By Maxine Bookbinder

July 13, 2017 | The Pediatric Neuro-Oncology Consortium (PNOC) and the Children’s Brain Tumor Tissue Consortium (CBTTC) are collaborating on a first-of-its-kind clinical trial that will post de-identified patient data live to the cloud as the trial is underway. The non-profit Dragon Master Foundation is providing partial funding.

The trial is designed to quicken the process of testing new therapies specific to genomic pathways and mutations of pediatric patients with Diffuse Intrinsic Pontine Gliomas (DIPG), brain stem tumors that are usually fatal within a year from diagnosis. Clinicians will use FDA-approved drugs matched to each patient’s deeply-defined tumor molecular characteristics. The trial is set to begin this summer.

The purpose of posting live data, says Adam Resnick, CBTTC and PNOC Scientific Chair, is to give scientists from Philadelphia to Pondicherry the opportunity to access rare, large-scale data they can analyze, integrate into their own data, and then share, accelerating discovery time of a cure. Resnick is an expert in brain tumors, and Director of the Center for Data-Driven Discovery for Biomedicine at Children’s Hospital of Philadelphia (CHOP); CHOP serves as the CBTTC’s coordinating center.

“This effort is unlike anything we’ve been able to do in our clinical trial research history,” says Resnick. “The ultimate conclusion of the trial will hopefully divulge how individual patients respond to specific therapies, in the context of their own tumor specific genomic data.” This is the first time a clinical trial like this will make non-outcome patient data available live in a cloud-based research environment in near real time.

Web of Patients

For PNOCs first full-scale clinical trial, the 15-hospital consortium is focusing on individual patients’ molecular and genomic biology while posting their de-identified data to the cloud for integrative analysis. “Most of these tumors are rare and don’t yet attract the interest of big pharma,” says Resnick. “This trial offers real-time implementation for brain tumor patients that martials the interpretive powers of the genomics community on behalf of patients with limited therapeutic opportunities.”

Data will be stored on CAVATICA, a cloud-based biomedical data analysis platform built by Seven Bridges that allows collaborative access, sharing, and analyzing of pediatric cancer data (see, Lessons Learned From The Cancer Genomics Cloud). CAVATICA, named after the heroine in Charlotte’s Web, has now released 53 datasets for collaborative discovery, from pediatric cancer to congenital heart defects; it is compatible with the Genomic Data Commons and other NIH data repositories. CHOP also brought in data from 1,700 subjects from previous trials. CAVATICA can store both pediatric and adult data, allowing researchers to cross-reference diseases in adults and children.

“CAVATICA gives us unprecedented opportunity to research a number of childhood diseases, ranging from pediatric brain tumors that are the leading cause of disease-related death in children to rare pediatric disorders that get limited attention and resources,” says Resnick. Other physicians with DIPG patients, as well as any researcher and investigator, whether from prestigious academic research centers or small, stand-alone rural clinics, can research cancer data online in real-time for their patients or cross-reference for other forms of tumors and cancers. “CHOP and many other academic institutions have their talented researchers, but we don’t want to keep these discoveries limited and in-house only,” Resnick says.

Genomics data have traditionally been kept within institutions, and adult and pediatric tumors have remained independent of each other. “There wasn’t an open data enterprise,” says Resnick. “Now CAVATICA and its founding research hospitals are dedicated to an acceleration of collaborative discovery empowered by technology. It’s a numbers game. The more data you have and the more people who work on this data, the more likely a discovery is possible.”

Until recently, finding a tumor’s genomic links has been hard due to the limited information on pediatric cancer. Now, CAVATICA users can cross-reference and find connections between multiple rare illnesses and cancers. “Kids don’t get cancer because they smoke or out in the sun. Pediatric cancer occurs in the context of development. And kids with other birth defects and rare diseases have greater risks for cancer and vice versa,” says Resnick. “There is an emergent need for integrative efforts on behalf of kids with illnesses… For our population, the more data made available in real time, the better the chance of finding a discovery.”

Compute credits and public collaborative projects are available through commercial partners, academic sponsorships, and philanthropic and grant support from patients, families, and foundations. However, investigators can process data independently and pay for their own computational time. “We hope that it is used for the benefit of the community and its children,” says Dr. Resnick.

Dragon Masters

But storing, analyzing, and sharing data in real time is a financial and time-consuming commitment. Enter Dragon Master Foundation. Amanda Haddock, Dragon Master Foundation president and co-founder, launched the non-profit in 2013 to encourage researchers to identify patterns through genomic sequencing and to discover new therapies through big data and open data access. She initially contacted several cancer researchers globally who rejected her concepts and criticized her vision. “You couldn’t find out how patients did. With genomic data, you can see why patients do well,” says Haddock.  

Then she approached CBTTC. “CBTTC wanted to share their data and work with data beyond brain cancer and kids. We all have the same, very large vision of what can happen with cancer data.” Dragon Master’s $300,000 donation will fund sequencing for 200 children, computational time, and cloud storage on Amazon Web Services.

“We don’t know where the answers are going to come from,” says Haddock.  “If we limit access to the data, we limit where the answers will come from as well. What if the person who can discover this lives in a small town without access to a large academic facility?”

Haddock’s son, David, died from glioblastoma multiforme in 2012 at age 18, prompting Haddock and her husband to start Dragon Master Foundation to change the way research is conducted. “No one wanted to build [data-sharing platforms] that everyone could use; it was too hard or cost too much money,” Haddock says. “I didn’t want to be part of the generation that didn’t cure cancer because it was inconvenient. I couldn’t sleep at night knowing that this could be the answer and we weren’t doing it. We were uniquely able to understand some of the research, the IT capabilities, and then translate it back to people. We thought we’d give it a shot and see if we could make a difference. “

Dragon Master Foundation has a two-year commitment to this trial. After that, it will focus again on infrastructure and grassroots fundraising, and Haddock will search for another clinical trial “as brave and bold” as the DIPG trial to fund.

Haddock believes there needs to be a change in how research is conducted. “There's a paradigm shift that needs to happen; we’ve been doing the same thing for decades,” she says. “We need to open up data and look at the bigger picture.”

Resnick agrees. “Genomic data is extremely complicated. Currently no one comes up with the same set of analyzed results. We need multiple people to analyze the same data with their own workflows and using multiple data sets to empower discoveries. This is a tremendous opportunity for the scientific community to cross-reference and intersect ideas. We want researchers for melanoma to be able to access data on childhood brain cancer and for childhood cancers to inform discoveries in adult cancers. We want to support the collaborative discovery effort of researchers coming together irrespective of geography or specialty.”