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

Inclusion Criteria:

1. Histologically or Cytopathology confirmed pancreatic adenocarcinoma with initialdiagnosis within 8 weeks of consent for patients who enroll at cycle 1, and from thestart of cycle 1 of gemcitabine + nab-paclitaxel chemotherapy for patients whoenroll at cycle 2

2. Locally advanced, unresectable disease at screening and prior to randomization, asdefined by NCCN criteria determined by an on-site, experienced, multidisciplinaryteam (as confirmed by CT or MRI within 30 days of the start of cycle 1)

3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1

4. Age ≥ 18 years

5. Adequate laboratory values prior to receiving the first dose of nab-paclitaxel andgemcitabine: (criterion must be met prior to cycle 2.) For a subject with elevatedbilirubin, AST or ALT, who has had a biliary stent placed, if the subject's labvalues have returned to within the required range for eligibility noted below insub-criteria e and f [(AST) ALT ≤ 3.0 X the upper normal limit, and total bilirubin ≤ 1.5 X the upper normal limit] after placement of stent and prior to cycle 2,he/she is eligible for the study. Additional details regarding eligibility forsubjects who have had biliary stents recently placed are outlined in sub-criteria fand h below.

6. Absolute neutrophil count (ANC) ≥ 1,500/μL

7. Platelet count ≥ 100,000/μL

8. Hemoglobin ≥ 9.0 g/dL

9. Serum creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 50 mL/min/1.73 m2 forsubjects with creatinine >1.5 mg/dL

10. *Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 X the uppernormal limit of institution's normal range

11. *Total bilirubin ≤ 1.5 X the upper normal limit of institution's normal range -OR- If biliary stent is placed or planned to be placed within 6 weeks of Cycle 1 Day 1 (C1D1), total bilirubin ≤ 2.0 X the upper normal limit of institution'snormal range (see section 9.1.4 for dose modification due to elevatedbilirubin)

12. Prothrombin time (PT) and partial thromboplastin time (PTT) must be ≤ 1.5 Xupper normal limit of institution's normal range. Subjects who are currentlytaking anti-coagulant therapy are eligible if not meeting this criterion

13. International normalized ration (INR) ≤ 1.5 X upper normal limit ofinstitution's normal range. Subjects who are currently taking anti-coagulanttherapy are eligible if not meeting this criterion *For elevated AST, ALT, andtotal bilirubin at screening, subject must have a normalized result prior toinitiation of Cycle 2 if abnormal labs are considered related to bile ductobstruction and a biliary stent has been placed

14. Life expectancy > 12 weeks

15. Negative pregnancy test for women of childbearing potential (either serum or urine)within one day prior to administration of the first dose of chemotherapy. Women ofchildbearing potential should use highly effective methods of contraception duringtreatment and for up to 6 months following treatment cessation

16. Provide written informed consent

17. Subjects willing to participate in the study for at least 8 months if randomized toIA gemcitabine OR IV gemcitabine + nab-paclitaxel

Exclusion Criteria:

1. Any prior treatment for pancreatic cancer OR more than one cycle of gemcitabine andnab-paclitaxel treatment. For subjects who have started on their first cycle ofgemcitabine and nab-paclitaxel treatment prior to consent, Inclusion Criterion #1only applies to the first gemcitabine and nab-paclitaxel dose and must be within 6weeks of confirmed diagnosis

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

3. Subjects unable or unwilling to have their first randomized treatment within 3 weeksof the post induction imaging and within 5 weeks of their last induction treatment

4. Subjects without baseline tumor imaging

5. As determined by the Sponsor: Arterial anatomy unsuitable for IA delivery of gemcitabine to the intended tumorsite, determined by CT or MRI, as determined and approved by the Sponsor ImagingAdvisor, which includes the following:

6. Stenosis or occlusion in the intended artery for treatment

7. Inability to exclude major side branches in the area of the intendedRenovoCath® catheter occlusion

8. No suitable artery with a diameter greater than 3 mm in proximity of at leastone side of the tumor

9. Superior mesenteric vein (SMV) occlusion or stenosis that cannot be resolvedwith medication or intervention prior to randomization, if the superiormesenteric artery (SMA) is the only viable treatment artery Note: ArterialAnatomy will be reviewed by the Sponsor, RenovoRx Imaging Advisor, and RenovoRxMedical Monitor for approval

10. Contraindications for SBRT planning which includes the following:

11. Gastrointestinal mucosal infiltration evident at the time of diagnosticendoscopy

12. Prior abdominal radiotherapy judged to have clinically significant degree ofoverlap with planned SBRT dose distribution Note: Primary tumors with adiameter greater than 7 cm must be assessed on a case-by-case basis with theRenovoRx Imaging Advisor prior to excluding the subject from the trial.

13. Subjects with known HIV infection or active viral hepatitis

14. Severe infections requiring hospitalization within 4 weeks prior to the first studytreatment, including but not limited to complications of infection, bacteremia orsevere pneumonia

15. Signs or symptoms of infection within 2 weeks prior to the first study treatment, asassessed by the Investigator

16. Received antibiotics for treatment of an infection within 48 hours prior toinitiation of study treatment. Subjects receiving prophylactic antibiotics areeligible

17. History of severe allergic, anaphylactic, or other hypersensitivity reactions togemcitabine or nab-paclitaxel

18. Any anti-cancer therapy including chemotherapy, hormonal therapy for prostatecancer, or radiotherapy within 2 weeks prior to initiation of study treatment; orherbal therapy intended as anti-cancer therapy within 1 week prior to initiation ofstudy treatment

19. Subjects with uncontrolled seizures

20. Cardiovascular disease including unstable angina or life-threatening cardiacarrhythmia, myocardial infarction, stroke; or New York Heart Association (NYHA)Class III or IV congestive heart failure (CHF) within the last 3 months prior to thefirst study treatment. Subjects with prior history of Myocardial Infarction (MI),congestive heart failure (CHF), coronary artery bypass grafting, or prior valvesurgery need to have assessment of ejection fraction (EF) to ensure EF is not ≤ 40% (as determined by MRI, ECHO, or Nuclear Scan), within the last 3 months prior to theinitiation of study treatment

21. Other severe concurrent disease or comorbidities which make it difficult toparticipate in this study, as assessed by Investigator

22. Any of the following procedures prior to initiation of study treatment:

23. Catheterization, endoscopy, stent or drain placement within 48 hours. (Diagnostic laparoscopy without surgical intervention and/or port placement donot require any wait time prior to study treatment)

24. Minor surgery requiring light sedation (such as surgical laparoscopy) within 2weeks

25. Major surgery within 4 weeks

26. Women who are breastfeeding

27. Male or female subjects of reproductive potential who do not agree to either remainabstinent or employ highly effective and acceptable forms of contraceptionthroughout their participation in the study and for 6 months after the last studytreatment

28. Subjects receiving any other investigational agents within 2 weeks prior to theinitiation of treatment

29. Any social situations or psychiatric illness that would limit compliance with studyrequirements

30. Subjects unable or unwilling to have standard catheterization procedure