The German Childhood Cancer Foundation (Deutsche Kinderkrebsstiftung, DKS) is providing EUR 2.2m to fund the first phase III clinical trial to investigate the best treatment options for certain types of childhood brain cancer with a chronic course. Initiated by the Hopp Children’s Cancer Center Heidelberg (KiTZ), the trial will compare two standard chemotherapy treatments and a targeted therapy to establish which is the most effective and well tolerated as a standard therapy for young patients worldwide.
Low grade gliomas (LGGs), a group of slow-growing brain tumors, are the most common brain tumors affecting children. They occur mainly in young children and often have a chronic course. The survival rate ten years after diagnosis is 90 percent. The tumors are characterized by alternating phases of growth and stasis. Many children will therefore need several, sometimes up to five, different therapies.
In a third of young patients, the tumors cannot be surgically removed and lead to impaired vision, paralysis on one side of the body, hormone disorders and seizures. “At the moment, we can’t cure these tumors. All we can do is use chemotherapy to stop their growth or suppress them for as long as possible,” says KiTZ Director Olaf Witt, who is head of the DKFZ’s clinical cooperation unit for pediatric oncology and also works at University Hospital Heidelberg (UKHD) as a managing chief physician. “But the treatment sometimes has serious side effects and long-term consequences for patients,” he adds.
A potentially gentler form of therapy involves MEK inhibitors. Research projects led by KiTZ Director Stefan Pfister and group leader David Jones have detected overactivation of a molecular signaling pathway in the LGGs which allows the cells to proliferate uncontrollably and the tumors to grow. The MEK inhibitors target this dysregulation and have produced promising results in phase I/II clinical trials with LGG patients.
“Until now, however, there has not been any systematic comparison to investigate whether this therapy is actually more effective than chemotherapy for young people and whether it has fewer side effects in the long term,” explains Witt. The global LOGGIC trial (Low Grade Glioma in Children), which is being run at the KiTZ in cooperation with its two supporting institutions, UKHD and DKFZ, has been made possible by the German Childhood Cancer Foundation (DKS), which is providing funding of EUR 2.2 million. It will be the first phase III clinical trial in this field that aims to identify which treatment helps patients the most.
Around 300 patients will be allocated at random to one of three treatment arms: a combination therapy with the chemotherapy drugs usually used to treat LGGs (carboplatin and vincristine), a treatment with the standard chemotherapy drug vinblastine, and a therapy with trametinib, a MEK inhibitor.
“We are not only investigating the effectiveness and tolerance of the therapy, but also seeing whether, overall, it leads to improved vision and everyday motor functions for patients,” says Olaf Witt. “If patients in either of the two chemotherapy arms find their treatment is ineffective, they will be able to continue treatment with trametinib. In addition, we will, for the first time, be carrying out comprehensive molecular tests on genetic changes in all the tumors to find out why some LGGs respond well to treatment and others don’t.”
The trial will take place throughout Europe and in Australia, in 15 countries overall, and the first patients are to be recruited at the start of 2021. Olaf Witt is confident that the trial will bring about lasting improvements in the treatment of young patients: “Thanks to the large case numbers and the randomized design, we are expecting very robust evidence that can be used to introduce a better, gentler new standard therapy for young LGG patients worldwide.”