Every year, some 17,000 Americans die from glioblastoma multiforme, a terminal, aggressive brain tumor with an average survival rate of six to 12 months. It is the most common form of malignant brain tumor, and it led to the death last year of longtime Senator Edward Kennedy.
A vaccine that has shown initially positive results in helping control glioblastoma multiforme is now under further investigation at UCSF’s Brain Tumor Research Center.
Andrew T. Parsa, MD, PhD, a UCSF neurosurgeon, recently began a phase II clinical trial of a personalized vaccine with the trademarked name of Oncophage. The trial, known as the Upfront study (officially called “Phase II, Single-Arm, Open-Label Investigation of HSPPC-96 Vaccine with Concurrent Temozolomide for Patients with Newly Diagnosed Glioblastoma Multiforme”), tests Oncophage’s effectiveness when coupled with early detection and removal of the tumor as well as rounds of radiation and chemotherapy.
“Essentially, we’re covering all bases at once,” Parsa said. “A patient receives surgery, chemotherapy and the vaccine. The thought is that we’re going to try to extend survival, to put this thing into remission and make it as much of a chronic disease as possible.”
Made from a patient’s own tumor, the vaccine is designed to elicit an immune response from the body that attacks the tumor while leaving other cells unharmed. The Upfront trial focuses on patients who have developed glioblastoma for the first time, while another of Parsa’s ongoing clinical trials tracks the vaccine’s success in 30 patients with recurring glioblastoma.
A Massachusetts company called Antigenics produces the vaccine by isolating and extracting gp96, a heat shock protein whose job it is to chaperon, or transport, other proteins inside each cell from one location to another. Immunizing patients with their own heat shock protein taken from the tumor cells has produced an increase in T-cell activity. Parsa likened the vaccine to a flu shot: While a flu shot will not cure an ill person, it could prime the immune system to fight the flu and prevent its return after initial exposure.
“The Upfront study will answer the very important question as to whether or not giving the vaccine initially at the time of the first diagnosis of the tumor is better than giving it at the time of recurrence,” said Mitchel S. Berger, MD, director of UCSF’s Brain Tumor Research Center. “This should give us tremendous insight into the usefulness of the vaccine as an adjuvant therapy in the newly diagnosed setting.”
Berger oversees UCSF’s brain tumor Specialized Programs of Research Excellence (SPORE) grant, which is administered by the National Cancer Institute in an effort to put the most promising cancer treatment research on a fast track. Parsa’s trial received $150,000 through SPORE, and another $150,000 from three patient advocacy groups – the American Brain Tumor Association (ABTA), the National Brain Tumor Society and Accelerate Brain Cancer Cure.
The executive director of ABTA, Elizabeth Wilson, described Parsa’s clinical trial as “the future of brain tumor treatment.”
And no prospective outlook could please Chancellor Susan Desmond-Hellmann, MD, MPH, more.
Desmond-Hellmann was a practicing oncologist for two years. “The worst conversation I’d have with a patient is, ‘We’ve run out of ideas; I don’t have anything else to try but to call hospice and manage pain,’” she said. “I hated that. I hated being confronted with defeat.”
Then, when Desmond-Hellmann started doing research and development in oncology, her thinking shifted. Instead of “We don’t have anything for you,” the goal became “We have something for that.”
“And for me,” she said, “that’s the best thing about being at a place as innovative as UCSF.”
Eight patients have been enrolled in the trial, and three are receiving the vaccine treatment along with traditional therapies. Each patient has at least four injections, which are administered under the skin like a flu shot.
Joyce Wheatley, 58, of Winton, California, enrolled in the trial last summer. Since her surgery on Aug. 5, 2009, soon after her diagnosis, she has received the vaccine and radiation therapy, and she is about to begin 18 months of chemotherapy.
“I feel better than I’ve felt in years,” Wheatley said. “I really hope to hear in the future that it has helped someone else.”
She is the first Upfront study patient to receive the full host of treatments, and described participating in the trial as a unique experience. “I thought that was pretty cool when Dr. Parsa said, ‘You just made history.’”
Through the Upfront study, Parsa and his colleagues hope to further establish that a patient’s immune system can be primed to fight the return of glioblastoma multiforme. Based on blood tests before and after vaccinating patients, Parsa said they are seeing results. “I know that we have a tumor-specific immune response,” he said.
The other significant question the researchers hope to answer is, “Who will most likely benefit from an immunotherapy approach?” Some patients’ cancer appears to be resistant to the immune system, which raises the question of whether a technique for reversing that immunoresistance can be developed.
“If you answer those two questions,” Parsa said, “then you’re way down the road to implementing this therapy broadly. And we have the infrastructure and the setup, and we’ve designed the protocol, to get that information very easily.”
Photos by Susan Merrell