By Alicia Dirado and Shawn Le
A federal program is helping four City of Hope physicians translate their promising therapeutic ideas into clinical trials, speeding important treatments to patients for a variety of cancers.
The National Cancer Institute (NCI) Paula Calabresi Award for Clinical Oncology, or K12 for short, supports medical researchers who want to develop and pursue a clinical trial from its very beginnings.
At any one time, four City of Hope physicians hold a K12 grant, which provides as much as $75,000 each year for five years, as well as other funds to back research.
Karen Reckamp, M.D., assistant professor in the divisions of Medical Oncology & Therapeutics Research and Hematology & Hematopoietic Cell Transplantation, and Mike Chen, M.D., Ph.D., assistant professor in the Department of Neurosurgery, are the two latest physicians to be awarded the grants, sharing the distinction with existing grantholders Vincent Chung, M.D., and Jana Portnow, M.D., both medical oncologists.
Reckamp is no stranger to clinical trials. Before joining City of Hope, she co-directed UCLA’s Lung Cancer Specialized Program of Research Excellence clinical trials core.
The K12 backs her pursuit of better treatments for non-small cell lung cancer, which desperately needs answers; only about 16 percent of those diagnosed with it survive for five years.
Reckamp investigates the potential of cyclooxygenase-2 — known by the shorthand COX-2 — in lung cancer therapy.
The K12 grant helps Reckamp investigate how the COX-2 inhibitor celecoxib (popularly known as Celebrex) appears to boost the effectiveness of the targeted cancer drug erlotinib (known by the trade name Tarceva). Not only is Reckamp studying the pathways that help celecoxib do its work, though; she also is looking at markers in blood and tumor tissue that are related to outcomes.
“Our initial studies showed that patients with lower levels of certain proteins in their blood had better tumor responses to treatment than those with high levels,” Reckamp said.
If the biomarker candidates prove successful, physicians could eventually use the markers to test patients before they even start therapy, to ensure that patients would likely benefit from the treatment.
Already, Reckamp is planning to lead a multicenter, randomized phase II clinical trial to test the effectiveness of erlotinib and celecoxib compared to erlotinib and placebo in patients with non-small cell lung cancer; she also will compare patients’ tissue samples before and after treatment to see how the therapies affect the tumors’ inner workings.
Brain tumors have a deadly reputation, and for good reason. But Chen, of the Brain Tumor Program, aims to change that.
“We’re investigating how interference of STAT3, a gene that is critical for tumor growth, can be used to kill cancer cells in the brain,” said Chen. “Traditional treatment with surgery, while often beneficial, is rarely curative. The toxicity of chemotherapy or radiation further limits effective treatment.
“My goal is to use City of Hope’s tremendous expertise with the basic biology of STAT3 to develop a potent new weapon against these aggressive cancer cells.”
Chen will work with Richard Jove, Ph.D., chair of the Division of Molecular Medicine and co-leader of the Developmental Cancer Therapeutics Program, who has pioneered research into STAT3.
The K12 grant will help him evaluate the use of short-interfering RNA and sorafenib (called Nexavar), an approved cancer drug that may inhibit STAT3, in patients with metastatic brain tumors. He aims to start clinical trials in three to five years.
“Our unique approach is the delivery of a STAT3 inhibiting agent using convection-enhanced delivery, a highly specialized form of direct injection into the tumor,” said Chen. The method can direct high doses of medication where they are most needed.
City of Hope physicians have participated in the K12 program since 1991, sharing the distinction with centers such as M.D. Anderson Cancer Center and the Mayo Clinic. The institution’s K12 program helps develop the careers of physicians who have completed a fellowship in oncology. The funds help participants administer all phases of a clinical trial and work as a team with basic scientists to transfer discoveries into patient-centered research.