Evaluation of Activation of a NCI National Clinical Trials Network (NCTN) Study S1826 for Hodgkin Lymphoma (HL) at Children's Oncology Group (COG) Institutions
Authors: Castellino Sharon M. , Punnett Angela , Parsons Susan K , DeGroote Nicholas P. , Muehle Sally , Li Hongli , Roth Michael E. , Herrera Alex F. , Friedberg Jonathan W. , Seibel Nita L. , Kelly Kara M. 
Published: February 2021

Background: HL is an adolescent and young adult (AYA) cancer that lacks uniform approaches across medical and pediatric oncology. Differences include risk classification, chemotherapy backbone and use of radiation therapy. Heterogeneity in institutional programs and resources for AYAs adds to the gap in understanding why outcomes for AYA HL differ. In order to expedite equitable access to novel agents for AYA patients by medical and pediatric oncology providers, a NCTN facilitated trial for advanced stage HL was launched. The SWOG-led S1826 trial (NCT03907488), open to patients &gt; 12 years of age, was activated in July 2019. We assessed barriers and facilitators to trial activation at COG institutions for this first in-kind approach.
Methods: A web-based survey was distributed through the COG communications office to institutional principal investigators (PIs) of 216 institutions in North America. To achieve optimal response rates, the survey was distributed in four waves over a 6-week period. Branching logic differentiated questions for institutions that had opened or planned to open the trial vs. those who did not. Topics included institutional characteristics, joint partnership with medical oncologists to activate AYA trials, and specific barriers for opening this trial. Descriptive statistics were calculated using SAS v.7.1.
Results: The response rate was 73% with 158 unique responses among 216 COG institutions queried. Among responding institutions 24% were freestanding children's hospitals; 18% were NCI-designated cancer centers. 55% of respondents indicated a known affiliation with another NCTN cooperative group other than COG. 31% indicated prior experience in participating in a non-COG led NCTN trial for other diseases. 42% of institutions reported a central trials infrastructure for joint pediatric and medical oncology trials. 44% indicated use of the central IRB mechanism, and 4% used a provincial IRB. While 40% had an established AYA oncology program, 30% reported regular lymphoma tumor boards with medical oncology; 8% indicated the ability to see AYA lymphoma patients in a joint pediatric and medical oncology clinic.
The trial is open at 79/158 (50%) COG institutions to date and an additional 56 indicated future intent to open the trial. Among 135 COG institutions with open or intent-to-open status, 73% of institutional principal investigator (PI) were pediatric oncologists, 24% were medical oncologists and 4% were joint PIs. PI determination was based on: enrolling as a COG-only site (57%); institutional policy (5%); a discussion among investigators (23%); or other factors (14%). These were categorized as: more resources or anticipated patients in medical oncology (n=4); the trial being opened in medical oncology before pediatrics (n=11); being open in pediatrics before medical oncology (n=2); no interface for joint studies (n=1).
Among the 14% of respondents who indicated the trial would not be opened, a competing trial was the reason in 35%. Other reasons included: lack of awareness of the trial, concerns about study design or chemotherapy backbone, lack of easily accessible protocol documents, anticipated lack of accrual, concerns around funding support, challenges with regulatory support, data management, or institutional process for medical and pediatric joint trials.
Respondents' recommendations for facilitating activation of AYA intergroup studies include needs for: increased resources and funding; guidance on communication and navigation with medical oncologists for managing joint trials; institutional infrastructure for AYA trials; clearer rationale for a change in the chemotherapy backbone relative to prior COG studies; accessibility and consistency of protocol study naming conventions and protocol documents (i.e. therapy roadmap) on the COG electronic site.
Conclusions: Successful implementation of AYA trials is germane to early access to novel agents for younger adolescents. Overall, COG institutions indicate a high level of endorsement for a NCTN AYA trial for HL with 85% indicating activation completed or planned. This survey suggests that AYA trials can be implemented successfully in a network but require education, early communication between pediatric and medical oncologists, and flexible infrastructure for all group participants.
(Funding: U10CA180886, U10CA180888, and UG1CA233230)

Disclosures
Parsons: Seattle Genetics: Consultancy. Herrera:Bristol Myers Squibb: Consultancy, Other: Travel, Accomodations, Expenses, Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Immune Design: Research Funding; AstraZeneca: Research Funding; Karyopharm: Consultancy; Pharmacyclics: Research Funding. Friedberg:Acerta Pharma - A member of the AstraZeneca Group, Bayer HealthCare Pharmaceuticals.: Other; Astellas: Consultancy; Kite Pharmaceuticals: Research Funding; Bayer: Consultancy; Seattle Genetics: Research Funding; Roche: Other: Travel expenses; Portola Pharmaceuticals: Consultancy.