Immunotherapy and SBRT Study in Borderline Resectable Pancreatic Cancer
Status:
Terminated
Trial end date:
2016-07-30
Target enrollment:
Participant gender:
Summary
Unfortunately, despite the best clinical efforts and breakthroughs in biotechnology, most
patients diagnosed with pancreatic cancer continue to die from the rapid progression of their
disease. One primary reason for this is that the disease is typically without symptoms until
significant local and/or distant spread has occurred and is often beyond the chance for cure
at the time of the diagnosis. The lack of any treatment to substantially increase long term
survival rates is reflected by the poor outcomes associated with this disease, specifically
time to disease progression and overall survival.
However, another important part of the body is now being looked at as a target for therapy
against this disease - the immune system. Scientists have clearly shown that pancreatic tumor
cells produce a number of defective proteins, or express normal proteins in highly
uncharacteristic ways, as part of this cancer. In some cancers, these abnormalities can cause
an immune response to the cancer cells much in the way one responds to infected tissue. In
progressive cancers however, the immune system fails to effectively identify or respond to
these abnormalities and the cancer cells are not attacked or destroyed for reasons not yet
fully understood. This clinical trial proposes a new way to stimulate the immune system to
recognize pancreatic cancer cells and to stimulate an immune response that destroys or blocks
the growth of the cancer.
This new method of treatment helps the immune system of pancreatic cancer patients to
"identify" the cancerous tissue so that it can be eliminated from the body. As an example,
patients with certain diseases may require an organ transplant to replace a damaged kidney or
heart. After receiving their transplant, these patients receive special drugs because they
are at great danger of having an immune response that destroys or "rejects" the transplanted
organ. This "rejection" occurs when their immune system responds to differences between the
cells of the transplanted organ and their own immune system by attacking the foreign tissue
in the same way as it would attack infected tissue. When the differences between foreign
tissues and the patient's body are even larger, as with the differences between organs from
different species, the rejection is very rapid, highly destructive, and the immunity it
generates is longlasting. This is called hyperacute rejection and the medicine used to
immunize patients in this protocol tries to harness this response to teach a patient's immune
system to fight their pancreatic cancer just as the body would learn to reject a transplanted
organ from an animal.
To do this, Algenpantucel-L immunotherapy contains human pancreatic cancer cells that contain
a mouse gene that marks the cancer cells as foreign to patient's immune systems. The immune
system therefore attacks these cancer cells just as they would attack any truly foreign
tissue, destroying as much as it can. Additionally, the immune system is stimulated to
identify differences (aside from the mouse gene) between these cancer cells and normal human
tissue as foreign. This "education" of the immune system helps treat the patient because
pancreatic cancer cells already present in a treated patient are believed to show some of the
same differences from normal tissue as the modified pancreatic cancer cells in the product.
Due to these similarities, the immune system, once "educated" by the Algenpantucel-L
immunotherapy, identifies the patient's cancer as foreign and attacks.
Historically, external beam radiation has been part of the treatment of pancreatic cancer,
both before and after surgical resection. Recent breakthroughs in technology now allow for
more intensive doses of radiation to be delivered to the body with greater precision. These
newer, more precise radiation treatments, called stereotactic body radiation, deliver more
intensive radiation to a locally advanced tumor and are now being employed in the treatment
of pancreatic cancer. Stereotactic body radiation may increase the chances that surgery will
successfully remove a pancreatic cancer.
In this experimental study, all patients will be given a strong combination of antitumor
chemotherapy while receiving injections of an immunotherapy drug consisting of two types of
pancreatic cancer cells that have been modified to make them more easily recognized and
attacked by the immune system. The investigators propose to test this new treatment paradigm
along with stereotactic body radiation in patients with borderline resectable pancreatic
cancer to demonstrate that treatment with this combination of therapies increases the time
until the tumor progresses as well as overall survival.