Even in COVID-19 World, Children’s Oncology Group Tackles Unmet Needs in Sarcomas

The Children’s Oncology Group (COG), an organization dedicated to pediatric and adolescent cancer research, continues to evolve with ongoing and innovative research efforts in the midst of the coronavirus disease 2019 (COVID-19) pandemic, explained R. Lor Randall, MD.

Additionally, the group has expanded its offerings to include the Adolescent and Young Adult (AYA) Responsible Investigators Network, in an effort to increase AYA enrollment onto COG trials.

“COG is fully operational in the virtual medium and is really making headway on children and young adult cancers,” said Lor R. Randall, MD, the David Linn Endowed Chair for Orthopaedic Surgery, as well as professor and chair of the Department of Orthopaedic Surgery at the University of California, Davis Health.

In an interview with OncLive, Randall highlighted the innovative efforts by the COG, ongoing studies in sarcomas, and how the organization is adapting during a world with COVID-19.

OncLive: What is the foundation of COG? How would you best describe its mission?

Randall: The COG is very much like all of the cooperative groups; it is a conglomeration of pediatric oncologists and allied oncologists, and it is dedicated, in this case, to developing clinical trials across all institutions to treating kids with cancer. COG was a merger of the Pediatric Oncology Group and the Children's Oncology Group, many years ago, and it is really the world’s leading authority in children's cancer.

The COG’sFall 2020 Group Meeting took place in mid-September. What did this year’s event look like given the COVID-19 pandemic?

It was a virtual format. [The organization] did a fantastic job, especially for those of us who are a little less technologically savvy—they were able to coordinate breakout rooms and all of those sorts of things. We kept the format that we have kept in the real world, if you will, but we made it virtual. Many of the presenters prerecorded presentations, and then for those of us who moderated sessions, the technician in the breakout room would play their presentation. Then, in real time, the moderator would do a Q/A, which was well done considering [the global pandemic]. I came away from it pretty impressed and pretty optimistic that, if we don’t get back to normalcy in the next year, we'll still be OK in terms of productivity in healthcare via virtual formats.

What was your role at this year's meeting?

I work on 2 committees. My official capacity is on the COG’s Bone Tumor Committee; there is also a Soft Tissue Sarcoma Committee, of which I am a member, but I don’t have a leadership position in. For the Bone Tumor Committee, I am in charge of the local control sessions; we have a variety of studies that are being developed that are usually drug-based, and there is potentially a local control question. We then take that part of the study, where the local control part of the question is relevant, and break that into its own session —to talk about local control.

Now, what is important to point out here, is when I refer to local control, historically, that has typically meant the primary tumor. If you’re talking about, for example, bone osteosarcoma, and local control you immediately think about getting the osteosarcoma out—the primary mediastinum femur. But in this case, local control has morphed a little bit and is also involved in the local control of metastatic disease.

In the trial led by John Doski, MD, [investigators are] looking at open versus thoracoscopic management of metastatic lesions in osteosarcoma. That study is still in the final throes of development, but it is setting up a paradigm now by which were not just focusing on the local control of the primary, but we are also talking about the local control of the metastatic lesions.

Another study is in development where patients who have metastatic disease are going to have mastectomies in the lung where they will receive stereotactic body radiation therapy (SBRT) and an immune checkpoint inhibitor. The patient gets SBRT to a single nodule and they will get an immune checkpoint inhibitor, and then when those lesions come out, the nodule that underwent SBRT will be compared with the lesions who did not get SBRT to see if the radiation stimulated the immune response to the immune checkpoint inhibitor. We know, from other trials, that radiotherapy is used to boost the response to immune checkpoint inhibitors.

It’s those sorts of things coming to the [area of] local control, which are very exciting to us; these things are more procedurally based in our cancer care.

What were the reactions or feedback from those who attended this meeting?

[There was] a lot of excitement. There is still the tenacity needed to get some of these [ideas] to the starting line. We always talk about getting to the finish line, but what we’re trying to do is get these [research ideas and efforts] to the starting line. The conversations have a healthy degree of skepticism; it is always hard to randomize procedural cases. It’s hard enough to think about a therapeutic pill versus a sugar pill, but now, if you’re talking about one procedure versus another, which is invasive in nature, your “Danger, Will Robinson!” sort of response comes online.

Therefore, once this study, the osteosarcoma mastectomy study comes online, we are still going to have concerns about enrollment and [patients] willing to go on one arm versus the other.

What are the eligibility criteria for this osteosarcoma study?

It comprises patients who present with oligometastatic disease and includes adults. They receive methotrexate, cisplatin, and doxorubicin chemotherapy. Then, they go to randomization for either a thoracoscopic versus open procedure. The tailwinds of that study, that I have alluded to with the immune checkpoint inhibitor study, is that these other studies are going to come online.

What other information from the COG is imperative to highlight?

The COG is now partnering with SWOG, ALLIANCE, Canadian Cancer Trials Group, NRG, and ECOG, through the National Clinical Trials Network (NCTN) mechanism, to try to build out some of these clinical trials.

[The AYA Responsible Investigators Network] is an effort that Lisa Kopp, DO is in charge of; this is a NCTN SARC [Sarcoma Alliance for Research through Collaboration] AYA Sarcoma Clinical Trials Working Group and they meet monthly. They are trying to meet monthly to try to hammer away at the activation and energy to get AYA trials [up] across cooperative groups.

This committee is also looking at enrollment barriers for a study titled ARST1321. This was a pazopanib (Votrient) study in soft tissue sarcomas, and [there is an ongoing] post-analysis to find out why on the enrollment arms, there was difficulty getting patients on the non-chemotherapy arm. Patients were willing to enroll on the chemotherapy arm, where there was a randomization for the drug, but there was also an option for [patients to receive] radiation/non-chemotherapy—and patients were not willing to do it. We are going through all of the sites, centers, and all of the patients who chose not to enroll [on that arm] and [determine] why that happened.

Reference

1. Roth M, Mittal N, Saha A, Freyer DR. The Children's Oncology Group Adolescent and Young Adult Responsible Investigator Network: a new model for addressing site-level factors impacting clinical trial enrollment. J Adolesc Young Adult Oncol. 2020;9(4):522-527. doi:10.1089/jayao.2019.0139