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Now that the RACE for Children Act has come into effect, the drug development industry and patients and their families are optimistic—more drugs will come through the pipeline for childhood cancers. Despite advancements in oncology treatment in recent years, novel drug therapies for children have been lacking due to exemptions to existing legislation. The RACE for Children Act has eliminated these exemptions.

Key Highlights

Our pediatrics experts explore the unmet needs of pediatric oncology trials and how those needs will be met in the wake of the RACE Act.

Nick Tate
Nick Tate

In light of Childhood Cancer Awareness Month, we spoke with the following experts about the unmet needs of pediatric oncology trials and what future development looks like in this space.

This article was written in collaboration with the following experts:

  • Joanna Perkins, MD, MS, Senior Medical Director, Medical Affairs, Hematology-Oncology
  • Missy Hansen, MSN, APRN, CNP-Pediatrics, Pediatric Strategy Liaison, Center for Pediatric Clinical Development
  • Jacqui Whiteway, PhD, Senior Pediatric Strategy Liaison, Center for Pediatric Clinical Development

What are some of the biggest challenges the industry faces when it comes to children's cancers? What can PRA do to help combat these challenges?

MH: One challenge that the drug development industry faces is that, due to the rarity of pediatric cancer, very few sponsors have experience running pediatric trials.

JP: Relative to adult cancers, pediatric cancers are very rare. Therefore, they historically get significantly less attention and prioritization when it comes to the development of clinical trials and how much research funding is directed to pediatric cancers compared with adults.

JW: Up until this point, when pediatric trials were done, they were often run through consortia or academia that are very knowledgeable and experienced in running these trials. With the implementation of RACE Act we expect more trials, and more complex trials, yet the number of pediatric cancer patients will not proportionally increase. Organizations like PRA can help sponsors navigate this complex landscape, including working with pediatric consortia.

MH: In the wake of the RACE Act, there are many companies who are unfamiliar with this very specific oncology landscape. PRA’s experience working with pediatric oncology trials will help position our partners to meet the requirements of the act.

Learn more about our expertise with the RACE Act.

JW: Sponsor unfamiliarity stems from childhood cancer being rare; companies naturally don’t have much experience in this area. On the flip side of that, the investigators and the childhood cancer clinical research sites are very experienced. Unlike some therapeutic areas, where you have to sell sites on trials or as for some rare indications have to consider training for research naïve sites, that’s not an issue here. Investigators are research experienced and seek out trials for initial treatment therapies, as well as relapsed and refractory treatments.

How has clinical research improved outcomes for pediatric cancer patients?

JP: Historically, the overall cure rate for childhood cancer in higher-income countries was approximately 20%. Today, that cure rate has increased to approximately 80%. Certain types of childhood cancer, like low risk B-lineage acute lymphoblastic leukemia, are associated with long-term cure rates as high as 90-95%. Those advancements are remarkable—the leading reason for those advancements is clinical trials.

Because childhood cancer is so rare, in the 1960s, researchers and clinicians decided they wouldn’t be successful at curing these diseases by working alone in silos. That kickstarted the era of childhood cancer consortia. In the US, this ultimately led to the development of the Children's Oncology Group, which is one of the largest consortia in the world overseeing the treatment of childhood cancers.

Of course, there are other technological advancements, such as improvements in combination chemotherapy regimens, improvements in radiation techniques, and the development of immune mediated cancer therapies like monoclonal antibodies, as well as molecularly-targeted agents.

See what our experts said about blood cancers, their treatments, and how they affect populations differently.

How have pediatric oncology treatment options advanced? Are there any specific cancers that need more research?

JP: All childhood cancers need more research. No childhood cancer has a 100% cure rate. Until there is a 100% cure rate for these diseases, there needs to be more research. There are certain childhood cancers, such as B-lineage acute lymphoblastic leukemia and low-stage Wilms tumor, that have cure rates in excess of 90%, but even that’s not good enough.

MH: Some of the most highly aggressive brain tumors, like diffuse intrinsic pontine glioma (DIPG) and high-grade glial tumors (glioblastoma), have extremely poor overall survival rates with life expectancy about 12-18 months. We don't have any standard therapy for either that providers can offer other than radiation, and that is typically only to prolong life. One thing that contributes to the poor survival rate of patients with DIPG is that it is impossible to obtain a complete resection of the tumor, which is a qualifier for improved life expectancy for any solid tumor. Due to its growth in the brain stem which controls our heart rate, blood pressure and breathing, complete resection of the tumor impossible. Also, tumors like glioblastoma are highly aggressive and invasive on the many grooves and crevices of the brain. Those tumors are highly resistant to many of our available therapies.

As I said previously, one of the most important factors to overall survival is the ability to completely resect the tumor and for there to be no metastatic disease. Surgical intervention is key and there have been improvements in our ability to completely resect, without damaging vital, healthy brain. One example is the use of intraoperative MRI, which allows the neurosurgeon to not only visually assess the progression of tumor resection, but also to have the patient's tumor area scanned intraoperatively to help confirm that complete resection was obtained. Another success in certain types of brain tumors is the use of laser or LITT (laser interstitial thermal therapy), which is a probe that, once properly in position inside the brain tumor, can emit pulses of heat to kill the surrounding tumors cell. If appropriate for a patient, LITT can be more therapeutic while being less invasive allowing for quicker recovery.

JP: As an example of the impact of metastatic disease, many bone and soft tissue sarcomas, which often occur in teenagers and young adults, have cure rates up to 70-80% when they're localized. However, when those diseases are metastatic, at time of initial presentation or at time of relapse, the cure rate is only approximately 20%-30%. That speaks to the need to improve on our therapies for metastatic cancers, as well as to constantly improve upon our detection methods to detect cancers at an earlier stage. As Missy said, part of the underlying principle of treatment is if you can remove the tumor in its entirety before it spreads to other parts of the body, you have a much better chance of achieving a cure.

MH: Shifting focus slightly to a world health perspective, if you look at lower-income countries, children diagnosed with cancer have an overall approximately 20% survival rate. This differs compared to high income countries, where it is approximately 80%, as Joanna said earlier. The sad truth is that if they had been born in a higher income country they quite possibly could have survived their disease. Some of that is related to difficulty in early diagnosis, which is less of an issue in many countries like the US. It’s paramount to make these survival rates more uniform worldwide.

JP: When children with cancer present to a health care facility in lower-income countries, they’re often diagnosed at a later-stage, thus leading to a poorer prognosis. This is often due to the barriers these families face in getting to a pediatric cancer center. Barriers such as distance, travel means, cost and time away from other responsibilities are accentuated in low income countries.

What role does virtual care play in pediatric cancer treatment?

JP: In the face of COVID-19, the ability to provide in-person care has definitely impacted pediatric cancer treatment, just like every other field in medicine right now. Historically, at pediatric cancer centers, children would be seen in person for most visits, whether it was for a physical exam and blood count checkup, a chemotherapy infusion, or hospital admission.

Now, centers have been forced to modify the approach to care. Many sites are restricting in-person visits to only those absolutely necessary, like for a chemotherapy infusion that can't be given at home. Other visits, like lab work or follow-up assessments, are being conducted more frequently at home by using resources like home health care and telemedicine.

One challenge to virtual care is that many sites simply don’t have the technology. The pediatric cancer center might have the technology, but the surrounding smaller clinics and hospitals, as well as the patients and families, may not. There is also the challenge of there being multiple systems and the inability to link or communicate with each other.

MH: When we evaluate the impact of virtual care, there are many things to think about: What is the feedback from these families? Did it impact the patient in a positive or negative way? Did they appreciate having more occasional local lab visits or did they miss going in person and seeing their oncology team? Did they still do well with their overall treatment? What time points were missed or what was impacted? All of those questions and answers will need to be considered. It will take time to figure out the entire COVID-19 virtual impact on many treatment areas including pediatric oncology.

JW: It’ll be interesting to get feedback from patients and families about their point of view.

Oncologists are busy. They now must schedule these consultations and office visits virtually, while still managing patients that need to be seen in the clinic. That back and forth between virtual and on site may be more difficult to manage. For the patient and family, there may be some aspects to virtual care that could be seen as positive for the family, as it is more flexible. For example, they would not have to spend as much travel time, accommodate siblings, or miss school time for the patient.

JP: How the virtual and on-site visits are managed is variable between institutions and even within the same institution. Also crucial to consider is that in this time of COVID-19, many health care institutions are limiting staff, which leads to less people on site to help with the flow of patient care and other responsibilities. Hospital systems have had several months now to evaluate the pros and cons of virtual medicine within the context of a global pandemic. It is the hope that the lessons learned will be associated with improvement in many aspects of health care.

Learn how PRA’s Mobile Health Platform supports pediatric cancer trials for centers that don't have their own telemedicine platform.

What steps are taken to ensure a child understands their diagnosis? How do pediatric cancer patients cope with their diagnosis, and what strategies can be used to further aid them?

JP: There's wide variability in understanding a pediatric cancer diagnosis, depending on the age and cognitive abilities of the child. Those who are pediatric-trained have skills to be able to communicate with children of all ages. We know how to speak in terms that they understand and that help minimize their fear.

Typically, when the initial diagnosis is presented, and depending on age or developmental stage of the child, the conversation begins with the parents or legal guardian. Then, working with the parents, a best plan to approach the child with the diagnosis, treatment plan, and expectations is developed. Many pediatric cancer institutions have dedicated supportive care services, including child life specialists, psychologists and social workers, all specialized in pediatric cancer. These care team members generally meet routinely with all patients. Child Life and Psychology proactively follow up with the kids on a periodic basis, which is tailored to the child’s needs. They don’t wait for the children to demonstrate that they are suffering or struggling with coping.

MH: There are also great resources through various services and organizations that provide age-appropriate print materials to help children understand their diagnosis. JUMO is an excellent child-friendly resource that includes standardized materials or materials tailored to the specific trial needs.

JP: Many centers also have supportive events throughout the year. For example, there are summer camps for children going through cancer treatment. These camps allow them some normalcy and the ability to do things that they did prior to their diagnosis of cancer. They get to spend time with other kids that understand what they're going through.

MH: Some pediatric cancer centers also treat older adolescents and young adults, as research shows better outcomes for patients with certain disease if they are treated at pediatric cancer centers. These centers also have dedicated programming, support groups, and in-hospital spaces dedicated to these older patients. Those ancillary supportive services are vital for children and young adults going through cancer therapy to experience some sense of normalcy, as much as possible.

Given the number of organizations and research organizations dedicated to fighting childhood cancer, why does the public not understand the prevalence of pediatric cancers?

JP: Incidence plays a major role, and often contributes to an underlying lack of awareness. If you talk to a typical 50-year-old for example, they probably know several people who are going through, or who have gone through, some type of cancer treatment. It's much less likely they have a child in their lives who is going through cancer treatment.

MH: To further highlight that, higher numbers of patients lead to a greater return on investment, so there's more pressure on funding organizations to prioritize adult research. There are organizations that are trying to address this disparity. For example, Leukemia & Lymphoma Society (LLS) recently dramatically increased the amount of funding dedicated to pediatric cancer trials. PRA is partnering with LLS on a global precision medicine clinical trial for children with relapsed acute leukemias, dubbed the PedAL trial.

Learn more about LLS PedAL here.

Addressing the clinical needs of children based only on what works in adults is no longer acceptable. Our Center for Pediatric Clinical Development has unparalleled pediatric expertise built on a foundation of analytics, partnerships, and experience. We help our clients save time and resources by determining the feasibility and effectiveness of pediatric studies at every phase of a program. Our global experience allows us to develop and execute country-specific, customized recruitment and retention initiatives to help study teams meet or exceed goals.

Learn more about PRA's Center for Pediatric Clinical Development

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