamycin therapy.
Collect blood samples in two groups of patients (n=10 per group) for amino-terminal brain natriuretic peptide (n-t-BNP) and high sensitivity cardiac troponin T (hs-cTnT):
- Group 1 (adriamycin) will consist of patients beginning clinically indicated chemotherapy for breast cancer with a dose-dense (every 2 week) regimen. including adriamycin (n=10).
- Group 2 will include patients who receive trastuzumab in the adjuvant or (neo) adjuvant setting, or in a metatstatic setting in a regimen that does not include simultaneous adriamycin.
Blood samples for hs-cTNT and n-t-BNP will be obtained on days pre-treatment, and post-treatment days 1, 2, 3, 7, pre-cycle 2, and post-cycle 2 days 1,2,3 and 7. The interval for treatment is usually two weeks for adriamycin and three weeks for trastuzumab. We will identify frequency of detectible levels above the detection limit and above the baseline, peak values and area under the curve. Enrollment of up to 15 per group will be allowed to guarantee acquisition of 10 full sets of samples. Lab draw from chemotherapy ports will be allowed. We plan to store specimens for future analyses with more sensitive assays in development.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01771549
|United States, Florida|
|Jacksonville, Florida, United States, 32224|
|Principal Investigator:||Joseph L Blackshear, M.D.||Mayo Clinic|