First Multiple Drug Trial to Attack Blood Vessel Formation in Kidney Cancer
PHILADELPHIA â€“ In the first clinical trial of its kind, researchers at the University of Pennsylvania School of Medicine and the Abramson Cancer Center will lead a nationwide test of anti-cancer drug combinations that target blood vessel growth in patients with advanced kidney cancer. The trial is being conducted with colleagues in the Eastern Cooperative Oncology Group, a network of researchers, physicians, and health care professionals at public and private institutions.
In addition to these patients, the results from the trial will inform care in many other types of cancer, including breast, lung, and colon cancer. Penn scientists will also use an experimental imaging technique to measure the effectiveness of the treatments.
The BeST trial stands for bevacizumab(Avastinterm), sorafenib(Nexavartermterm), and temsirolimus(Torisel), Researchers have previously shown these drugs to slow the progression of metastaticterm cancer when used alone by starving the cells of the oxygenated blood required for growth.Â
â€œThis trial takes these three proven drugs, and combines them into two drug combinations,â€ said Keith Flaherty, MD, Assistant Professor of Medicine, who is the primary investigator for the trial. â€œThey all seem to attack blood vessel formation in somewhat unique ways, so we think we could get a more profound effect by combining them.
â€œIn my mind, kidney cancer is truly the anvil on which we will hammer out the issues of anti-angiogenic therapy because it is the disease where we donâ€™t give chemotherapyterm or any other type of drug at the same time and we can still see benefit. It is in this setting that we are going to work out which combinations make sense, are safe, and efficacious. And then move those into other cancers,â€ Flaherty said.
Flaherty and colleagues will determine which of the drug treatments â€“ sorafenibterm plus bevacizumabtermterm, sorafenib plus temsirolimusterm, temsirolimus plus bevacizumab, or bevacizumab alone â€“ is most effective by looking at how long it takes patientsâ€™ tumors to start growing again on treatment. The longer the progression-free survival is, the better the combination.
In addition to this standard measure of effectiveness, Mark Rosen, MD, PhD, Assistant Professor of Radiology, will lead the imaging portion of the trial to test the value of a relatively new imaging technique in evaluating anti-angiogenic therapy. The technique, called dynamic contrast-enhanced-magnetic resonance imaging, or DCE-MRI, relies on a series of rapidly collected images that allow the investigators to calculate the rate of movement of a contrast agent through the blood vessels and into the tumor. Using this information they can estimate the amount and rate of blood flow. Researchers may be able to use that information to learn within a few days or weeks whether a patient is responding to anti-angiogenic therapy, rather than having to wait months to see if a patientâ€™s disease worsens or gets better.
When Rosen tested DCE-MRI in a small group of patients that Flaherty treated in a pilot study with sorafenib, he identified tumor characteristics that predict response to therapy. â€œWe want to know if these characteristics remain predictive in a larger patient population,â€ Rosen said. â€œAlso, we want to see if we can get high quality DCE-MRI data from multiple institutions. It is one thing to succeed in a small group of patients here, but DCE-MRI is not something that one can get by pushing a button on a machine. Obtaining high quality DCE-MRI results when the imaging is performed across multiple institutions may be more difficult, but is a crucial step in defining the applicability of the DCE-MRI technique in the routine clinical setting.â€
The BeST trial is sponsored by the Eastern Cooperative Oncology Group and supported by grants from the National Cancer Institute. The imaging portion of the trial is supported by the National Cancer Institute as part of the I-2 initiative to improve imaging techniques in cancer care.
For more information on the study and how to enroll, please visit the study website at the National Institutes of Health: http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=499788&version=patient&protocolsearchid=3677344