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Funding, regulatory issues hindering clinical trials in young patients with cancer
Enrollment in clinical trials routinely offered to pediatric cancer patients; adolescents, young adults do not have enough trials available.
Enrollment in clinical trials is a standard approach for the care of children with cancer, but a lack of funding may be detrimental to the development of new treatments for this population.
Pediatric clinical trials have historically accrued a larger percentage of patients than adult clinical trials. Approximately 3% of adult patients with cancer are enrolled in trials, whereas an average of 60% of children with cancer are enrolled in clinical trials.
The field of pediatric oncology is based in research. According to Peter Adamson, MD, chief of the division of clinical pharmacology and director of the office of clinical and translational research at the Children’s Hospital of Philadelphia, clinicians in the late 1950s realized that because of the rarity of childhood cancers, collaboration was necessary to make progress.
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“All people trained in the field of pediatric oncology train in a culture of clinical research,” Adamson said in an interview. “For many decades, research has been a central part of pediatric oncology care.”
Because it is a multimodality specialty, pediatric oncology is most often practiced in large academic medical centers rather than private practices; therefore, clinical trial enrollment in this population is common. If there is a clinical trial open and a patient is eligible, enrollment into the trial is often the first treatment option.
“Some people have commented that the standard of care for childhood cancer is being enrolled in a clinical trial, and that isn’t necessarily stretching the truth,” Gregory Reaman, MD, professor of pediatrics at the The George Washington University School of Medicine in Washington and chair of the Children’s Oncology Group, said in an interview.
“Clinical trials are experiments and research that define the standard of care. As such, they cannot really be called the standard of care. However, since it is so widespread and uniform that eligible children are enrolled in trials, it almost seems to represent the standard,” Reaman said.
Trial accrual
Until about 2000, accrual to childhood cancer clinical trials was at least 60% of all children diagnosed with cancer in the United States, according to Archie Bleyer, MD, medical advisor to the cancer treatment center at St. Charles Medical Center in Bend, Ore. Most children were accrued at diagnosis. Some children were accrued to two trials such as a clinical trial and another biological or an epidemiological trial. Among children whose cancer recurred, many entered a trial.
Since 2000, accrual has declined to less than 50%. In 2000, the Children’s Oncology Group was created when four separate groups merged with a goal to continue raising the accrual rate to clinical trials. Instead, the opposite has apparently happened, Bleyer said.
“With the clinical trial funding limitations that have occurred, it could be worse. But it is lower than what I expected. We seem to have reached a plateau in reducing the survival and mortality rates for childhood cancers,” Bleyer said in an interview.
Aside from funding, Bleyer said there are also regulatory issues inhibiting the availability of clinical trials, such as difficulty getting protocols approved by review boards, both locally and nationally. Bleyer also said that the Children’s Oncology Group is still working through some operational issues resulting from the merger in 2000 that affect the facilitation of clinical trials.
Overall, the main issues are funding and improving enrollment in clinical trials for adolescents and young adults.
Rare and young adult cancers
In some cancers, there is continued progress, Bleyer said. The cancers that have maintained a high clinical trial accrual rate are the ones that continue to make progress.
As children age, the chance of being enrolled in a clinical trial plummets from more than 50% to less than 2% by the time the adolescent is 18 to 20 years old, according to Bleyer.
“There are proportionately more infants enrolled in clinical trials than there are young adults, but there are more young adults with cancer than there are infants,” Bleyer said.
Leukemia is the most common cancer in children, so there are a large number of related studies but there are also studies for less common cancers, such as osteosarcoma, according to Reaman. The disparities in clinical trials occur not necessarily because of diagnosis, but because of the age group in which particular tumors are more common, Reaman said. Leukemia is more prevalent in children aged 2 to 5, whereas less common tumors are seen more frequently in adolescents and young adults.
“Accruals to clinical trials for adolescents and young adults are not nearly as high as they are for young children,” Reaman said. “There are many social, psychosocial and socioeconomic issues that affect the low accrual into clinical trials for this population.”
One possible reason is that many of these patients are treated in private practices or community medical centers where clinical trial enrollment is not available. Another reason is that some of these patients may not have adequate health insurance coverage for enrollment in a clinical trial.
“We take insurance away from children and adolescents as they age,” Bleyer said. “If half the country does not have steady insurance, we have a problem getting the patient to a place that has clinical trials available.”
For any cancer, there needs to be clinical trial evidence, but that does not necessarily mean a randomized, large, phase-3 clinical trial for every disease, Adamson said.
“There are some diseases where such trials are not going to be feasible,” Adamson said. “But you can still have clinical trials that have data and supporting evidence as to whether a treatment has a beneficial effect.”
Funding concerns
The bulk of pediatric clinical trials are conducted by the Children’s Oncology Group, which is funded by the NCI. According to Reaman, the accrual to clinical trials has been stable. In addition to clinical trials, there are a number of nontherapeutic investigations including correlative biology studies for which enrollment has significantly increased. However, there are some concerns.
“We are hampered by the fact that we have limited resources, which are shrinking on an annual basis due to cutbacks in funding to medical research in general,” Reaman said. “This directly affects what we can do, what we want to do and what we will be able to do.”
The Children’s Oncology Group was forced to make budget cuts due to a lack of funding. Although the group has sought support from the private sector, they have not been very successful, Reaman said.
For most research, the cost of the trials is not entirely covered by federal grants. The result is a large amount of voluntary work and contributions made by individuals involved in the research and contributions made by hospitals and institutions to help offset the infrastructure costs, which are inadequately covered by federal grants.
“The NCI does indeed support clinical research, but the level of funding is insufficient to do all the studies that we need to do,” Adamson said. “We get support, but never enough to accomplish our mission. That, by far, is the number one issue in pediatric clinical trials.” – by Emily Shafer