Clinical Trials Continue the Advancement of Pediatric Oncology Treatment

Children, adolescents and young adults with cancers that do not respond to traditional treatments continue to find new treatment options because of CHOC’s extensive efforts and active engagement in clinical trial research.

The Hyundai Cancer Institute at CHOC Children’s is a member of the Children’s Oncology Group (COG) and one of only 21 elite facilities in North America and three in California that has received a prestigious Phase 1 clinical trial designation to offer COG’s investigational, potentially promising and innovative clinical trials. COG is the most experienced organization in the world when it comes to the research and development of new therapeutics for children and adolescents with cancer.

“I’ve witnessed the dramatic progress made in the survival of our pediatric patients because of clinical trials,” says Dr. Ivan Kirov, medical director of oncology and the Hyundai Cancer Institute at CHOC Children’s. “Clinical trials are the mortar behind our successes here at CHOC.”

Dr. Ivan Kirov, medical director of oncology and the Hyundai Cancer Institute at CHOC Children’s
Dr. Ivan Kirov, medical director of oncology and the Hyundai Cancer Institute at CHOC Children’s

CHOC currently offers more than 140 clinical trials in varying phases, including multiple pharmaceutical industry-sponsored clinical trials. Besides membership in COG, CHOC is also a member of the Therapeutic Advances in Childhood Leukemia & Lymphoma consortium (TACL), which offers novel treatments in Phase 1 studies for childhood leukemia and lymphoma; the Lymphoma consortium; and the UC Children, Adolescent and Young Adults Cancer Consortium, which includes all of the University of California pediatric oncology programs.

Among the research at CHOC is an upcoming clinical trial for the treatment of diffuse intrinsic pontine glioma (DIPG), a highly aggressive and one of the most difficult-to-treat childhood tumors.

“We are in the process of opening and initiating this clinical trial which, in my opinion, will be extremely important for patients in the future,” Dr. Kirov says. “DIPG is a brainstem tumor which is universally deadly, and very few patients survive more than a year, or even six months. CHOC, the Dana-Farber Cancer Institute in Boston and Lurie Children’s Hospital in Chicago are the only three sites where this new study will be offered. This study will explore a new vaccine for the treatment of DIPG in combination with checkpoint inhibitors. We’re hoping this study will be open in the next several months to offer hope to patients with this disease.”

While clinical research is fundamental to advancing pediatric oncology treatments, Dr. Kirov said the trials themselves are only part of CHOC’s comprehensive approach to helping children and young adults survive cancer.

“These cutting-edge medications and products we are testing, including new targeting agents, monoclonal antibodies and various types of small molecules and vaccines, for example, require an extremely strong supportive and clinical research infrastructure, which CHOC can offer,” says Dr. Kirov. “Our highly educated clinical research coordinators, physicians-scientists, nurses, educators, pharmacists, and other professionals, along with our unparalleled supportive services for both patients and their families, such as social workers, psychologists, child life specialists, palliative care experts and spiritual services, make our patients’ experiences at CHOC unique, and I think this is why CHOC truly stands out. In fact, many patients who come to CHOC for Phase 1 studies express their desire to stay here even after the study is completed, which really speaks very highly of CHOC and the continuum of care and support we provide to young patients and their families.”

Our Care and Commitment to Children Has Been Recognized

CHOC Children’s Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the cancer specialty.

Learn how CHOC’s pediatric oncology treatments, expertise and support programs preserve childhood for children in Orange County, Calif., and beyond.

Investigational Drug Study Leads to FDA Approval for Fenfluramine in Treatment for Dravet Syndrome

Children who experience seizures associated with Dravet syndrome have a new medication option, thanks to research at CHOC Children’s that helped gain the recent approval of the U.S. Food and Drug Administration (FDA).

Dravet syndrome is a sodium channelopathy that causes an intractable, difficult-to-control form of epilepsy beginning in the first year of life, as well as significant developmental and motor impairments. Many patients with this rare and severe type of epilepsy experience prolonged and unrelenting seizures and are at risk for SUDEP (sudden unexpected death in epilepsy).

Dravet syndrome is difficult to treat with the antiepileptic medications currently available in the United States, but the FDA has recently approved FINTEPLA® (fenfluramine) for the treatment of seizures associated with Dravet syndrome in patients 2 years of age and older. Dr. Mary Zupanc, pediatric epileptologist and co-medical director of the CHOC Children’s Neuroscience Institute, was a key investigator in one of the two international drug studies that led to U.S. FDA approval.

Dr. Mary Zupanc
Dr. Mary Zupanc, pediatric epileptologist and co-medical director of the CHOC Children’s
Neuroscience Institute

“The drug we recently trialed, fenfluramine, showed a significant reduction in convulsive seizures and overall seizures, which helped improve the quality of life not only for patients with Dravet but for their families as well,” Dr. Zupanc said.

Study 1 trialed 0.2 mg/kg/day or 0.7 mg/kg/day. The patients on the higher dose had a 70% reduction relative to placebo in monthly convulsive seizure frequency. And 70% of the patients on the higher dose had at least a 50% reduction in their monthly convulsive seizures compared to 7.7% of patients on placebo. Patients on the lower dose of fenfluramine had a 31.7% reduction relative to placebo in monthly convulsive seizure frequency, and 34.2% of patients on the lower dose had at least a 50% reduction in their monthly convulsive seizures.

In addition to reducing the monthly convulsive seizure frequency in patients whose seizures were not adequately controlled on one or more antiepileptic drugs, most study patients responded to treatment with fenfluramine within three to four weeks, and the effects remained consistent over the treatment period. Dr. Zupanc remarked that fenfluramine’s effectiveness could be “life-changing” for patients with Dravet.

Fenfluramine — used on its own and also paired with phentermine in the popular weight-loss combination known as “fen-phen” — was withdrawn from the U.S. market in 1997 after reports of heart valve disease and continued findings of pulmonary hypertension. Due to these risks, subjects received frequent EKGs and echocardiograms throughout the investigational trial. No valve disease or hypertension was found, but a decrease in appetite and some observations of a minor increase in irritability were noted.

Dr. Zupanc is optimistic about fenfluramine’s application for Dravet, but advised that it is only part of an overall treatment plan. “If a physician has a patient with Dravet syndrome, I would make sure the patient gets referred to a Level 4 epilepsy program, the highest designation for epilepsy centers,” Dr. Zupanc said. “CHOC is a level 4 epilepsy center, which means we do investigational drug studies, vagus nerve stimulation, epilepsy surgery, ketogenic diet and provide a full-service epilepsy program with six epileptologists with board-certification in epilepsy. Because we have participated in these [investigational] studies, we are on the ground floor and know how to dose these drugs and adjust these medications.”

Our Care and Commitment to Children Has Been Recognized

CHOC Children’s Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the neurology/neurosurgery specialty.

Learn how CHOC’s neuroscience expertise, coordinated care, innovative programs and specialized treatments preserve childhood for children in Orange County, Calif., and beyond.

CHOC makes advancements for neurogenic bladder patients

The Urology Center at CHOC Children’s has implemented and evaluated a bladder pressure and volume diary for patients at risk for increased intravesical pressures.

“Patients dependent on clean intermittent catheterization used ruler-based manometry to measure intravesical pressures before leakage or scheduled drainage at home,” said Dr. Antoine Khoury, chief of pediatric urology. Patients were asked to record measurements while relaxed in a supine position.

Dr. Antoine Khoury, chief of pediatric urology at CHOC Children's
Dr. Antoine Khoury, chief of pediatric urology at CHOC Children’s

Study results

The study included 30 patients ranging in age from 1 to 20, with a mean age of 10.

“Home pressures measured at maximal clean intermittent catheterization volume and mean bladder pressure/volume diary pressures were most reliable in predicting urodynamic pressures greater than 30 cm water (AUC 0.93 and 0.87, respectively). Home pressures measured at maximal clean intermittent catheterization volumes less than 20 cm water were associated with normal bladder pressures (less than 30 cm water) on urodynamics, with a sensitivity of 100% and a specificity of 80%,” said Dr. Khoury.

To view this study in greater detail, click here.

A bladder pressure/volume diary helps patients monitor pressure at home and reduces the need for frequent video urodynamics (VUDS) or urodynamics (UDS). As a complementary tool to urodynamics, it provides early detection for high bladder pressures that have the potential to cause kidney damage and renal failure.

Our care and commitment to children has been recognized

CHOC Children’s Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the urology specialty.

Best Children's Hospitals, U.S. News & World Report, Urology, 2020-21

Learn how CHOC’s urology care, ongoing treatment and surgical interventions preserve childhood for children in Orange County, Calif., and beyond

CHOC pioneers medical home for children with autism

The nationwide prevalence of autism spectrum disorder (ASD) in children is one in 54. Finding the most appropriate care for children with ASD, as well as support and education for their families, can be a challenge — a challenge the Thompson Autism Center at CHOC Children’s seeks to make easier.

Thompson Autism Center: Filling the service gap

The Thompson Autism Center is committed to addressing autism defined core symptoms related to social interaction, repetitive behavior and communication via a medical home approach to reduce unmet healthcare needs.

“While our focus is on early diagnosis of ASDs between the ages of 1 and 6, we are also offering many services for the large percentage of children who have co-occurring medical and mental health disorders associated with autism,” said Dr. J. Thomas Megerian, pediatric neurologist and medical director of the Thompson Autism Center.

Dr. J. Thomas Megerian, pediatric neurologist and medical director of the Thompson Autism Center, examines a patient using a stethoscope
Dr. J. Thomas Megerian, pediatric neurologist and medical director of the Thompson Autism Center (left)

“The center is a place for families to come for most of the specialty care needs for their child. Our goal is to have all of the professionals who care for the child communicate with each other in creating a coordinated treatment plan all in one setting, answering questions that families have about their child’s diagnosis and helping to troubleshoot when they are not receiving needed services. We also have specialists who can partner with our families and their school programs to optimize intervention and educational programming and identify appropriate community resources specific to the needs of the child and their family.”

Medical home three-pronged approach

The multidisciplinary Assessment Program offers a comprehensive assessment with a psychologist-led full day evaluation with physicians, speech-language pathologists and occupational therapists as well as a brief confirmatory assessment that’s physician-led, aimed at reducing wait times when a diagnosis is clear.

The Behavior Program addresses refractory behavioral disabilities in a highly structured, safely managed setting to address children and adolescents presenting with agitation, self-injury or aggression. Evidence-based toilet training interventions are also addressed to support each child’s progression. The Behavior Program also offers consultation services for community behavioral therapy providers when a child’s progress stalls despite ongoing therapy.

The Co-Occurring Conditions Program facilitates multidisciplinary consultations, individual or group therapy, and targeting social skill groups to improve interpersonal relationships.

“We also provide transition services and specialists who work on plans for a child’s transition into adulthood,” Dr. Megerian said. “Our mission includes partnering with local organizations, including legal agencies and schools, to provide patients with integration paths into the community.”

Clinical research center of excellence

The Thompson Autism Center is committed to partnering with public and private institutions and government facilities to investigate innovative diagnostics and novel therapies for ASD. Research is ongoing to develop, study and implement behavioral treatments and programs.

“We’re providing a home for groundbreaking research and clinical trials. We’d like to be able to bring clinical trials to the community so that they have safe options for trying novel therapies,” Dr. Megerian said.

Our care and commitment to children has been recognized

CHOC Children’s Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings, and ranked in the neurology and neurosurgery specialty.

Best Children's Hospitals, U.S. News & World Report, Neurology & Neurosurgery, 2020-21

Learn how CHOC’s neuroscience expertise, coordinated care, innovative programs and specialized treatments preserve childhood for children in Orange County, Calif., and beyond.

Fertility future with testicular cryopreservation

Fertility preservation is now a reality for male pediatric and adolescent/young adult (AYA) patients with cancer or blood disorders.

The Hyundai Cancer Institute at CHOC Children’s is a center of excellence and the only program on the West Coast offering testicular preservation for prepubertal patients unable to bank sperm. Testicular tissue is biopsied and preserved in liquid nitrogen.

“Recent research indicates these biopsies contain stem cells, leading to the possibility of generating sperm in the future,” said Dr. Carol Lin, a pediatric oncologist at the CHOC Hyundai Cancer Institute.

Evidence-based research

CHOC participated in an eight-year study alongside U.S. and Israeli institutions to establish a standardized protocol and centralized process to freeze and collect biopsies.

A CHOC Children's pediatric urologist speaks with an adolescent male patient in an exam room

“In total, 189 patients provided samples. A quarter of each sample was used for research and the rest stored for future use. These patients ranged from ages 5 months to 34, with an average age of about 8,” said Lin.

The study discovered that a centralized process and testicular biopsies from multiple sites was a viable option and could accelerate recruitment. Click here to learn more about the study.

Sharing expertise

CHOC is a member of the Oncofertility Consortium, a group of scientists and providers who are committed to fertility preservation in cancer patients. The consortium studies the science of cryopreservation methods, storage of tissue, in vitro follicle growth and communication between patients and doctors, as well as ethical and legal concerns.

Our care and commitment to children has been recognized

CHOC Children’s Hospital was named one of the nation’s best children’s hospitals by U.S. News & World Report in its 2020-21 Best Children’s Hospitals rankings and ranked in the cancer specialty.

Best Children's Hospitals, U.S. News & World Report, Cancer, 2020-21

Learn how CHOC’s pediatric oncology treatments, expertise and support programs preserve childhood for children in Orange County, Calif., and beyond.