Radiopaque Hydrogel in Patients Undergoing Radiotherapy for Pancreatic Cancer

Pancreatic ductal adenocarcinoma is now the third leading cause of cancer-related death, with
a devastating 5-year overall survival (OS) rate of nearly 8%, despite having the 12th most
common incidence of all malignancies in the United States. One-third of patients will present
with borderline resectable or unresectable, locally advanced pancreatic cancer (BR/LAPC). In
the cases of LAPC, chemotherapy with or without radiation may be recommended to improve the
quality of life by relieving symptoms and extending survival. Despite aggressive combined
modality therapy, the median survival remains between 9 and 15 months.

Current guidelines for the management of BR/LAPC patients include single- or multi-agent
chemotherapy or chemoradiation (CRT) in sequence with chemotherapy. Results of studies
comparing chemotherapy alone to CRT for patients with BR/LAPC are mixed. The importance of
local control or delaying local progression on improving morbidity and possibly mortality in
patients with pancreatic cancer is supported by autopsy data demonstrating that 30% of
patients die of locally destructive disease. It follows that in the cases of LAPC, advanced
radiation therapy techniques using dose-escalation with intensity modulated radiotherapy
(IMRT) and stereotactic body radiotherapy (SBRT) are potential strategies to improve local
control.

A consistent challenge to dose-escalation with IMRT (intensity modulation radiation therapy)
or SBRT is the sensitivity of the surrounding gastrointestinal organs, particularly the small
bowel which is directly adjacent to the head of the pancreas head of the pancreas (HOP). For
BR/LAPC patients treated with CRT, advances in image guidance have provided the opportunity
to safely deliver higher biologically effective doses of radiation therapy using IMRT of >70
Gy (57.25 Gy in 25 fractions, BED 70.36 Gy) compared to standard fractionation regimens
(50.40 Gy in 28 fractions or 50 Gy in 25 fractions, BED 59.47 Gy and 60 Gy, respectively).
Those patients who underwent dose-escalated CRT with BED>70 Gy, did have a superior OS
compared to those receiving BED<70 Gy, supporting the utility of dose-escalation in improving
long-term outcomes. SBRT involves a short course of radiation therapy, five fractions or
less, and has demonstrated higher rates of local control compared to CRT in other disease
sites. Early studies evaluating SBRT for pancreatic cancer utilized single fractions of 25
Gy, resulting in local control rates of 100% at 1 year but unacceptably high rates of
gastrointestinal toxicity. More recently, hypofractionated SBRT (33 Gy total, 6.6 Gy daily
fractions) has been evaluated and utilized by our group in an effort to reduce the toxicity
of therapy, with results demonstrating nearly 80% rate of freedom from local progression at
one year and an acceptable 11% long-term gastrointestinal toxicity. Outcomes with SBRT are
thus promising; however, higher local control rates with dose-escalation may be achievable,
but current practice is limited due to risks of toxicity.

The goal of this pilot imaging study is to evaluate the visibility of marking the interface
between the pancreas and duodenum with TraceIT Tissue Marker. Patients with a pathologically
confirmed diagnosis of BR/LAPC pancreatic adenocarcinomas indicated for neo-adjuvant
image-guided radiotherapy with SBRT will be enrolled. This study will thus set the stage for
further investigations using the TraceIT Tissue Marker to avoid duodenum toxicity with
imaging localization, enabling further dose intensification with SBRT or IMRT to improve the
clinical outcomes in BR/LAPC.

Inclusion Criteria:

1. Age ≥18 years old

2. BR/LAPC pancreatic carcinoma disease

3. Radiotherapy or chemoradiotherapy for treatment of the disease is indicated with the
intent for eventual surgical resection

4. Subjects Screening/Baseline laboratory testing must meet the following laboratory
value criteria:

1. White blood cell count: ≥ 3.0 x 109/L

2. Absolute neutrophil count (ANC): ≥ 1.5 x 109/L

3. Platelets: ≥ 100 x 109/L

4. Total bilirubin: ≤ 2.0 times upper limit of normal (ULN)

5. AST (Aspartate Aminotransferase) and ALT (Alanine Aminotransferase): ≤ 3.0 times
institutional upper normal limit

6. Serum creatinine: 1.5 times ULN (upper limit of normal)

7. INR (international normalized ratio): < 1.5

8. Serum pregnancy: Negative

9. Hemoglobin: ≥ 8.0 g/dl

5. Zubrod Performance Status 0-2

6. Subject or authorized representative, has been informed of the nature of the study and
has provided written informed consent, approved by the appropriate Institutional
Review Board (IRB) of the respective clinical site.

Exclusion Criteria:

1. Previous thoracic radiotherapy

2. Any GI (gastrointestinal) abnormality that would interfere with the ability to access
the injection site

3. Active gastroduodenal ulcer or watery diarrhea

4. Active bleeding disorder or a clinically significant coagulopathy defined as a PTT
(Partial thromboplastin time) >35s or INR>1.4 or platelet count less than 100,000 per
mm3.

5. Active inflammatory or infectious process involving the gastrointestinal tract based
on positive diagnosis or suspected diagnosis in the presence of fever>38°C or
WBC>12,000/uL.

6. Compromised immune system: WBC (white blood count) <4000/uL or >12,000/uL.

7. History of Chronic Renal Failure.

8. Documented history of uncontrolled diabetes (i.e., symptomatic hyperglycemia that
cannot be medically managed, fasting blood glucose level above 300 mg/dL, and/or
frequent swings between hyperglycemia and hypoglycemia)

9. Currently enrolled in another investigational drug or device trial that clinically
interferes with this study.

10. Unable to comply with the study requirements or follow-up schedule.

11. Any condition or comorbidity that the Investigator believes would interfere with the
intent of the study or would make participation not in the best interest of the
subject.

12. Pregnancy, breast-feeding, women of child-bearing age must use contraceptives