Study To Establish Maximum Tolerated Dose (MTD) of Cyberknife in Patients With Un-Resectable Pancreas Cancer (TL002)

The purpose of this study is to determine the MTD for radiosurgery in the treatment of
unresectable pancreas cancer, this MTD can then be used in future phase II or III studies.
In terms of starting dose for the phase I study, based on the low toxicity seen in the
Moffitt study we feel that 30 Gy in five fractions will be a successful starting dose.

Most of the data in unresectable is derived from patients in the metastatic setting in terms
of chemotherapy agents. There have been two major studies that looked at various
chemotherapy regimens versus the previous standard of care Gemzar. One study found improved
survival with FOLFIRINOX and a second found that the combination of nab-paclitaxel and
gemzar were superior to gemzar alone. Thus, the current standard of care for metastatic
pancreas cancer (in which a local therapy like radiation has more limited role) is either
FOLFIRINOX or gemzar and nab-paclitaxel. While there is some discussion of a randomized
study comparing FOLFIRINOX and gemzar combined with nab-paclitaxel such a study has not
started as of this time and it is unclear how much interest there would be in accruing to
this study. Therefore the exact best chemotherapy regimen for metastatic disease is unclear
but is either FOLFIRIONX or gemzar-nab-paclitaxel. The chemotherapy regimens for
unresectable cancer are extrapolated from the metastatic setting, per NCCN guidelines any
chemotherapy regimen approved for metastatic disease is reasonable to use in unresectable
pancreas cancer. Thus for purpose of this study we have chosen one of the two chemotherapy
regimens that have shown the best results in the metastatic setting, since there is no way
to determine the exact best regimen we have chosen gemzar and nab-paclitaxel since it is
felt that this is a less toxic regimen as compared to FOLFIRINOX.

Inclusion Criteria:

- Pathologically confirmed adenocarcinoma of the pancreas

- Unresectable disease based on the following imaging criteria (table 1)

- extrapancreatic extension

- tumor involvement of the SMA or celiac axis

- evidence of occlusion of the SMV-portal vein confluence

- KPS > 50 (ECOG 0-2)

- 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.

- Note that patients with metastatic disease are eligible if it is felt that the
patients will benefit from local control of the primary disease.

- Disease that is measureable or evaluable for response endpoint per RECIST

Exclusion Criteria:

- Prior radiotherapy to the upper abdomen

- Resectable or borderline resectable pancreas cancer. Note that these patients are
eligible for a separate study looking at radiosurgery for borderline resectable
pancreas cancer

- Severe comorbidity rendering a candidate ineligible for chemotherapy or radiation,
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 of childbearing age who are unwilling or unable to practice contraception

- Inability to undergo MRI or CT with contrast for treatment planning

- Patients may not be receiving any other investigational nor commercial agents with
therapeutic intent to treat pancreatic cancer while on this trial. Note that patients
can have had previous investigational therapy but cannot have this concurrently with
this protocol treatment.