The stories are heartbreaking: An adolescent suffering from a noncancerous tumor that distorted her face; a young boy with a tumor on his neck that threatened his ability to breathe; and another youngster experiencing uncontrollable pain with a massive tumor on his neck, chest and arm.
All three of these children, along with an estimated 2.5 million others worldwide, suffer from a genetic disorder that causes inoperable tumors called plexiform neurofibromas to grow on nerves throughout their bodies. Known as neurofibromatosis type 1, or NF1, this disorder can cause pain, disfigurement, blindness and motor dysfunction, and the tumors sometimes become cancerous.
These children now have a chance for a better life because of Dr. Brigitte Widemann, a pediatric oncologist at the National Cancer Institute who developed the first successful therapy to treat this debilitating disease after nearly two decades of study.
“Dr. Widemann pioneered the research leading to a world-class clinical trial program for neurofibromatosis type 1 and the development of the first Food and Drug Administration- approved medical therapy,” said Dr. Tom Misteli the director of the National Cancer Institute’s Center for Cancer Research. “This treatment option gives patients and their families a glimmer of hope. It really lifts them up.”
After years of searching for treatments to help children with NF1 tumors, Widemann had reason to believe that a drug that had failed its clinical trial as a treatment for breast cancer might work on these tumors.
This was a challenge for which Widemann was particularly suited. She had experience conducting clinical trials for children with cancer and NF1. However, unlike cancer, very little was known about the natural history of the growth of these tumors for a long time—critical knowledge that is required for drug approvals.
To address this problem, Widemann put together a study of 259 participants to chart the growth of their tumors, creating a baseline for the progression of the disease. Widemann and her team regularly examined these children with benign tumors for 10 years and detailed how each child’s tumors changed.
“Dr. Widemann created an entire field of clinical data about these tumors in addition to her day job of leading the pediatric oncology department,” said Jaishri Blakeley, a professor at Johns Hopkins University.
To set up the clinical trial to test selumetinib, the drug that Widemann believed might work on the tumors, she and her team worked closely with the NCI Cancer Therapy Evaluation Program and the pharmaceutical company AstraZeneca to evaluate if the drug would benefit patients with NF1 tumors and was worth taking to the FDA for approval.
She and her colleagues ran a phase 1 clinical trial with 24 children ages 3 to18 to test the safety of the drug, and a phase 2 clinical trial with 50 children ages 3 to 17 to test its effectiveness. After a year of participating in the phase 2 clinical trial with the drug, the children gained strength and agility. Tumors shrank in 70% of the children, and some who had been on pain medications were able to come off them.
The mother of a young boy who participated in Widemann’s studies and clinical trials hailed the breakthrough on Twitter: “Over 10 years of clinical trials, four rounds of experimental medicine, hundreds of blood draws, tens of thousands of miles traveled, weeks away from the family, helped to create this opportunity to make life better for children facing NF (tumors),” tweeted Kelly Carpenter.
As Widemann sees it, the new treatment is not yet a cure—many children still have disabling tumors—but “it is making children feel better and have a better quality of life.”
“The finding of tumor shrinkage is a big step forward and inspires us to work even harder toward additional progress in NF1 therapies,” Widemann said.
In addition to her success with NF1 benign tumors, Widemann and her team followed atypical tumors to see why and how they turned cancerous. They found that early surgical removal of these pre-cancerous tumors may prevent them from becoming malignant.
“She is a cutting-edge clinical researcher and a wonderful mentor,” Dr. Norman Sharpless, director of the National Cancer Institute, said of Widemann. “She is eager to continue to solve these complex medical issues. She’s a great steward for science.”