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

University Health Network, Toronto

Status: Completed

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Other: laboratory biomarker analysis

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT00691730

CDR0000588665 (Registry Identifier)

PHL-064

PMH-PHL-064

NCI-2009-00277 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 52 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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