Losartan and Hypofractionated Rx After Chemo for Tx of Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer (SHAPER)

Inclusion Criteria:

• Histologically confirmed pancreatic ductal adenocarcinoma

• Borderline resectable or locally advanced unresectable pancreas cancer as defined bythe National Comprehensive Cancer Network (NCCN) and determined by a pancreaticsurgeon prior to therapy. This can be confirmed by the surgeon?s documentation inthe electronic medical record, by a treatment planning conference note, or by thesignature of a pancreatic surgeon

• At least one infusion of FOLFIRINOX, NALIRIFOX, or gemcitabine based chemotherapymust have been attempted.

• No more than 6 months of chemotherapy as defined by standard cycle lengths (everyother week infusions for FOLFIRINOX or NALIRIFOX, and 3 infusions per month forgemcitabine-based therapy). Each infusion of FOLFIRINOX or NALIRIFOX will be countedas 0.5 months. Three infusions of gemcitabine based chemotherapy will be counted as 1 month. If chemotherapy is given over a protracted period, then more than 6 monthsof chemotherapy may be acceptable. For example, if gemcitabine-based therapy isgiven every other week, then each infusion will still only count as 1/3 of a monthtoward the 6 month total. If a partial cycle of chemotherapy is given, that partialcycle will be counted proportional to the amount given. For example, if one of threeplanned infusions of gemcitabine based chemotherapy is given, it will be counted as 1/3 month.

• Enrollment must occur within 90 days of Day 1 of the last infusion given ofchemotherapy. Patients who have primary tumor or regional lymph node progression onchemotherapy or prior to enrollment are eligible if no distant metastases areidentified on the screening imaging assessment.

• Eastern Cooperative Oncology Group (ECOG) performance status =< 1

• Absolute neutrophil count (ANC) >= 1500/uL

• Platelets >= 100k/uL

• Total Bilirubin =< 2.0 mg/dL

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (ULN)

• Serum creatinine < 1.25 md/dL

• Serum potassium < 5.0 mmol/L

• Negative serum or urine pregnancy test at screening for women of childbearingpotential

• Highly effective contraception for both male and female subjects throughout thestudy and for at least 12 months after last study treatment administration if therisk of conception exists

• Recovery to baseline or =< grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments, unless AEs areclinically nonsignificant and/or stable on supportive therapy

• Able to provide informed consent and willing to sign an approved consent form thatconforms to federal and institutional guidelines

Exclusion Criteria:

• Patients with a prior or concurrent malignancy whose natural history or treatmenthas the potential to interfere with the safety or efficacy assessment of theinvestigational regimen of this trial

• Distant metastases. Regional lymphatic disease is acceptable

• Prior radiation therapy or definitive resection for pancreatic cancer

• Uncontrolled gastric or duodenal ulcer disease within 28 days of registration

• Chronic cough, defined 30% of days over 3 months with active symptoms at enrollmentor over 12 months with last active symptoms occurring 6 months prior to enrollment

• Symptomatic hypotension (blood pressure < 90 systolic or < 60 diastolic at screeningvital sign assessment) that has the potential to interfere with the patient's safetyor ability to complete protocol treatment, at the discretion of the treatinginvestigator

• Patients taking > 50mg losartan QD who, at the discretion of the treatinginvestigator, cannot be reduced to the protocol defined regimen.

• Patients taking an angiotensin II receptor blocker or an angiotensin-convertingenzyme inhibitor who, at the discretion of the treating investigator, cannot besafely discontinued prior to Day 1 dosing.

• Patients taking direct renin-angiotensin system inhibitors including aliskiren (Rasilez).

• Prior allergy to an angiotensin II receptor blocker

• Concurrent use of direct renin inhibitor including aliskiren (Rasilez)

• Patients with known history of:

• Heart failure. Patients with heart failure, should have a clinical riskassessment of cardiac function using the New York Heart Association FunctionalClassification. To be eligible for this trial, patients should be class 2B orbetter.

• Patients with a prior history of treatment with cardiotoxic agents should beevaluated for heart failure prior to enrollment at the discretion of thetreating investigator.

• Solitary kidney, renal artery stenosis, or chronic renal failure

• Human immunodeficiency virus (HIV)-infected patients who are not on effectiveanti-retroviral therapy or have a detectable viral load within 6 months of trialentry

• Patients with known evidence of chronic hepatitis B virus (HBV) infection and adetectable HBV viral load

• Patients with a history of hepatitis C virus (HCV) infection who have not beentreated and cured. For patients with HCV infection who are currently on treatment,they are eligible if they have an undetectable HCV viral load

• Subject is currently enrolled on another investigational treatment study forpancreas cancer