Kinetics of Troponin and BNP in Breast Cancer Chemotherapy With Adriamycin and Trastuzumab

Breast Cancer Clinical Trial

Official title:

Pilot Study of the Kinetics of High Sensitivity Troponin and Brain Natriuretic Peptide in Breast Cancer Chemotherapy With Adriamycin and Trastuzumab

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01771549
• Other study ID #: 12-007541
• Status: Completed
• First received: January 14, 2013
• Last updated: March 21, 2018
• Start date: January 2013
• Est. completion date: June 26, 2017

Study information

• Verified date: March 2018
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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 metastatic 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: June 26, 2017
• Est. primary completion date: June 26, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Female adult patients aged 18+

• Group 1: beginning clinically- indicated chemotherapy for breast cancer with a dose-dense (every 2 weeks) regimen including adriamycin (n=10).

• Group 2: patients who receive trastuzumab in and adjuvant, (neo) adjuvant, or metastatic setting in a regimen that does not include simultaneous adriamycin.

Exclusion Criteria:

• Inability to return to the clinic for regular phlebotomy

• Baseline hemoglobin < 10 gm/dl

• Creatinine clearance < 60 ml/minute (this effects troponin clearance)

• Recent (< 3 months) cardiac surgery, myocardial infarction, unstable angina, or hospitalization for congestive heart failure

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Locations

Country	Name	City	State
United States	Mayo Clinic	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Mayo Clinic

Country where clinical trial is conducted

United States, 

References & Publications (1)

Advani P, Hoyne J, Moreno-Aspita A, Dubin M, Brock S, Harlow C, Chumsri S, Suter T, Blackshear JL. High-Sensitivity Troponin T and NT-proBNP Kinetics in Breast Cancer Chemotherapy. Chemotherapy. 2017;62(6):334-338. doi: 10.1159/000477797. Epub 2017 Jul 14 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Descriptive statistics	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.	1 year
Primary	Area under the curve	Concentration-time plots from pre-treatment through days 1,2,3,7,and pre-cycle two	one year
Secondary	Baseline to peak	The difference between the pretreatment value and the highest level on days 1,2,3 or 7	1 year