Clinical trial may give patients with recurring tumors more options

by Jessica Howard Ennis
photo by Dana Johnson

Sarah Shingleton and her mother, Brenda.

"Should I wear the blonde wig, the red wig or no wig?" 15-year-old Sarah Shingleton, jokingly asked when discussing getting her picture taken. Choices are very important to Sarah, even small ones about her hair.

Sarah has made another choice, one which may save her life. She and her mother, Brenda, traveled from West Virginia so Sarah could participate in a phase I clinical trial at the Childhood Cancer Program at the Monroe Carell Jr. Children's Hospital at Vanderbilt.

Sarah has been living with glioblastoma multiforme - a highly malignant and fast growing type of brain cancer - for four long years. The average survival time for patients with this type of cancer is usually only 12 to 18 months, because of tumor re-growth.
At first, Sarah's friends didn't believe her when she said she was sick because she was able to go to school, play volleyball and do all the things healthy girls her age were doing. But what they couldn't see were the tumors growing in Sarah's brain.

Migraine headaches and vomiting was the first sign something was wrong, and Bell's palsy (temporary paralysis on one side of her face) prompted a trip to the Emergency Department.

Brenda still didn't even know it was serious and admits she had Sarah working on her homework between tests at the hospital. Finally, test results showed Sarah had tumors in her brain, and the prognosis was grim.

"You can't see brain tumors and it has a hold on you before you can get a hold on it," Brenda said.

Sarah has already endured half a dozen surgeries back home in West Virginia - twice were attempts to remove tumors, but each time they returned. Since January, Sarah has been at Children's Hospital participating in an important new clinical trial to see if a new drug can stop her brain tumors from growing, and perhaps even shrink them in size.

"When you have a sick child you have to figure out what you think is best," Brenda said. "I read some information about a similar trial in adults and it offered some hope."

The trial is called "Phase I Study of Erbitux (Cetuximab) In Pediatric Patients With Refractory Solid Tumors." It is the first study of Erbitux in childhood malignancies.

The trial, lead at Children's Hospital by John Kuttesch, M.D., associate professor of Pediatric Hematology/Oncology, is one of several clinical trials offered by the Pediatric Oncology Experimental Therapeutics Investigation Consortium (POETIC). The trial combines Erbitux, an inhibitor of cell growth with Irinotecan, which is already being used to fight childhood solid tumors, to determine the effects of this combination of drugs in children with recurrent tumors. The study will also determine what dosage of the medication is most effective in children.

"We don't have effective therapies for patients with glioblastoma and other recurrent solid tumors, and our goal with the POETIC trials is to identify novel drugs to offer potential active drug therapies to this group," Kuttesch said.

Several Pediatric Oncology Centers associated with top comprehensive cancer centers in the country are also participating in this clinical trial for children 2 to 18 years old with recurring solid tumors. A solid tumor is an abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors may be benign (not cancerous), or malignant (cancerous).

"Our POETIC group is evaluating novel drugs that have good potential for activity against pediatric tumors, and designs these trials to determine the effects of these drugs on the patient and the cancer as well as learn more about the biology of these cancers," Kuttesch said. "The overall survival rate for childhood cancer is 70-80 percent, but that means up to 30 percent of childhood cancer patients don't survive. Our goal is to improve the survival of these children by the use of novel drugs such as Erbitux."

Currently, four children have been enrolled at Children's Hospital. So far the treatment is working for Sarah, whose tumor has shown no signs of growth.

Sarah, who is very realistic about the seriousness of her condition, said Kuttesch told her she was in control, and could stop treatment whenever she wanted to. Sarah says she plans to see the study through as long as needed. If her tumors or any other participants' tumors, begin to grow, they will no longer be enrolled in the trial.

"The interesting and promising news is that patients with malignant brain tumors are able to stay in the trial longer," Kuttesch said. "Potentially, this drug combination may be active in children with brain tumors."

Added Brenda, "Hopefully with continued use, doctors can try and figure out a maintenance treatment that the body can take so people can have a good quality of life."

Sarah and her mom are staying with family in town, and travel home during breaks between treatments to see Sarah's dad and sister. Sarah comes to the Children's Hospital Cancer Clinic every day for 11 days to receive treatment, and then she receives either a week or two off. She is currently on her third round of treatment, and says she doesn't know how long she will continue the trial.

The trial is continuing at Children's Hospital potentially through spring of 2007. Then researchers will evaluate the results and will determine if they can proceed with a more focused trial.

"This trial gives us hope, and that is the most important thing to us right now," Brenda said.