Research from Rutgers Cancer Institute of New Jersey shows that the 'first in man' series of vaccine injections given directly into a pancreatic cancer tumor is not only well tolerated, but also suggests an "encouraging" period of stable disease. Results from a Phase I clinical trial conducted at the Cancer Institute of New Jersey are being given as part of a poster presentation at the American Association for Cancer Research (AACR) Pancreatic Cancer: Innovations in Research and Treatment conference being held in New Orleans this week.
Vaccine therapies are designed to strengthen the body's immune defenses and are typically given in the arm or leg. In a previous study, investigators at the Cancer Institute showed that using a vaccine treatment for bladder and breast cancer tumors in laboratory models resulted in a reversal of the traditional immune blockade, as well as the development of tumor specific immunity throughout the body. This tumor specific immunity showed the potential of blocking the growth of the original tumor as well as eliminating small tumor deposits that can cause the cancer to spread. Building on this research, investigators further tested this vaccine in a direct injection method in patients who were not candidates for surgery to remove their cancer. The Cancer Institute's Associate Director for Education and Training Edmund Lattime, PhD, who is also a professor of surgery at Rutgers Robert Wood Johnson Medical School, and Elizabeth Poplin, MD, co-director of the Cancer Institute's Gastrointestinal/Hepatobiliary Program and a professor of medicine at Robert Wood Johnson Medical School are the lead investigators of the study.
The focus of the research is the investigational vaccine known as PANVAC. PANVAC contains gene additives that might stimulate a person's immune system to recognize and develop an immune response to the disease. Two types of PANVAC were utilized in this trial. PANVAC-V, which uses the same virus as the smallpox vaccine, is a live but weakened vaccinia vaccine (meaning the virus can still multiply) that is given in the arm. PANVAC-F (a live Fowlpox virus that cannot multiply) is injected into the tumor itself and subsequently into the arm as a booster. Direct tumor injection takes place through an endoscopic ultrasound, in which a scope is inserted through the mouth and into the stomach so that the tumor in the pancreas can be seen.
During the first phase of the study, patients were evaluated for toxicity, tumor progression and the presence of tumor markers for pancreatic cancer. Two patients were removed from the first part of the study after two weeks due to rapid disease progression; one died six months after first being placed on the trial and the other after one month. The second part of the trial involved giving a higher dosage of PANVAC-F during direct injection of the tumor. During this phase, one patient was removed due to rapid disease progression and died one month after, while a second patient withdrew and died after 16 months.
Of the remaining 10 patients from both dose levels, three were shown to have distant metastatic disease with a survival range of six to 22 months. The other seven patients presented without distant metastasis with a survival range of four to 36 months. Of this latter group, none developed disease that spread beyond the original tumor into other organs but instead died of a secondary condition associated with locally progressive pancreas cancer. All but one of the ten patients transitioned to treatment with gemcitabine, which is a standard therapy for pancreas cancer. A series of genetic analyses for day one and day 14 patient immune responses is currently being examined.
"While the median survival rate for patients without distant metastasis was nearly a year-and-a-half with this treatment, there was one patient whose disease remained clinically stable for nearly three years. When you have a disease that only carries a five-year, six percent survival rate, these findings are very encouraging and will hopefully lead to more effective ways of managing and treating this disease," note the researchers.
Along with Drs. Lattime and Poplin, authors include David August, Cancer Institute and Robert Wood Johnson Medical School; Tamir Ben-Menachem and Hazar Michael, both Summit Medical Group; Aparna Repaka and Renee Artymyshyn, both Robert Wood Johnson Medical School; Chang Chan, Cancer Institute; James L. Gulley, National Cancer Institute (NCI); and Robert S. DiPaola, Cancer Institute.
The work was supported by the NCI Cancer Therapeutics Evaluation Program and by NCI U01-CA07031 and P30-CA72720.