With an $8.9 million grant from the National Cancer Institute, nine
institutions have joined forces to develop and test new treatments for
neuroblastoma, an aggressive cancer that only strikes children. The principal
investigator of the NCI project program grant to develop those new therapies is
Robert C. Seeger, MD, of Childrens Hospital Los Angeles and the University of
Southern California. UCSF pediatric oncologist Katherine K. Matthay, MD, is
principal investigator of the clinical consortium, New Approaches to
Neuroblastoma Therapy (NANT), which aims to bring to the bedside the most
promising strategies to improve the outcome of children with this disease.
Neuroblastoma is the most common cancer among infants and the second most
common solid tumor malignancy in children under five. At the time they are
diagnosed, 45 percent of affected children have high-risk disease, with the
cancer often spreading throughout the body. A nationwide Phase III clinical
trial led by Matthay, who is director of pediatric clinical oncology at the
Children’s Medical Center at UCSF, last year showed a three-fold improvement in
disease-free survival from high-risk neuroblastoma due to a new combination of
therapies. But even with this improvement, only 40 percent of children with the
most dangerous form of neuroblastoma survive for five years without a
“In spite of the best therapies we have available, neuroblastoma recurs in many
children affected by it, and those children have a poor prognosis,” said
Matthay. “That is why we formed this new consortium.”
Seeger, who is professor of hematology/oncology and deputy director of research
at Childrens Hospital Los Angeles and the Department of Pediatrics at the Keck
School of Medicine at the University of Southern California, said that the NCI
project program grant will allow investigators at the nine institutions to
share research information and potentially speed the development of strategies
that will enhance the effectiveness of current therapies.
“Our goal is to improve disease-free survival for 90 percent or more of
children with neuroblastoma,” Seeger said.
Four different laboratory-based projects will investigate the promise of
different strategies to stop tumors and their metastases, by targeting drugs to
neuroblastoma tumors and by enhancing the drugs’ effectiveness at killing even
those cancer cells that are resistant to other drugs. Those projects will be
led by investigators at Childrens Hospital Los Angeles (CHLA), the University
of Indiana and the University of Southern California.
The fifth major project of the study, led by Matthay, will translate the most
promising of these strategies into small-scale Phase I - II clinical trials,
offered to children in the context of the best current treatment for their
stage of neuroblastoma. If these steps show that a strategy can be delivered
safely, and show evidence that it will be effective, the method will be offered
to the nationwide NCI-sponsored children’s cancer research networks for
large-scale Phase III clinical trials.
Such large-scale nationwide trials, with many institutions working together,
are credited with major advances against childhood cancer in the past 25 years.
Some children’s cancers have high cure rates, and treatments for others have
improved. Seeger, Matthay and their colleagues expect that the NANT project
will speed the process of offering treatments for this particularly
recalcitrant form of cancer—and may be applicable to other childhood and
adult malignancies as well.
The nine NANT institutions are: Childrens Hospital Los Angeles/USC; the
Children’s Medical Center/UCSF; Lucile Packard Children’s Hospital/Stanford
University; the University of Wisconsin; the University of Michigan; Cincinnati
Children’s Hospital; the University of Minnesota; the University of Indiana,
and Children’s Hospital of Philadelphia/University of Pennsylvania.
The Children’s Medical Center at UCSF has been providing specialized care to
children since 1913. Children come to UCSF from throughout the western United
States and around the world for expert treatment of cancer; heart defects,
other congenital anomalies and other major diseases.