Intra-arterial Gemcitabine vs. IV Gemcitabine and Nab-Paclitaxel Following Radiotherapy for LAPC

All subjects will receive induction therapy of IV gemcitabine plus nab-paclitaxel, as well as
radiation therapy for approximately four months. Subjects who remain eligible will then be
randomized to receive either intra-arterial chemotherapy with gemcitabine; or to continue
gemcitabine plus nab-paclitaxel. Subjects will receive the randomized treatments for up to 16
weeks or until progression. Both groups will receive either IV gemcitabine and nab-paclitaxel
or oral capecitabine following the 16 week treatment course until disease progression at the
discretion of the Investigator.

Inclusion Criteria:

1. Histologically confirmed pancreatic adenocarcinoma with initial diagnosis within 6
weeks of consent

2. Locally advanced, unresectable disease, as defined by NCCN criteria

3. ECOG performance status 0-1

4. Age ≥ 18 years

5. Absolute neutrophil count ≥ 1,500/μL

6. Platelet count ≥ 100,000/μL

7. Hemoglobin ≥ 9.0 g/dL

8. Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects
with creatinine >1.5 mg/dL

9. AST and ALT ≤ 3.0 X the upper normal limit of institution's normal range

10. Total bilirubin ≤ 1.5 X the upper normal limit of institution's normal range

11. PT and PTT must be ≤ 1.5 X upper normal limit of institution's normal range

12. INR ≤ 1.5

13. Life expectancy > 12 weeks

14. Women of childbearing potential must have a negative serum or urine pregnancy test
within 1 day prior to administration of the first dose of chemotherapy

15. Provide written informed consent

16. Subjects willing to participate in the study for at least 8 months

Exclusion Criteria:

1. Any prior treatment for pancreatic cancer

2. Any evidence of metastatic disease or another active malignancy within the past two
years except for cervical cancer in situ, in situ carcinoma of the bladder or
non-melanoma carcinoma of the skin.

3. Prior biliary bypass surgery

4. Subjects unable or unwilling to have their first randomized treatment within three
weeks of the post induction imaging and within five weeks of their last induction
treatment

5. Subjects without baseline tumor imaging

6. Stenosis or occlusion in intended artery for treatment that precludes IA therapy as
determined by CT or MRI

7. Tortuosity preventing the delivery of the guide sheath and or RenovoCath™ catheter to
intended site as determined by CT or MRI

8. Inability to exclude major side branches in the area of the intended RenovoCath™
occlusion as determined by CT or MRI

9. No suitable artery with a diameter greater than 4mm in proximity of at least one side
of the tumor as determined by CT or MRI

10. Subjects with known HIV or active viral hepatitis

11. Severe infections within 4 weeks prior to the first study treatment, including but not
limited to hospitalization for complications of infection, bacteremia or severe
pneumonia

12. Signs or symptoms of infection within 2 weeks prior to the first study treatment

13. Received oral or IV antibiotics for an infection within 2 weeks prior to the first
study treatment. Subjects receiving prophylactic antibiotics are eligible

14. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
gemcitabine or nab-paclitaxel

15. Any anti-cancer therapy including chemotherapy, hormonal therapy, or radiotherapy
within 2 weeks prior to initiation of study treatment; or herbal therapy intended as
anti-cancer therapy within 1 week prior to initiation of study treatment

16. Subjects with uncontrolled seizures

17. Cardiovascular disease including unstable angina; therapy for life-threatening cardiac
arrhythmia, myocardial infarction, stroke; or NYHA Class III or IV congestive heart
failure within the last 3 months prior to initiation of study treatment

18. Life-threatening visceral disease or other severe concurrent disease

19. Any major surgery within 4 weeks, minor surgery within 2 weeks or other minor
procedures requiring light sedation, such as endoscopies or mediport placement, within
48 hours prior to initiation of study treatment

20. Women who are breastfeeding

21. Male or female subjects of reproductive potential who do not agree to employ two
highly effective and acceptable forms of contraception throughout their participation
in the study and for 90 days after the last study treatment

22. Subjects concurrently receiving any other investigational agents within 2 weeks prior
to the first study treatment

23. Any psychiatric illness or social situations that would limit compliance with study
requirements