NIH grant furthers promising metastatic melanoma clinical trials for Providence Cancer Center patients

March 15, 2013

PORTLAND, Ore. — Patients with advanced melanoma are getting a boost from work being done at Providence, thanks to a grant from the National Institutes of Health.

Providence Cancer Center researchers Brendan Curti, M.D., and Marka Crittenden, M.D., Ph.D., have been notified they received the NIH grant for $144,855 to aid in the study of a novel combination treatment of metastatic melanoma.

The two researchers and Steven Seung, M.D., Ph.D., all part of the Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute at Providence Cancer Center, developed a clinical research trial using stereotactic body radiotherapy, or SBRT, with high-dose interleukin 2 immunotherapy, or IL-2.

Results of a 12-patient pilot study were published last year in the journal “Science Translational Medicine” in a paper titled “Phase 1 Study of Stereotactic Body Radiotherapy and Interleukin-2: Tumor and Immunological Responses.” It found the combination treatment resulted in a response rate of 60 to 70 percent in patients with advanced melanoma and renal cancer, which are fatal illnesses in the majority of people.

A second clinical trial is now underway, with the goal of enrolling 44 patients.

“We were immensely pleased with the results with the first trial, but are still working to understand why this treatment worked so well,” said Dr. Curti, director of the biotherapy research program at Providence Cancer Center.

“This new NIH grant will allow us to focus on the ‘why’,” said Dr. Crittenden, director of translational radiation research, Providence Cancer Center, and a radiation oncologist with The Oregon Clinic. “Gaining that knowledge may allow us to incorporate this same treatment in the care of patients with other aggressive tumors.”

“Receiving an NIH grant is always an honor, but never more so than in this very difficult time of increased competition for fewer research dollars,” said Walter J. Urba, M.D., Ph.D., director, Robert W. Franz Cancer Research Center in the Earle A. Chiles Research Institute, Providence Cancer Center. “We are very proud of our investigators and this acknowledgement of the significance of their research.”

When they began working on this project, Dr. Curti, Dr. Crittenden and Dr. Seung knew that the combination of radiation and immunotherapy had been tried about 20 years ago, but with a very different radiation technique. The early work was not effective. So they built on the idea.

They believe the memory immune cells are significantly boosted by the combination of SBRT radiation and IL-2, but other mechanisms may also come into play.

It is already known that the immune system has the ability to attack cancer cells. The main way is with an immune cell called a T-cell. T-cells can recognize what is foreign in the body and eliminate it. They do this by looking for proteins that don’t belong in the body. However, cancers can hide from T-cells in many ways, including concealing the proteins that the T-cells would use to recognize the cancer as foreign to the body.

Providence researchers pursued the idea of using a high dose of focused radiation on a tumor to break open some of the cancer cells in the tumor, helping to release proteins the T-cells could recognize. For the T-cells to really thrive, the ones that recognized the cancer proteins need another signal to divide and conquer. One of the strongest signals to make the T-cells divide is interleukin-2. As these T-cells rev up and attack the melanoma, they also become memory cells – powerful tools in future cancer battles.

Providence installed the high-dose stereotactic body radiotherapy machine that allowed for this novel approach at the time the new cancer center opened in 2008. In addition, Providence treats a high volume of patients with melanoma, and many of them undergo IL-2 therapy. It seemed natural to combine the two.

Melanoma is diagnosed in 80,000 Americans every year. It is potentially curable if caught in the early stages. When it spreads to other organs, the survival rate is 5 percent or less.