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

NCT ID: NCT01771549

Last Updated: 2018-03-23

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 26 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2017-06-26

Brief 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.

Detailed 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.

Conditions

Breast Cancer

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

Group 1

Patients with breast cancer beginning chemotherapy with a dose-dense regimen including adriamycin without concurrent trastuzumab.

No interventions assigned to this group

Group 2

Patients receiving trastuzumab in the adjuvant, neo-adjuvant, or metastatic setting in a regimen not containing simultaneous adriamycin therapy.

No interventions assigned to this group

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Joseph L. Blackshear

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph L Blackshear, M.D.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Mayo Clinic

Jacksonville, Florida, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 28704807 (View on PubMed)

Other Identifiers

12-007541

Identifier Type: -

Identifier Source: org_study_id