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

Completed

• Conditions: Unspecified Adult Solid Tumor, Protocol Specific

• Registration Number: NCT00691730
• Lead Sponsor: University Health Network, Toronto

Brief Summary

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.

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 Timeline

• Study Start: 2008-02
• Study First Submitted: 2008-06-04
• Study First Submitted QC: 2008-06-04
• Study First Posted: 2008-06-05
• Primary Completion: 2012-07
• Study Completion: 2019-04
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-25
• Last Update Posted: 2021-01-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Predictive value of soluble factors in the development of proteinuria or hypertension	Up to 8 weeks
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 steady state drug concentrations in the development of proteinuria or hypertension	Up to 8 weeks

Trial Locations

Locations (4)

London Regional Cancer Program; 🇨🇦 London, Ontario, Canada

Mount Sinai Hospital; 🇨🇦 Toronto, Ontario, Canada

University Health Network-Princess Margaret Hospital; 🇨🇦 Toronto, Ontario, Canada

Tom Baker Cancer Centre; 🇨🇦 Calgary, Alberta, Canada