Kidney and Blood Pressure Changes in Patients Receiving Bevacizumab, Aflibercept, Sunitinib, or Cediranib for Cancer (NCI 8076)

The Role of VEGF-A Signaling in Maintenance of the Glomerular Filtration Barrier and Blood Pressure

This research study is looking at kidney and blood pressure changes in patients receiving bevacizumab, aflibercept, sunitinib, or cediranib for cancer. Studying samples of blood and urine from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment with an antiangiogenic drug.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: laboratory biomarker analysis

Detailed Description

OBJECTIVES:

I. To study the renal and blood pressure changes in patients treated with bevacizumab, aflibercept, sunitinib malate, or cediranib for their cancer.

II. To determine the physiological mechanisms behind proteinuria and hypertension induced by antiangiogenic therapies (i.e., rarefaction; imbalance in eNOS, prostacyclin [PGI_2], prostaglandin E2 [PGE_2], and thromboxane A2 [TXA2]; renin/aldosterone; or renovascular hypertension).

III. To determine whether soluble factors (like tyrosine kinase 1 [sFlt1], bFGF, and VEGF) and steady state drug concentration are predictive of the development of proteinuria/hypertension.

OUTLINE: This is a multicenter study.

Patients undergo blood and urine sample collection periodically. Urine samples are assessed for PGI2 and TXA2 levels using validated ELISA methods. Urine is also assessed for protein and creatinine levels, microalbumin, osmolality, and electrolytes. Blood samples are assessed for pharmacokinetics and sFlt1, VEGF, and bFGF levels by validated ELISA methods. Blood samples are also assessed for steady state drug concentration, renin, and aldosterone levels.

• Study Type: Observational
• Enrollment (Actual): 52

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital

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: Non-Probability Sample

Study Population

Patients who are going to start treatment with bevacizumab, VEGF Trap, sunitinib or AZD2171.

Description

Inclusion Criteria:

• Planning to start treatment with one of the following antiangiogenic drugs as single agents or in combination with chemotherapy for their cancer:

  • Cediranib (AZD2171 )
  • Bevacizumab (Avastin)
  • Sunitinib (Sutent)
  • Aflibercept (VEGF Trap)
• Urinalysis negative for protein OR 24-hour urine for protein < 500 mg
• Prior chemotherapy within the past 12 months allowed
• More than 12 months since prior antiangiogenic drugs, including monoclonal antibodies that bind to VEGF or tyrosine kinase inhibitors that block VEGFR2
• At least 6 weeks since prior and no concurrent aldosterone receptor antagonists (e.g., spironolactone [aldactone] or eplerenone)
• No other concurrent investigational agents

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Renal and blood pressure changes	Up to 8 weeks
Physiological mechanism behind proteinuria and hypertension induced by antiangiogenic therapies	Up to 8 weeks
Predictive value of soluble factors in the development of proteinuria or hypertension	Up to 8 weeks
Predictive value of steady state drug concentrations in the development of proteinuria or hypertension	Up to 8 weeks

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Malcolm Moore, University Health Network-Princess Margaret Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2008
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): April 1, 2019

Study Registration Dates

• First Submitted: June 4, 2008
• First Submitted That Met QC Criteria: June 4, 2008
• First Posted (Estimate): June 5, 2008

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: PHL-064; NCI-2009-00277 (Other Identifier: CTRP (Clinical Trials Reporting System)); PMH-PHL-064; CDR0000588665 (Registry Identifier: PDQ (Physician Data Query))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No