A clinical trial testing a genetically
reprogrammed herpes simplex virus as treatment for deadly forms of
childhood cancer has received a U.S. Food and Drug Administration grant
to support the research.
Phase I trial at Cincinnati Children’s Hospital Medical Center currently
focuses on testing the safety of the agent HSV1716 in patients. The
study includes young patients with solid tumors such as rhabdomyosarcoma
or Ewing’s sarcoma. These cancers have limited treatment options and
survival rates under 30 percent when the cancers recur and spread to
other parts of the body.
curves for stubborn, metastatic childhood cancers have leveled off in
the last decade, underscoring the need for new therapeutic approaches,
says Timothy Cripe, M.D., Ph.D.,
principal investigator on the trial and a physician/researcher in
division of Hematology/Oncology at Cincinnati Children’s.
exhausted our ability to improve cure rates with existing conventional
therapies, and we need new solutions,” he said. “This is why we are
testing HSV. It’s a potent virus that has been manipulated genetically
with the intent of making it safe for the patient. When you’re trying to
fight fire with fire you need something that is strong.”
grant from FDA is part of a program encouraging clinical development of
“orphan drugs” as new treatments for rare diseases or conditions. The
HSV1716 virus being tested in this trial was developed by Crusade
Laboratories of Glasgow, Scotland.
is similar to other viruses now under development by Dr. Cripe and
colleagues at Cincinnati Children’s in that certain genes are removed so
the virus does not infect healthy dormant cells or cause the disease in
the recipient. Instead, the genetic manipulation is designed to prompt
the virus to target, infect and degrade only rapidly dividing cancer
information also can be added to HSV that programs the virus to attack
cancer cells in other ways – such as activating certain types of
chemotherapies in a one-two punch or destroying blood vessels that feed
tumors. Research in mouse models of human cancer by Cripe’s laboratory
has shown oncolytic HSV agents to be effective at shrinking a variety of
modeled tumor types, suggesting a possible approach for treating human
goal in the current HSV1716 trial is to light a fire to the cancer so
that the virus replicates and spreads to the cancer cells,” Dr. Cripe
explained. “We have to take this one step at a time, and the initial
phase of the trial focuses on making sure the virus doesn’t cause
adverse side effects. It has been tested in Europe in adults with brain cancer, squamous cell carcinoma and melanoma and shown in those trials to be safe.”
HSV1716 has also been tested extensively for safety in animal models at Cincinnati Children’s Hospital by Dr. Cripe and in Europe prior to it being tested in people.
Phase I trial will include up to 18 patients and is expected to last
three years. The optimum safe dosing for this virus is unknown, so the
study will sequentially increase dosing levels in small groups of
patients and observe for side effects as the trial proceeds. This
earliest phase tests the lowest dose on older children and young adults
with solid tumor cancers who have limited or no standard therapy options
researchers plan to add younger patients with earlier stages of cancer
as the trial proceeds. They will not be able to determine if the safety
trial is successful until all patients have received treatment and the
results analyzed. As with all clinical trials of new anticancer
therapies in patients, many factors can influence the risk for severe
side effects and anticancer activity. Even though HSV1716 may cause
tumor shrinkage in mouse models of pediatric cancer, it may not have
antitumor effect in patients.
Initial funding for the trial came from a private foundation, Solving Kids Cancer, of New York.
Preclinical research that helped lead to the trial was supported by the
American Cancer Society, the National Cancer Institute, the Cincinnati
Children’s Hospital Medical Center Translational Research Initiative and
local foundations, including CancerFree Kids, teeoffagainstcancer.org,
the Katie Linz Foundation, The Sarah Zepernick Foundation, the
TeamConnor Cancer Foundation and money donated in memory of Katie McKenna Cappel and Zachary Heringer.
For more information about the HSV1716 pediatric trial, please visit:
To view a video slideshow about the trial, visit: http://www.youtube.com/watch?v=XLPzrRLuZoY