Induction Gemcitabine/Capecitabine Followed by SBRT in Pancreatic Adenocarcinoma A Prospective Evaluation in Patients With Locally Advanced Pancreas Cancer

Trial Information

Induction Gemcitabine/Capecitabine Followed by SBRT in Pancreatic Adenocarcinoma A Prospective Evaluation in Patients With Locally Advanced Pancreas Cancer

All subjects will have a baseline CT or FDG-PET/CT prior to initiation of therapy. This will
be done at the Hillman or in Radiation Oncology. Enrolled patients will undergo appropriate
lab work and staging as described

1. Albumin, alkaline phosphatase, glucose, electrolytes

2. Ca 19-9 and CEA

3. Due to an interaction of capecitabine and oral coumadin-derivative anticoagulants and
risk of bleeding/thrombotic events, if a patient is on coumadin, frequent monitoring of
INR and dose adjustments of anticoagulants must be exercised during protocol treatment.
Alternatively, low molecular weight heparin may be substituted for oral anticoagulants
Chemotherapy will be initiated consisting of gemcitabine 1000mg/m2 IV on day 1 and 8 of
a 21 day cycle. Dosage for gemcitabine is described below using the Body surface area
(BSA).

BSA will be calculated from body weight in kg, recorded prior to every gemcitabine dosing,
and height in cm, recorded at baseline.

Premedication for Gemcitabine

A standard, FDA-approved antiemetic medication will be administered to study participants at
the discretion of the treating oncologist (investigator) one-half hour prior to the
gemcitabine infusion. Examples of standard antiemetics include ondansetron (Zofran),
granisetron (Kytril), dolasetron (Anzemet), compazine, and dexamethasone. The dosage and
route of administration will be determined by the treating oncologist based upon the given
clinical scenario.

In addition, capecitabine 650mg/m2 PO will be taken twice daily on days 1-14 of a 3 week
cycle. Four cycles total (12 weeks) of chemotherapy will be given. Dosage for capecitabine
is described below using the Body surface area (BSA).

BSA will be calculated from body weight in kg, recorded prior to every capecitabine dosing,
and height in cm, recorded at baseline.

Capecitabine (Xeloda; F. Hoffmann-La Roche AG, Basel, Switzerland) is supplied as film-coated
tablets in two dose strengths (150 and 500 mg); the closest practical dose (by rounding up
or down) calculated on body-surface area based on a combination of tablets is taken within
30 minutes after the end of a meal.

Patients will be assessed during chemotherapy with appropriate dose modifications made based
on toxicity. Following the completion of chemotherapy, a new FDG-PET/CT or CT will be
obtained to assess response and plan for SBRT. For those patients with SD, PR, or CR, SBRT
will be planned and delivered.

Fidiucial placement In addition, all patients will have fiducial markers placed for
localization at time of SBRT. Three to five soft-tissue fiducials (markers) will be placed
in and/or around the tumor, at least 1cm apart. Oftentimes, these are placed at the time of
endoscopic ultrasound and biopsy for diagnosis. If that is not the case, patients will be
scheduled for a repeat EUS and have the markers placed prior to CT or FDG-PET/CT simulation.
Alternatively, fiducials may be placed at the time of staging laparoscopy.

Stereotactic Body Radiotherapy Planning SBRT will be done in Shadyside Radiation Oncology.

An SBRT plan will be created based on the disease contoured on the CT and PET. The plan will
be to deliver fractionated SBRT to the isodose line best encompassing the PTV:

12 Gy x 3 fractions (36 Gy total)

Careful evaluation of the each plan will be conducted by the radiosurgical team to ensure
that normal tissues and critical structures tolerances are maintained.

The maximum dose (in Gy) within the treatment volume (MD), prescriptions dose (PD), and the
ratio of MD/PD (as a measure of heterogeneity within the target volume), prescription
isodose volume (PIV in mm3), tumor volume (TV in mm3), and the ratio of PIV/TV (as a measure
of dose conformity of the treatment relative to the target) will be recorded.

Quality of Life Assessment Quality of life assessment using the Functional Assessment of
Cancer Therapy - General (FACT-G) tool, which is a validated tool, will be administered to
all subjects prior to treatment and at each follow-up visit.

For patients with potentially resectable tumors, they will be assessed 10 - 12 weeks after
SBRT by a multidisciplinary team including two expert pancreas surgeons and by FDG-PET/CT or
CT scan. If deemed appropriate, patients with an adequate response will be taken for
surgical resection. This will be performed as standard care.

Time frames for chemotherapy and SBRT for 4 cycles of gemcitabine and capecitabine. The SBRT
will not start until twelve weeks after the chemotherapy stops and will last approximately
one week. Each cycle of gemcitabine and capecitabine is three weeks. Upon completion of
treatment patients will be followed for survival for 24 months. They will be in the study
for approximately two years give or take a few months.

Interim medical history and physical examination 4 - 6 weeks after SBRT.

Serum chemistry and electrolytes to include BUN, creatinine, sodium, potassium, bicarbonate,
chloride, calcium, magnesium, glucose, total bilirubin, AST, ALT, alkaline phosphatase prior
to chemotherapy treatments, 4 -6 weeks post-SBRT treatment, and then at follow-up as
clinically indicated

Hematologic studies to include CBC with differential and platelet count weekly during
chemotherapy sessions and then repeated 4-6 weeks post-SBRT treatment and then at follow-up
as clinically indicated

CT or FDG-PET/CT scans (for consistency procedure done at screening/planning will continue
in follow-up) will be obtained at 10-12 weeks post-treatment and will be reviewed for
evidence of response. Subjects who demonstrate no evidence of distant metastases and meet
RECIST criteria of partial response, complete response, or stable disease will be offered
surgical exploration and attempted curative resection. Subjects demonstrating unresectable
disease or progression of disease will be started on systemic chemotherapy at the discretion
of the treating medical oncologist.