Immunotherapy Study for Surgically Resected Pancreatic Cancer

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. The 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 significantly increase long term
survival rates is reflected by the poor outcomes associated with this disease, specifically
time to disease progression and overall survival.

These disappointing facts typically shape discussions of treatment options for patients with
this disease. 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 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 the abnormal components found in 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,
most people are aware that 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, perhaps like
differences between organs from pigs and the immune system cells of humans, the rejection is
very rapid, highly destructive and the immunity it generates is long lasting. 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, the investigators have placed a mouse gene into human pancreatic cancer cells so
that the immune system will easily recognize them as foreign, stimulating the patient immune
system to attack the vaccine cells just as they would any other animal cells. As part of the
process of destroying the immunotherapy cells, the patient immune system is stimulated to
identify as many differences from normal human as possible. This extra stimulation is thought
to encourage immune responses against the pancreatic cancer in the patient based on shared
abnormalities of pancreatic cancer vaccine cells and the patient's pancreatic cancer cells.

In this experimental therapy, patients are given injections of an immunotherapy consisting of
two types of cancer cells that the investigators have modified to make them more easily
recognized and attacked by the immune system. The investigators propose to test this new
treatment in patients with pancreatic cancer who have undergone tumor removal surgery but
remain at extremely high risk of disease progression to demonstrate that treatment with the
immunotherapy increases the time until the tumor recurs or increases overall survival when
given in combination with the current standard of care therapy for this disease.

For more information, please see our study specific website:
www.pancreaticcancer-clinicaltrials.com

Inclusion Criteria:

- A histological diagnosis of adenocarcinoma of the pancreas confirmed by pathology.

- American Joint Committee on Cancer (AJCC) Stage I or II Pancreatic carcinoma. Patients
must have undergone surgical resection for the tumor and extent of resection must be
either R0 (complete resection with grossly and microscopically negative margins of
resection) or R1 (grossly negative but positive microscopically margins of resection).

- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

- Serum albumin ≥2.0 gm/dL.

- Expected survival ≥6 months.

- Subjects must be able to take in adequate daily calorie intake based on judgment of
clinical investigator.

- Adequate organ function including:

- A. Marrow: white blood cells (WBC) ≥3000/mm3 and platelets ≥100,000/mm3.

- B. Hepatic: serum total bilirubin ≤2 x ULN mg/dL, ALT (SGPT) and AST (SGOT) ≤3 x upper
limit of normal (ULN).

- C. Renal: serum creatinine (sCr) ≤2.0 x ULN, or creatinine clearance (Ccr) ≥30 mL/min.

- First vaccination must be within 10 weeks after surgery.

- Patients must have the ability to understand the study, its inherent risks, side
effects and potential benefits and be able to give written informed consent to
participate. Patients may not be consented by a durable power of attorney (DPA).

- All subjects of child producing potential must agree to use contraception or avoidance
of pregnancy measures while enrolled on study and receiving the experimental product,
and for one month after the last immunization.

Exclusion Criteria:

- Age <18-years-old.

- Active metastases. Suspicious lesions on CT scans must be reviewed by a second,
different reviewer. If active disease not ruled out by second, different reviewer (at
clinical institution), a positron emission tomography (PET) CT or further imaging
tests or histology may be needed to rule out disease before enrollment is allowed.

- Other malignancy within five years, unless the probability of recurrence of the prior
malignancy is <5% as determined by the Principal Investigator based on available
information. Patient's curatively treated for squamous and basal cell carcinoma of the
skin or patients with a history of malignant tumor in the past that have been disease
free for at least five years are also eligible for this study.

- History of organ transplant.

- Current, active immunosuppressive therapy such as cyclosporine, tacrolimus, etc.

- Subjects taking chronic systemic corticosteroid therapy for any reason are not
eligible. Subjects may receive steroids as prophylactic anti-emetics, not to exceed 10
mg Decadron weekly. Subjects may also receive pulse doses for Gemcitabine
hypersensitivity, not to exceed Decadron 8 mg twice a day (BID) x 3 days prior to
start day of Gemcitabine. Subjects receiving inhaled or topical corticosteroids are
eligible. Subjects who require chronic systemic corticosteroids after beginning
vaccination, will be removed from study.

- Significant or uncontrolled congestive heart failure (CHF),myocardial infarction or
significant ventricular arrhythmias within the last six months.

- Active infection or antibiotics within 48 hours prior to study,including unexplained
fever (temp > 38.1C).

- Autoimmune disease (e.g., systemic lupus erythematosis (SLE), rheumatoid arthritis
(RA), etc.). Patients with a remote history of asthma or mild active asthma are
eligible.

- Other serious medical conditions that may be expected to limit life expectancy to less
than 2 years (e.g., liver cirrhosis) or a serious illness in medical opinion of the
clinical investigator.

- Any condition, psychiatric or otherwise, that would preclude informed consent,
consistent follow-up or compliance with any aspect of the study (e.g., untreated
schizophrenia or other significant cognitive impairment, etc.).

- A known allergy to any component of the HyperAcute® immunotherapy.

- Pregnant or nursing women due to the unknown effects of vaccination on the developing
fetus or newborn infant. (For patients with child bearing potential, a βHCG must be
completed within 14 days of first vaccination).

- Known HIV positive.