Clinical trial NCT01173341: Cardiotoxicity of Cancer Therapy (CCT)
Official title: Cardiotoxicity of Cancer Therapy: Mechanisms and Predictors
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Breast Cancer
Keywords: Chemotherapy-induced cardiotoxicity
Anthracycline
Trastuzumab
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2010-08-02
Enrollment: 700
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects with breast cancer will enter the cohort prior to chemotherapy initiation and be evaluated at baseline and at regular intervals during the first approximately 15 months after chemotherapy is initiated. Patients will have study visits at 2 years, 3 years, 5, years, 7 years, 9 years, 11 years, 13 years, and 15 years following initiation of cancer therapy.

Brief summary: The objective of this study is to define the clinical significance of mechanistic biomarkers (including Neuregulin-1Beta) and novel echocardiographic measures of cardiac function in predicting the incident risk of cancer therapy cardiotoxicity.

Detailed description: The overall study objectives are:

1. To determine the longitudinal relationships between circulating markers, such as Neuregulin (NRG)-1Beta levels and incident risk of adverse cardiovascular outcomes in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that a sustained increase in NRG-1Beta, indicative of enhanced cardiac stress with exposure to chemotherapeutic agents, is predictive of an increased risk of cardiac dysfunction and heart failure.
2. To study the single nucleotide polymorphism (SNP)/haplotype variation in pathways of interest, such as the Neuregulin/Epidermal Growth Factor (ErbB) signaling pathway, on incident risk of adverse cardiovascular outcomes. We hypothesize that there will be SNP/haplotypes variations that are associated with incident cardiovascular outcomes.
3. To determine the longitudinal relationships between novel echocardiographic measures, such as strain and strain rate and incident cardiac dysfunction in patients exposed to anthracycline, trastuzumab, or a combination of the two agents. We hypothesize that early declines in strain and strain rate are predictive of an increased risk of future cardiac dysfunction and heart failure.
4. To explore the changes in biomarkers such as NRG-1Beta levels and the relationships with novel echocardiographic measures of cardiac function.
5. To create a biobank as a future resource for additional questions in novel biomarkers and genetics.
6. To determine the long-term effects of cancer therapy cardiotoxicity by following patients yearly for 5 years after their exposure to cancer therapy, with the option to extend up to an additional 5 years.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older
* HER-2 positive breast cancer designated to receive trastuzumab chemotherapy with or without prior exposure to anthracycline-based chemotherapy
* Non-HER-2 positive breast cancer designated to receive treatment with an anthracycline-containing regimen

Exclusion Criteria:

* Other contraindications to trastuzumab or anthracycline chemotherapy.
* Vulnerable populations

Primary outcomes:
measure: Cardiac dysfunction or signs or symptoms of heart failure
timeFrame: 15 years
Secondary outcomes:
measure: Change in quantitated Left Ventricular Ejection Fraction (LVEF)
timeFrame: 15 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center
name: Bonnie Ky, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Demissei BG, Hubbard RA, Zhang L, Smith AM, Sheline K, McDonald C, Narayan V, Domchek SM, DeMichele A, Shah P, Clark AS, Fox K, Matro J, Bradbury AR, Knollman H, Getz KD, Armenian SH, Januzzi JL, Tang WHW, Liu P, Ky B. Changes in Cardiovascular Biomarkers With Breast Cancer Therapy and Associations With Cardiac Dysfunction. J Am Heart Assoc. 2020 Jan 21;9(2):e014708. doi: 10.1161/JAHA.119.014708. Epub 2020 Jan 21.
citation: Upshaw JN, Finkelman B, Hubbard RA, Smith AM, Narayan HK, Arndt L, Domchek S, DeMichele A, Fox K, Shah P, Clark A, Bradbury A, Matro J, Adusumalli S, Carver JR, Ky B. Comprehensive Assessment of Changes in Left Ventricular Diastolic Function With Contemporary Breast Cancer Therapy. JACC Cardiovasc Imaging. 2020 Jan;13(1 Pt 2):198-210. doi: 10.1016/j.jcmg.2019.07.018. Epub 2019 Sep 18.
citation: Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, Lunde IG, Wakimoto H, Smith AM, Toepfer CN, Getz K, Gorham J, Patel P, Ito K, Willcox JA, Arany Z, Li J, Owens AT, Govind R, Nunez B, Mazaika E, Bayes-Genis A, Walsh R, Finkelman B, Lupon J, Whiffin N, Serrano I, Midwinter W, Wilk A, Bardaji A, Ingold N, Buchan R, Tayal U, Pascual-Figal DA, de Marvao A, Ahmad M, Garcia-Pinilla JM, Pantazis A, Dominguez F, John Baksi A, O'Regan DP, Rosen SD, Prasad SK, Lara-Pezzi E, Provencio M, Lyon AR, Alonso-Pulpon L, Cook SA, DePalma SR, Barton PJR, Aplenc R, Seidman JG, Ky B, Ware JS, Seidman CE. Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy. Circulation. 2019 Jul 2;140(1):31-41. doi: 10.1161/CIRCULATIONAHA.118.037934. Epub 2019 Apr 16.