Clinical trial NCT01370109: Cardiovascular Effects of Sunitinib Therapy (CREST)
Official title: The Cardiovascular Effects of Sunitinib Therapy: Off Target Changes in Cardiac Metabolism and Ventricular Vascular Mechanics (CREST)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Renal Cell Carcinoma 4
Lead sponsor: Abramson Cancer Center at Penn Medicine
Sponsor class: OTHER
First posted: 2011-06-09
Enrollment: 98
Sex: ALL
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: Our target population is patients with renal cell carcinoma who are newly initiating therapy with the oral tyrosine-kinase inhibitor sunitinib.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change from Baseline in Systolic Blood Pressure
timeFrame: 6 Months
Secondary outcomes:
measure: Number of Participants with adverse events
timeFrame: 2 years
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Abramson Cancer Center, University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Abramson Cancer Center at the University of Pennsylvania
name: Bonnie Ky, MD
role: PRINCIPAL_INVESTIGATOR
References: