First Arizona-Based Clinical Trial for Children with Cancer Established
Oncology researchers at the University of Arizona Children's Research Center and Phoenix Children's Hospital are collaborating to try to find better, less toxic ways to treat children with cancer. They have developed a partnership called ACTION (Arizona Children's Therapeutic & Investigational Oncology Network) to give children in Arizona greater access to cutting-edge clinical trials for cancer treatment.
The clinical trials are aimed at helping those with high-risk leukemias or solid tumors that have not responded to conventional therapies, said Rochelle Bagatell, MD, UA assistant professor of Pediatrics in Hematology/Oncology. "These most serious cancers are also those that call for the most aggressive treatment. So, while the treatments can be life-saving, there are significant and long-lasting side effects," Dr. Bagatell said.
"Our hope is that our research may lead to treatments that are just as effective without as many side effects," said Jessica Boklan, MD, director of oncology research at Phoenix Children's Hospital. She explained that children typically can tolerate very intensive treatment regimens, so high-risk pediatric oncology patients have benefited greatly from the 'more is better' approach to treatment in the past. However, she said, "advances in medicine may now allow development of more specifically targeted treatments for childhood cancers."
Typically, when new cancer drugs are developed, they first go through a "Phase I" trial, which has the goal of establishing the dose of a drug based on how severe the side effects are in patients. With this particular Phase I trial, however, the doctors are attempting to determine whether doses for newer, more targeted drugs can be established based on biological effects rather than on toxicity alone.
The difference is that, rather than simply identifying the unwanted effects a drug may have, such as damage to major organs, the researchers also document changes in the cell biology, often at a molecular level, to note differences in the drug's interaction with cancer cells vs. normal cells. The hope is that this will reveal which therapies go right to the source of the cancer most effectively.
Drs. Bagatell and Boklan are pursuing this new approach in concert with other major pediatric centers, including Memorial Sloan Kettering Cancer Center, Johns Hopkins University, and MD Anderson. The researchers also are making use of novel techniques to isolate tumor cells from blood and bone marrow, which would eliminate the need for invasive biopsies to study effects of drugs on tumor cells. To date, seven children from Phoenix and one child from Tucson have been enrolled in a study of these new techniques. Researchers in partner institutions around the country are sending blood samples to the UA Children's Research Center for evaluation. At the study's completion, researchers hope to know if this new approach to isolating tumor cells works and if this approach can be used to determine whether newer, more targeted anti-cancer drugs are altering important molecules in tumors.
The drug being studied, 17-allylaminogeldanamycin (17AAG), has been a focus of the work done by researchers at the UA Children's Research Center over the past decade. This drug binds to heat shock protein (hsp90), a cellular protein that plays an important role in cell growth, differentiation and cell death.
"The scientific and clinical strengths in pediatric oncology in this state are coming together, and we now have the opportunity to study a very promising new drug in a clinical trial for the children who need it most," says Dr. Bagatell. "Children with cancer need newer, more effective drugs. In the past our patients had to travel all over the country to participate in clinical trials. We hope that our efforts will bring us closer to the goal of finding better and less toxic treatments for these children. By working together we can do this right here in Arizona."