Jett Ramsey may only be 4 years old, but already he’s mastered the yin and yang of emotional balance. Some days he’ll sweetly grab his mom’s cheeks and profess his love for her. Other days, the California boy fights with his two older brothers and peppers his conversation with zingers and wisecracks.
But Jett’s feisty side has been particularly useful during the past year in helping him weather rigorous treatment for medulloblastoma, the most common brain cancer in children. And when his tumor came back despite surgery, radiation and chemotherapy, Jett’s grit was again called to the mat.
He is part of an international clinical trial led by St. Jude that aims to increase the arsenal of treatments against the disease. The study, called SJELIOT, is testing a new chemo drug called prexasertib. The drug prevents medulloblastoma cells from repairing themselves after damage caused by other chemotherapies. Researchers hope this medication will strengthen the blow to cancerous cells when used with mainstay treatments.
“My husband and I feel this trial is the best option for Jett because it provides the most hope,” says Jett’s mom, Amy Ramsey. “It also allows Jett to be normal. He’s happy, he doesn’t feel sick, and he seems like a normal kid right now. That’s huge.”
SJELIOT aims to enroll about 100 patients whose medulloblastoma tumors didn’t get better with treatment or came back afterward.
About 350 children and adolescents are diagnosed with medulloblastoma in the U.S. each year. More than a decade ago, St. Jude researchers led research that showed medulloblastoma is not just one disease, but has four distinct subtypes caused by specific genetic mutations. Those subtypes are named wingless (WNT), sonic hedgehog (SHH), Group 3, and Group 4. Survival rates vary widely from one subtype to another. About 95% of children in the WNT subgroup enjoy long-term survival, compared to about 50% of patients in Group 3. Overall, about 70% of patients survive beyond five years.
Hoping to attain the higher treatment success rates of the WNT subtype, St. Jude researchers led a variety of studies in recent years to increase treatment options and reduce side effects. SJELIOT will include children with more aggressive subtypes, like Jett’s.
“The thing to know about medulloblastoma therapy is we have a good foundational therapy on which to build,” says St. Jude oncologist Giles Robinson, MD, who leads SJELIOT. “This foundation cures many but not all, and it produces some unwanted side effects.
“What we’re trying to do at St. Jude is take that standard therapy and make it better,” he continues, “whether by reducing some of the treatments that cause toxicities or by creating more innovative and, hopefully, better additions to therapy— such as that of SJELIOT— to give to a patient who’s more likely to relapse.”
Chain of Success
SJELIOT was several years in the making. It launched after an Australian researcher identified prexasertib as a test-worthy medication against medulloblastoma. More research performed globally by St. Jude and other collaborators found the drug to be potent against aggressive subtypes of medulloblastoma cells. The trial includes children at St. Jude and nine other centers in Australia and Germany.
Before a patient can take part in the study, pathologists determine which subtype of tumor the child has. Patients whose tumors are Group 3, Group 4, SHH or an undetermined type can be included.
“The positive results we saw, along with other preclinical work, suggested that all recurrent medulloblastomas could benefit from this therapy,” Robinson explains.
“You don’t ever want somebody to relapse or recur with disease,” he adds. “You want to get it right the first time. I think we can easily foresee that if we’re seeing success on a relapse trial, that’s going to lead to success at treating the disease in general.”
Firm foundation: “The thing to know about medulloblastoma therapy is we have a good foundational therapy on which to build,” says Giles Robinson, MD. “What we’re trying to do at St. Jude is take that standard therapy and make it better.”
No Escape for Cancer Cells
Researchers want to learn how well prexasertib is tolerated in children and the effects it may have on medulloblastoma. Jett and other patients receive prexasertib every two weeks, along with one of two standard chemotherapy drugs, gemcitabine or cyclophosphamide.
Adults with other types of malignant tumors have tolerated prexasertib well. These observations fueled the idea that children with cancer might also benefit.
The trial will last for two to three years, during which Robinson and his St. Jude collaborators can also determine if prexasertib has a helpful effect on attacking medulloblastoma tumors. If the medication works against tumors that have come back or not responded to standard treatments, it may also be tested as a front-line treatment in newly diagnosed patients.
“For many years, we’ve known chemotherapy is a good agent to use against medulloblastoma,” Robinson says. “But unfortunately, cancer cells have the ability to repair themselves and escape the damage chemotherapy has caused.
“Prexasertib interferes with the repair pathway the cancer cells are manipulating,” he adds. “By instigating damage with chemotherapy and then using prexasertib, we’re hoping to see the disease melt away in comparison to using chemotherapy alone.”
In the meantime, Jett’s participation in SJELIOT allows him to spend a lot of time at home with his parents and brothers between treatments, playing in what his mom calls his “wild man” ways and tooling around his family’s large property on his favorite ride-on truck.
When Jett first arrived at St. Jude in fall 2018, he resisted being poked and prodded. Today, he understands that his clinical team is there to help.
“He’s a good sport. He’s amazing,” Amy says. “Now, looking back, I see there was this fight in him that has gotten him through all this. He’s still Jett . . . he’s still crazy little Jett. We call him Jett Fighter.”
Robinson praises Amy; her husband, Chris; and others who travel this road with their children.
“I have the ultimate respect for the parents who go through this,” Robinson says. “They’re the superstars. They care about the things that are most important in life—and that’s their children.”
For Amy, the respect reflects right back to St. Jude.
“We’re thankful there’s a place like St. Jude for these kids. We’re grateful there are other options,” she says. “Yes, it’s a sacrifice for me to be here and be away from my family and my home and my other kids, but I feel like I’m giving Jett the best care he could possibly get.”
From Promise, Winter 2020