A Study of Pre-Operative Cyberknife in Patients With Potentially Resectable Pancreas Cancer

This study is evaluating the role of neoadjuvant chemotherapy and CyberKnife therapy in
increasing the number of patients who are able to successfully undergo definitive surgical
management of their pancreatic carcinoma. In addition, we will evaluate the associated
therapeutic toxicities and gather data regarding the quality of life indicators at similar
time intervals for an improved overall assessment of the effects of this course of treatment
on our patients.

Surgery is deemed the only curative technique for pancreatic cancer. Unfortunately, more
than 80% of patients who present with the disease cannot be cured by resection.

The literature reports median survival for resectable patients on the order of 19 months,
with a 20% 5 year survival rate. For patients unable to undergo surgical resection, the
median survival in the literature is approximately 11 months. In the absence of the proposed
protocol, this patient population would be treated as per the standard of care for locally
advanced non-metastatic surgically unresectable pancreatic malignancies, which would include
a combination of chemotherapy and radiation therapy. The anticipated Grade 4 and above
toxicity would be approximately 3-5% from this regimen. The rate of G 4 and above toxicity
is not known with the use of this neoadjuvant regimen, and, therefore, this constitutes the
major risk associated with this protocol therapy. The associated benefit, however, is the
anticipated improvement in median survival that these patients may derive from the ability
to successfully undergo surgical resection. A secondary proposed benefit is the potential
for reduction in the treatment associated toxicity with this altered multimodality schedule
when compared to traditional multimodality care or non-surgical care of locally advanced
pancreatic malignancy.

Inclusion Criteria:

- Pathologically confirmed adenocarcinoma of the pancreas

- Resectable or potentially resectable disease based on the following imaging criteria
performed < 4 weeks from study entry and as determined by local review (Cooper
radiologist)

- No extrapancreatic extension to nearby organs (ie; small bowel)

- No SMV/PV >180 degree involvement and/or reconstructable (as determined by
Surgeon) occlusion

- No SMA Abutment TVI<180 degrees

- No Celiac trunk abutment Total volume involved < 180 degrees

- Note that both resectable and potentially resectable patients are eligible

- ECOG ≤ 2

- Adequate hematologic and end organ function as defined by

- Hepatic transaminase levels < 3 x normal

- Total bilirubin < 5 mg/dl (if stented)

- Serum creatinine level < 1.6 mg/dl

- Absolute neutrophil count > 1,500cells/mm3

- Platelet count > 100,000 cells/mm3

- Medical status suitable for consideration of major pancreatic surgery

- Age >18 years

- Women of childbearing age and male participants must practice adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to and throughout
study treatment.

- Life expectancy > 3 months

- Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

- Prior invasive malignancy within 5 years other than pancreatic adenocarcinoma

- Prior radiotherapy to the upper abdomen

- Severe comorbidity rendering a candidate ineligible for surgical resection

- Local, regional or distant extrapancreatic disease

- Patients of childbearing age who are unwilling or unable to practice contraception

- Failure to meet any of the above eligibility criteria

- Inability to undergo MRI with contrast for treatment planning

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements.

- Patients may not be receiving any other investigational nor commercial agents with
therapeutic intent to treat pancreatic cancer while on this trial.

- unresectable pancreatic cancer based on the following imaging criteria performed < 4
weeks from study entry and as determined by local review (Cooper radiologist)

- Extrapancreatic extension to nearby organs (ie; small bowel)

- SMV/PV >180 degree involvement and/or reconstructable (as determined by Surgeon)
occlusion

- SMA Abutment TVI<180 degrees

- Celiac trunk abutment Total volume involved < 180 degrees

- Distant metastases