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

Inclusion Criteria: Patients with histologically or cytologically confirmed pancreatic carcinoma Clinical stage I-III, according to tumor, nodes and metastases (TNM) 8th ed. Locally advanced disease, as defined per National Comprehensive Cancer Network (NCCN) Guidelines version 1.2022 (Appendix D) Baseline systolic blood pressure (SBP) ≥ 100 mmHg (baseline SBP will be documented during the enrolment visit in a resting, seated position at least five minutes apart; SBP will be established as the average of the two readings; if SBP is borderline it may be measured in the other arm); Age >18 years and ≤75 years. Life expectancy greater than 12 weeks. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Presence of at least one measurable lesion in agreement to RECIST 1.1 criteria Patients must have normal organ and marrow function as defined below: Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence, prior to study entry and continuing throughout the study period and for 6 months after final study drug administration. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Clinical stage IV, according to TNM 8th ed. Patients who have previously received chemotherapy or radiotherapy for pancreatic cancer. Participation in another clinical trial with any investigational agents within 30 days prior to study screening. History of allergic reactions attributed to compounds of similar chemical or biologic composition to any agent used in the study. Serious concomitant systemic disorders incompatible with the study (at discretion of the investigator); Patient already treated on other Losartan dosages than those prescribed by protocol or treated on other Angiotensin II Receptor Blockers (ARB) therapy for hypertension or renal protection (with diabetes) at the time of enrolment; Baseline hypotension, defined as systolic BP lower than 100 mmHg on two readings obtained on two separated days prior to study enrolment. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.