GEM+Nab-Paclitaxel Plus Losartan Followed by Stereotactic Radiotherapy for Locally Advanced Pancreatic Cancer

Inclusion Criteria:

1. Patients with histologically or cytologically confirmed pancreatic carcinoma

2. Clinical stage I-III, according to tumor, nodes and metastases (TNM) 8th ed.

3. Locally advanced disease, as defined per National Comprehensive Cancer Network (NCCN) Guidelines version 1.2022 (Appendix D)

4. Baseline systolic blood pressure (SBP) ≥ 100 mmHg (baseline SBP will be documentedduring the enrolment visit in a resting, seated position at least five minutesapart; SBP will be established as the average of the two readings; if SBP isborderline it may be measured in the other arm);

5. Age >18 years and ≤75 years.

6. Life expectancy greater than 12 weeks.

7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2

8. Presence of at least one measurable lesion in agreement to RECIST 1.1 criteria

9. Patients must have normal organ and marrow function as defined below:

10. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence, prior to study entry andcontinuing throughout the study period and for 6 months after final study drugadministration. Should a woman become pregnant or suspect she is pregnant whileparticipating in this study, she should inform her treating physician immediately.

11. Ability to understand and the willingness to sign a written informed consentdocument.

Exclusion Criteria:

1. Clinical stage IV, according to TNM 8th ed.

2. Patients who have previously received chemotherapy or radiotherapy for pancreaticcancer.

3. Participation in another clinical trial with any investigational agents within 30days prior to study screening.

4. History of allergic reactions attributed to compounds of similar chemical orbiologic composition to any agent used in the study.

5. Serious concomitant systemic disorders incompatible with the study (at discretion ofthe investigator);

6. Patient already treated on other Losartan dosages than those prescribed by protocolor treated on other Angiotensin II Receptor Blockers (ARB) therapy for hypertensionor renal protection (with diabetes) at the time of enrolment;

7. Baseline hypotension, defined as systolic BP lower than 100 mmHg on two readingsobtained on two separated days prior to study enrolment.

8. Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliancewith study requirements.