Paricalcitol, Hydroxychloroquine, and Losartan for the Modification of Pancreatic Tissue before Surgery in Patients with Resectable, Non-Metastatic Pancreatic Ductal Cancer

Inclusion Criteria

• Patients must have new diagnosed histologically or cytologically confirmed pancreatic adenocarcinoma
• Patients must have resectable non-metastatic pancreatic ductal adenocarcinoma (PDAC) and anticipate receiving surgery in a minimum of 2 weeks and a maximum of 12 weeks from completing neoadjuvant chemotherapy +/- radiation
• Patients are planned for or completed minimum of 3 months of chemotherapy as per treating physician’s choice, which could be followed by chemo/radiation if deemed necessary by the treating team and is planned for surgical resection
• Age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Patient must have adequate organ function as determined by treating physician and recovered all treatment related toxicities to grade 2 or less
• 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 Health Insurance Portability and Accountability Act (HIPAA) consent document
• ARM A: Patients must have resectable non-metastatic PDAC and anticipate receiving surgery in a minimum of 2 weeks and a maximum of 12 weeks from completing neoadjuvant chemotherapy +/- chemoradiation
• ARM A: Patients completed a minimum of 3 months total of chemotherapy as per treating physician’s choice with or without chemoradiation prior to study enrollment and plans for surgical resection
• ARM A: Ability to understand and willingness to sign a written informed consent and HIPAA consent document

Exclusion Criteria

• 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
• ARM A: Patients who have residual grade 3 or higher adverse events from prior chemotherapy or chemoradiotherapy for pancreatic cancer
• ARM A: Concomitant use of an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blockers (ARB), vitamin D, or hydroxychloroquine. Patient may elect to stop Vitamin D supplement and will be allowed to enroll on the study
• ARM A: 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
• ARM A: Patients with known disorders precluding use of any of the study drugs including a history of angioedema, hypotension, or renal disease (creatinine clearance [CrCl] < 30mL/min).
• ARM A: History of allergic reactions attributed to compound of similar chemical or biologic composition to the agent(s) used in this study
• ARM A: Patients receiving any medications or substances that significantly interact with PHL are ineligible
• ARM A: A marked baseline prolongation of QT/corrected QT (QTc) interval defined as a QTc >= 470 ms for males, and >= 480 ms for females * Framingham formula: QTc = QT + 0.154 (1-RR interval)
• ARM A: A history of additional risk factors for Torsades de Pointes (e.g., heart failure, family history of Long QT Syndrome)
• ARM A: Atrio-ventricular blockade of 2nd or 3rd degree
• ARM A: 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
• ARM A: Pregnant or breast feeding