Experimental Therapeutics Program at The Children’s Hospital

from Practice Update, Summer 2005

* Lead Institutions
• POETIC Institutions
ϑ States where patients, inquiries, consults are drawn from
One third of all pediatric cancer patients are treated at these institutions.

The goal of the Experimental Therapeutics Program (ETP) within the Center for Cancer and Blood Disorders is to promote the development, scientific support and clinical translation of promising therapies for the treatment of children, adolescents and young adults with cancer and related disorders. The ETP at Children’s is the only comprehensive basic and translational research-based program that can provide direct access to and application of these resources to the clinical care of pediatric, adolescent and young adult cancer patients in an eleven-state region. Because of strong academic affiliations locally and nationally, the ETP at Children’s can provide access to new treatments and treatment modalities only available at few highly select academic institutions across the country. Patients come for treatment through the ETP because they have cancer that has not responded to traditional, standard treatments. New therapies are promising, but they require a highly specialized system which ensures patient safety and the proper gathering of information in order to decide the usefulness of these treatments.

“Every drug we use today has been through a development process that can take many, many years,” said Lia Gore, Director of the ETP. “Kids with cancer sometimes cannot afford to wait for that long.” The goal of the ETP is to bring new and promising treatments to the forefront of cancer therapy. “Doing this is complicated—we need to make sure that we offer every child the best possible chance to benefit from participating in one of the trials we have, while continuing to look at the big picture,” said Gore.

Goals

The ETP at The Children’s Hospital is committed to:

• Incorporate basic science and biologic correlative studies that facilitate the translation between basic science and clinical research within The Children’s Hospital Center for Cancer and Blood Disorders, the University of Colorado Health Sciences Center, the University of Colorado Cancer Center, National Jewish Health, and other major academic pediatric medical centers around the country
• Design and conduct early phase clinical trials with a primary emphasis on rational, biologically-based drug development
• Increase patient access to early phase clinical trials
• Identify and develop new agents and novel therapeutic strategies that target specific disease mechanisms, thus promoting and improving quality of life
• Foster further development and evaluation of promising agents and of novel combinations of agents in subsequent larger scale Phase II and III clinical trials

Basic and Translational Science

A critical function of the ETP is to facilitate the translation of the basic science laboratory efforts within the division into effective clinical application to advancements in patient care. One of the unique aspects of the ETP is that new discoveries made by the laboratory-based faculty at the University of Colorado Health Sciences Center are discussed directly with the clinical researchers who can help develop and apply the findings to patient applications at an early stage. By making direct connections between the basic and translational science component, collaborating with other faculty within the University of Colorado system, both at the Health Sciences Center and the Boulder campuses, as well as the pharmaceutical industry, and generating comprehensive concept development plans for areas of special interest with the clinical researchers, the ETP is uniquely positioned to generate rationally-designed, biologically-targeted treatment strategies and compounds.

Clinical trials

The ETP staff and their colleagues within the University of Colorado Health Sciences Center and the Center for Cancer and Blood Disorders at The Children’s Hospital have expertise in all aspects of clinical trial development and conduct the necessary biologic correlative studies including pharmacokinetics, pharmacodynamics, pharmacogenetics, biostatistical design and analysis, functional imaging capabilities, and correlative molecular studies. Membership in the University of Colorado ’s NCI-designated Comprehensive Cancer Center provides The Children’s Hospital ETP physicians:

• On-site NIH-funded pediatric and general Clinical Research Centers (CRC)
• Active collaborations with the NCI-funded Developmental Therapeutics programs for adults
• Access to the Translational Research Laboratory
• Access to the Cancer Pharmacology Core Research Laboratory

Dr. Lia Gore is responsible for the clinical development of translational studies conducted with Doctors Timothy Garrington, Doug Graham and Deborah DeRyckere; the collaborations of the faculty fuel the success of the studies. The multidisciplinary faculty’s memberships include the Children’s Oncology Group (COG), the Southwest Oncology Group (SWOG), the Radiation Therapy Oncology Group (RTOG) and the Gynecologic Oncology Group (GOG). Only by a concerted multidisciplinary approach such as this, can the translation of basic science discovery be rapidly translated to the clinical care of children with cancer. A cooperative approach among all these persons and elements are critical to accomplish these goals.

In order to help accomplish the goals of the ETP at The Children’s Hospital, in 2002, Dr. Gore co-founded the Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC) with Tanya Trippet, MD, at Memorial Sloan-Kettering Cancer Center in New York City . POETIC is composed of ten large academic medical centers in the U.S. and Canada , with a major emphasis on comprehensive cancer care and research. Member institutions serve a geographically and ethnically diverse patient population, and treat one-third of all relapsed pediatric oncology patients in the country. Relapsed pediatric patients are the target population for entry into Phase I and II clinical trials. Each member institution is a well-recognized leader in cancer research, and together, POETIC represents an outstanding group of institutions known for their cutting edge work in the fight against cancer.

Dedicated staff to the ETP include Debra Schissel, RN, Molly Hemenway, PNP, and Pamela Bowry, Program Coordinator. Resources within the Center for Cancer and Blood Disorders at Children’s are vital to the success of the ETP. “None of this could happen without the support and on-going activity in hematology/oncology. I am indebted to my colleagues, who provide the kind of environment that allows a new program to grow,” said Gore. In addition, the ETP at Children’s is making a name for itself among research institutions all over the country. They have been asked to train research nurses from three other pediatric hospitals in the proper way to set up and administer a clinical trials program. “That feels pretty good—to be recognized that we do good work by our peers,” said Gore.

In addition, the multi-specialty services available at Children’s, including Pediatric Surgery, orthopedics, Neurosurgery, Radiology, Laboratory, Blood Bank, and Pharmacy services are critical to the success of the ETP. “None of this happens in a vacuum,” says Gore. “Only at a place like Children’s, with commitment to the kids at every step, can something like this work. These kids are too sick and their diseases are too complicated to ask for anything less than the best. Fortunately, we have that here.”