During the next few years, St. Jude will greatly increase the number of children treated worldwide on its clinical trials. It’s a goal that demands ORGANIZATION. LEADERSHIP. EXPERIENCE. DEDICATION. Qualities already honed in trials like SJMB12.
When Jayde Gordon emerged from an MRI in September of 2014 and glimpsed her mom’s tear-stained face, the 9-year-old grabbed her stuffed monkey and held on for dear life.
“I was really scared,” Jayde recalls. Her fear intensified when she learned she had a brain tumor. “I started crying because I didn’t want to die.”
Early the next morning, Jayde was whisked into surgery, where doctors removed an orange-sized mass. She had medulloblastoma, the most common malignant brain tumor in children.
The little girl soon embarked on six weeks of radiation therapy and four rounds of chemotherapy as part of a clinical trial at St. Jude Children’s Research Hospital. Hundreds of researchers, clinicians and other professionals had toiled for years to create this study, which is helping to find new treatments for young patients with medulloblastoma.
The St. Jude clinical trial in which Jayde enrolled is headed by Amar Gajjar, MD, director of St. Jude Neuro-Oncology, and Giles Robinson, MD, of St. Jude Neuro-Oncology. That study, known as SJMB12, is offered at St. Jude and 20 collaborating centers spread from the U.S. and Canada to Australia and New Zealand.
By including other institutions in studies such as SJMB12, St. Jude can gather data more quickly and accelerate progress toward cures.
During the next six years, St. Jude plans to double the number of non-St. Jude patients enrolled in collaborative studies such as this one. What is involved in creating such a project? Years of research. Mountains of paperwork. Teams of dedicated professionals united by a common goal.
It’s an undertaking of mammoth proportions—but for the scientists, staff and families involved, it’s well worth the effort.
We are using this combined approach to assess risk—a first in North America—to match patients with the radiation dose, chemotherapy agents or novel therapies targeting specific subtypes that we believe offers the best hope for long, rewarding lives.
Subtypes and survival
When Jayde was born in March of 2005, St. Jude scientists were already conducting research that would one day help save her life. Researchers soon proved that medulloblastoma was not one disease—as scientists had always assumed—but had four distinct subtypes caused by specific genetic mutations. Those subtypes are named sonic hedgehog (SHH), wingless (WNT), Group 3 and Group 4. Survival rates vary widely from one subtype to another.
“In the past, some patients did very well and some did poorly—and we didn’t know why,” Gajjar says. “Subtypes help explain why cure rates varied so widely.”
Children with medulloblastoma once received one-size-fits-all treatment. But now therapy could be based partially on subtype. Children with the WNT subtype, such as Jayde, might be cured with less-intensive treatment, allowing them to avoid many of the long-term side effects that plagued earlier generations of patients. Kids with more aggressive subtypes could receive more intensive treatment, increasing their chances for cures.
Armed with these new findings, scientists and clinicians teamed up to create a sophisticated clinical trial, named SJMB12. This study would take into account the subtype as well as other factors, such as whether the tumor could be surgically removed, what the tumor looked like under the microscope, and whether the cancer had spread to other parts of the brain and spinal cord.
“We are using this combined approach to assess risk—a first in North America—to match patients with the radiation dose, chemotherapy agents or novel therapies targeting specific subtypes that we believe offers the best hope for long, rewarding lives,” Gajjar says.
From lab to clinic
Many research studies fed into the SJMB12 clinical trial. For instance, Robinson and his colleagues discovered that a targeted therapy used to treat skin cancer was also effective against the SHH subtype of medulloblastoma in adults. Now St. Jude patients with the SHH subtype receive that medication as part of treatment.
“This is the first targeted therapy for medulloblastoma,” Robinson explains. “Targeted therapy is potentially very exciting because, as the name implies, it’s hitting a specific target. It may have less toxicity than previous treatments.”
Martine Roussel, PhD, of St. Jude Tumor Cell Biology, worked with Anang Shelat, PhD, of St. Jude Chemical Biology and Therapeutics, to pinpoint two other drugs that were ultimately featured in SJMB12. And Clinton Stewart, PharmD, of St. Jude Pharmaceutical Sciences, led experiments to determine the exact doses of drugs to use in the clinical trial. (See related story in summer 2014 Promise.)
Targeted therapy is potentially very exciting because, as the name implies, it’s hitting a specific target. It may have less toxicity than previous treatments.
Marshaling the troops
An army of doctors, researchers, nurses, project managers and other staff members helped write the clinical trial, negotiate the use of drugs used in the study and manage the thousands of details that accompany a project of this magnitude.
An internal scientific review committee, the St. Jude Institutional Review Board, and industry and government agencies weighed in to ensure the trial was scientifically sound and met safety regulations. Teams of St. Jude staff created the study’s infrastructure, which included building an electronic database and entering orders into the electronic medical record.
For an international clinical trial like SJMB12, St. Jude employees carefully select collaborating sites. They visit each location in person to ensure that the institutions have the experience required to run a sophisticated study, have access to electronic medical records, possess essential equipment and facilities, and can provide top-notch clinical care. Throughout the trial, St. Jude employees work closely with the collaborating centers to ensure that the trial proceeds smoothly.
Because medulloblastoma affects a relatively small number of children worldwide, progress is accelerated when institutions work together.
“The more sites you have, the faster you can complete your trial,” explains Mary Griffin of St. Jude Neuro-Oncology. “A multi-institutional trial like SJMB12 requires a lot of time and effort to develop. But it allows St. Jude to expedite enrollment and it allows the other facilities to offer this therapy to patients in their areas.
“It’s a huge operation,” Griffin continues, “involving more than 100 people at St. Jude. From initial concept to enrolling the first patient can take about a year and a half. We’re working to compress our timeline for future studies.”
A global consortium
The infrastructure and expertise used in St. Jude collaborative trials such as SJMB12 will soon be expanded and enhanced as the hospital invites a dozen of the world’s top pediatric programs to help develop similarly complex clinical trials for some of the toughest cancers.
“For some childhood cancers, each institution might see only a couple of cases a year,” observes James R. Downing, MD, St. Jude president and chief executive officer. “Individually, nobody can make much progress. But if St. Jude leads a consortium of institutions to design these protocols and run them, we can make the kind of progress that nobody has been able to make before.”
Building on success
Jayde Gordon is the walking, talking, dancing beneficiary of St. Jude research and clinical care. Because she had the WNT subtype of medulloblastoma, she received reduced doses of chemotherapy and radiation therapy. Even so, the treatment was challenging.
“Chemo is the worst,” she proclaims. “It was not fun.”
Now 11 years old, Jayde returns to St. Jude for checkups every three months. She and her mom say it’s like going home.
“St. Jude is family now and always will be,” says Jayde’s mother, Kristy Pelt. “You cannot find a more loving and compassionate and caring staff. And the fact that it’s a research hospital is so important to us.”
Kristy knows the research conducted at St. Jude helped save her daughter’s life. And Jayde’s participation in SJMB12 will help doctors create even better treatments for children worldwide.
“I know I didn’t coin the phrase,” Kristy says, “but St. Jude is the best place you never want to be.”