Cardiovascular Effects of Sunitinib Therapy (CREST)

The Cardiovascular Effects of Sunitinib Therapy: Off Target Changes in Cardiac Metabolism and Ventricular Vascular Mechanics (CREST)

Tyrosine kinase inhibitors such as sunitinib are used in the treatment of renal cell carcinoma and have significant off-target effects with cardiac toxicity and resultant ventricular cardiac dysfunction being a major concern. However, the mechanisms of these effects in humans remains poorly defined, as are the clinical methods to risk stratify and identify patients who will ultimately suffer from cardiac dysfunction. The goal of this multi-center study is to characterize the cardiovascular measures of cardiac function; 2) comprehensive measures of arterial function and left ventricular afterload; 3) biomarkers reflective of the pathophysiologic alterations. Through this work, the investigators will translate our basic understanding of sunitinib cardiotoxicity to humans and identify early predictors of sunitinib cardiotoxicity.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma 4

Detailed Description

Tyrosine kinase inhibitors such as sunitinib have dramatically improved the overall management of certaincancers including renal cell carcinoma. However, recent data suggest that these therapieshave significant off-target effects with cardiac toxicity, including significant hypertension and ventricular cardiac dysfunction being a major concern. However, the biologic mechanisms underlying cardiotoxicty in humans remain poorly defined. Moreover, there is a critical need to develop methods to improve the risk stratification and early identification of patients who will suffer from hypertension and cardiac dysfunction with exposure to therapy. The over all objectives ofthis study are to further characterize the cardiovascular changes that occur with sunitinib exposure in order to improve our understanding of sunitib toxicity and determine early, mechanistically and clinically relevant predictors to identify patients at increased risk of hyptertension and cardiac dysfunction. The specific aims of this study are: 1) To define the changes in arterial hemodynamics that may occur with exposure to sunitinib, 2) To define the changes in sensitive echocardiographic measures of cardiac function that may occur with exposure to sunitinib, 3) To determine blood markers that are associated with changes in vasculature or cardiac function with exposure to sunitinib. and 4) To determine if there are early imaging or biomarker predictors of subitinib cardiotoxicity.

• Study Type: Observational
• Enrollment (Actual): 98

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center, University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Our target population is patients with renal cell carcinoma who are newly initiating therapy with the oral tyrosine-kinase inhibitor sunitinib.

Description

Inclusion Criteria:

• Patients with renal cell carcinoma newly undergoing therapy with sunitinib.
• Age greater than or equal to 18 years
• ECOG performance status 0,1,2

Exclusion Criteria:

• Any contraindication to sunitinib therapy of note, patients with prior cardiovascular history are not excluded from this study, as long as there are no contraindications to sunitinib therapy.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Penn Site; Patients with renal cell cancer newly undergoing therapy with the oral tyrosine kinase inhibitor sunitinib will be recrutied and observed over a period of approximately 33 weeks, with additional follow-up at 1 and 2 years.
Vanderbilt University Medical Center; Patients with renal cell cancer newly undergoing therapy with the oral tyrosine kinase inhibitor sunitinib will be recrutied and observed over a period of approximately 33 weeks.
Case Medical Center; Patients with renal cell cancer newly undergoing therapy with the oral tyrosine kinase inhibitor sunitinib will be recrutied and observed over a period of approximately 33 weeks.
University of Wisconsin at Madison; Patients with renal cell cancer newly undergoing therapy with the oral tyrosine kinase inhibitor sunitinib will be recrutied and observed over a period of approximately 33 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline in Systolic Blood Pressure	6 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with adverse events	Number of subjects with adverse events specifically, incident of hypertension and Cardiac dysfunction	2 years

Collaborators and Investigators

• Sponsor: Abramson Cancer Center of the University of Pennsylvania
• Investigators: Principal Investigator: Bonnie Ky, MD, Abramson Cancer Center at the University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2011
• Primary Completion (Actual): December 31, 2017
• Study Completion (Actual): December 31, 2017

Study Registration Dates

• First Submitted: May 26, 2011
• First Submitted That Met QC Criteria: June 8, 2011
• First Posted (Estimate): June 9, 2011

Study Record Updates

• Last Update Posted (Actual): October 2, 2018
• Last Update Submitted That Met QC Criteria: October 1, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell
• Other Study ID Numbers: UPCC 34810