Cardiovascular Effects of Sunitinib Therapy (CREST)

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2013 by Abramson Cancer Center of the University of Pennsylvania
Sponsor:
Information provided by (Responsible Party):
Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT01370109
First received: May 26, 2011
Last updated: February 26, 2013
Last verified: February 2013
  Purpose

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.


Condition
Patients With Renal Cell Carcinoma Who Are Newly Initiating Therapy
With the Oral Tyrosine-kinase Inhibitor Sunitinib.

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Cardiovascular Effects of Sunitinib Therapy: Off Target Changes in Cardiac Metabolism and Ventricular Vascular Mechanics (CREST)

Resource links provided by NLM:


Further study details as provided by Abramson Cancer Center of the University of Pennsylvania:

Primary Outcome Measures:
  • Change from Baseline in Systolic Blood Pressure at 6 months. [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of Participants with adverse events [ Designated as safety issue: Yes ]
    Number of subjects with adverse events specifically, incident of hypertension and Cardiac dysfunction


Estimated Enrollment: 20
Study Start Date: April 2011
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

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.
  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: NCT01370109

Contacts
Contact: Bonnie Ky, MD 855-216-0098 PennCancerTrials@emergingmed.com

Locations
United States, Pennsylvania
Abramson Cancer Center, University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Bonnie Ky, MD    855-216-0098    PennCancerTrials@emergingmed.com   
Principal Investigator: Bonnie Ky, MD         
Sponsors and Collaborators
Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT01370109     History of Changes
Other Study ID Numbers: UPCC 34810
Study First Received: May 26, 2011
Last Updated: February 26, 2013
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on September 18, 2014