Clinical trial NCT00691730: Kidney and Blood Pressure Changes in Patients Receiving Bevacizumab, Aflibercept, Sunitinib, or Cediranib for Cancer
Official title: The Role of VEGF-A Signaling in Maintenance of the Glomerular Filtration Barrier and Blood Pressure
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-06-05
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients who are going to start treatment with bevacizumab, VEGF Trap, sunitinib or AZD2171.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Renal and blood pressure changes
timeFrame: Up to 8 weeks
measure: Physiological mechanism behind proteinuria and hypertension induced by antiangiogenic therapies
timeFrame: Up to 8 weeks
measure: Predictive value of soluble factors in the development of proteinuria or hypertension
timeFrame: Up to 8 weeks
measure: Predictive value of steady state drug concentrations in the development of proteinuria or hypertension
timeFrame: Up to 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network-Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: University Health Network-Princess Margaret Hospital
name: Malcolm Moore
role: PRINCIPAL_INVESTIGATOR
References: