PHL Treatment in Pancreatic Cancer

Inclusion Criteria for all study participants:

* Patients must have new diagnosed histologically or cytologically confirmed pancreatic adenocarcinoma.
* Patients must have resectable non-metastatic PDAC and anticipate receiving surgery in a minimum of 4 weeks and a maximum of 12 weeks from completing neoadjuvant chemotherapy and radiation.
* Patients are planned for a minimum of 3 months of modified FOLFIRINOX treatment followed by chemo/radiation followed by surgical resection.
* Age \> 18 years.
* ECOG performance status 0-1
* Patients must have normal organ function as defined below
* Total bilirubin within normal institutional limits
* AST/ALT (SGOT/SGPT) \< 5 times institutional normal limits
* Creatinine within normal institutional limits OR
* Creatinine clearance \> 30 Ml/min/1.73 m2 for patients with creatinine levels above institutional normal
* Women of childbearing potential must be non-pregnant (negative pregnancy test within 72 hours prior to registration). Postmenopausal woman must have been amenorrhoeic and nonlactating for at least 12 months to be considered of non-childbearing potential. Men and women of child bearing potential must be willing to exercise an effective form of birth control (abstinence/contraception) while on study and for 3 months after therapy is completed.
* Ability to understand and willingness to sign a written informed consent and HIPAA consent document

Exclusion Criteria for all study participants:

* Tumors of acinar or adenocarcinoma histology
* Patients may not be receiving any other investigational agents
* Patients currently receiving hydroxychloroquine or an angiotensin II receptor blocker
* Patients with radiological or cytologically confirmed metastatic or unresectable disease
* Pregnant or breast feeding. Refer to section 4.4 for further detail.

Inclusion criteria for participation in experimental PHL therapy (Arm A):

* Patients must have resectable non-metastatic PDAC and anticipate receiving surgery in a minimum of 4 weeks and a maximum of 12 weeks from completing neoadjuvant chemotherapy and chemoradiation.
* Patients completed a minimum of 3 months of modified FOLFIRINOX treatment followed by chemoradiation prior to study enrollment and plans for surgical resection.
* Ability to understand and willingness to sign a written informed consent and HIPAA consent document

Exclusion Criteria for participation in Experimental PHL Therapy (Arm A):

* Patients who have residual grade 3 or higher adverse events from prior chemotherapy or chemoradiotherapy for pancreatic cancer
* Concomitant use of an ACE inhibitor or ARB, vitamin D, or hydroxychloroquine. Patient may elect to stop Vitamin D supplement and will be allowed to enroll on the study.
* Patients cannot have a history of retinopathy, macular degeneration or other severe ocular issues, baseline hypotension (systolic blood pressure lower than 100 mmHg on two separate readings obtained on two separate days), or history of hypercalcemia requiring treatment
* Patients with known disorders precluding use of any of the study drugs including a history of angioedema, hypotension, or renal disease (CrCl \< 30mL/min).
* History of allergic reactions attributed to compound of similar chemical or biologic composition to the agent(s) used in this study
* Patients receiving any medications or substances that significantly interact with PHL are ineligible (specified in section 5.2).
* A marked baseline prolongation of QT/QTc interval
* A history of additional risk factors for Torsades de Pointes (e.g., heart failure, family history of Long QT Syndrome)
* Atrio-ventricular blockade of 2nd or 3rd degree
* 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.
* Pregnant or breast feeding.