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

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Joseph L. Blackshear, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT01771549
First received: January 14, 2013
Last updated: January 20, 2014
Last verified: January 2014
  Purpose

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.


Condition
Breast Cancer

Study Type: Observational
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

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • 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.


Estimated Enrollment: 20
Study Start Date: January 2013
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
Group 1
Patients with breast cancer beginning chemotherapy with a dose-dense regimen including adriamycin without concurrent trastuzumab.
Group 2
Patients receiving trastuzumab in the adjuvant, neo-adjuvant, or metastatic setting in a regimen not containing simultaneous adriamycin therapy.

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Mayo Clinic Florida female, adult patients from Hematology/Oncology Department undergoing clinically-indicated treatment for breast cancer which includes either, but not both, adriamycin or trastuzamab will be eligible to participate

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01771549

Locations
United States, Florida
Mayo Clinic
Jacksonville, Florida, United States, 32224
Sponsors and Collaborators
Mayo Clinic
Investigators
Principal Investigator: Joseph L Blackshear, M.D. Mayo Clinic
  More Information

No publications provided

Responsible Party: Joseph L. Blackshear, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01771549     History of Changes
Other Study ID Numbers: 12-007541
Study First Received: January 14, 2013
Last Updated: January 20, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mayo Clinic:
Adriamycin
Trastuzumab
Brain Natriuretic Peptide (BNP)
Troponin

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Doxorubicin
Trastuzumab
Natriuretic Peptide, Brain
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Natriuretic Agents
Physiological Effects of Drugs
Cardiovascular Agents

ClinicalTrials.gov processed this record on July 23, 2014