Open to all eligible children with relapsed leukemia and solid tumours, the study will closely monitor and analyze the side effects of Carfilzomib to determine the maximum dose children can safely tolerate. The trial will cost approximately $3.5 million (U.S.) to administer.
Dr. Aru Narendran of the Alberta Children’s Hospital and University of Calgary and Dr. Jessica Boklan of Phoenix Children’s Hospital are the principal investigators in a new phase I clinical trial, studying the side effects of a drug called Carfizomib on children with high-risk cancers. Dr. Tony Truong, co-principal investigator at the Alberta Children’s Hospital, along with U of C clinical research staff, Karen Mazil and Pina Giuliano, are helping to monitor side effects and analyze findings from the study.
Previously tested and approved for use in adult patients, Carfilzomib has shown promise for treating adults with multiple myeloma—a high-risk leukemia. Studies in a University of Calgary lab revealed that the drug also acts on pediatric cancer cells. These findings from Dr. Aru Narendran’s lab were presented last year at a meeting of the American Association of Cancer Research.
Carfilzomib was originally synthesized from a natural substance made by a soil bacterium to protect itself. Scientists in Dr. Craig Crews’ lab at Yale University serendipitously discovered in 1998 that Carfilzomib also has strong anti-cancer properties. Their discovery led to clinical drug trials and FDA approval in 2012 for use in adults with multiple myeloma—a high-risk leukemia.
Carfilzomib’s anti-cancer properties lies in its ability to inhibit a mechanism called the proteasome, which cancer cells use for survival. Because cancer cells divide and multiply so quickly and recklessly, they make a lot of mistakes, leading to abnormally formed proteins within the cancer cells. These poorly formed molecules put stress on the cancer and threaten its survival. To get around this, the cancer cells increase their use of a mechanism called the proteasome to repair their mistakes. But by inhibiting proteasomes, Carfilzomib prevents the cancer cell from repairing itself and ultimately helps it to die of its own imperfections.
“The beauty of this drug is it goes after a mechanism used by all cancer cells, so it can be used against different cancers,” says Dr. Narendran a pediatric cancer researcher with the Experimental and Applied Therapeutics (ExpAT) program at the Alberta Children’s Hospital and the University of Calgary. “Normal cells don’t make so many mistakes, so this drug will be less toxic to normal cells, which may mean fewer side effects for children.”
Another promising attribute of Carfilzomib is that it works synergistically with other chemotherapies to boost their ability to kill cancer cells. This is especially important for chemo-resistant cancers.
“It’s kind of a safety net,” says Dr. Narendran. “Because the chemo agents and their toxicity are already known to us, we can use these chemotherapies with Carfilzomib to boost their potency for better outcomes.”
Although Carfilzomib looks promising, Dr. Narendran stresses that “What we know so far comes only from adult patients or from laboratory studies against pediatric cancer cells. We do not know if it will actually offer any benefit to pediatric cancer patients yet.”
As a phase I clinical trial, the study is not intended to cure children, but to understand its toxicities and determine suitable doses for treating children in the future.
Still, it is the first important step in a long quest to find safe and effective treatments for children with incurable cancers.
If it lives up to its potential, Carfilzomib may one day offer hope for children with incurable cancers.
If you are interested in this study for your child, please speak with your child’s oncologist to determine eligibility.