Liposomal Irinotecan Plus 5-FU / LV Combined With Paricalcitol in Patients With Advanced Pancreatic Cancer Progressed on Gemcitabine-based Therapy

Inclusion Criteria:

- Histologically or cytologically confirmed pancreatic adenocarcinoma.

- Must have progressed on or become intolerant to gemcitabine-containing therapy in the
advanced setting (not resectable).

- Measurable disease defined as lesions that can be accurately measured in at least one
dimension (longest diameter to be recorded) as ≥ 10 mm with CT scan, as ≥ 20 mm by
chest x-ray, or ≥ 10 mm with calipers by clinical exam.

- At least 18 years of age.

- Life expectancy > 3 months.

- ECOG performance status ≤ 1

- Normal bone marrow and organ function as defined below:

- Absolute neutrophil count ≥ 1,500/mcL

- Platelets ≥ 100,000/mcL

- Hemoglobin ≥ 9 g/dL

- Total bilirubin ≤ 1.5 x ULN

- Serum albumin > 3g/dL

- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN unless there are liver metastases, in which case
AST and ALT ≤ 5.0 x IULN

- Creatinine ≤ 1.5 x IULN OR GFR > 50 mL/min

- Corrected serum calcium < 10.3 mg/dL

- Serum phosphorus ≤ 4.5 mg/dL

- Patients will require a 2-week washout period from previous gemcitabine-based systemic
therapy prior to the first planned dose of study treatment.

- Prior treatment-related toxicity must recover to grade 1 or less prior to the first
planned dose of study treatment.

- 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 for
the duration of study participation. Should a woman become pregnant or suspect she is
pregnant while participating in this study, she must inform her treating physician
immediately.

- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

- Patients with active renal, ureteral, or bladder stones on the screening imaging.

- Current use of or anticipated need for alternative, holistic, naturopathic, or
botanical formulations used for the purpose of cancer treatment.

- A history of other malignancy within 2 years previous, with the exception of those
basal cell or squamous cell carcinoma of the skin which were treated with local
resection only, or carcinoma in situ of the cervix.

- Currently receiving any other investigational agents.

- Patients who received FOLFIRINOX or FOLFIRI in the neoadjuvant or adjuvant setting who
experienced disease recurrence within 6 months will be excluded (patients who received
5-FU or capecitabine as a radiosensitizer are permitted to enroll.)

- Patients with known active/ progressive brain metastases or leptomeningeal involvement
will be excluded due to their poor prognosis. Patients with treated/stable brain
metastases, defined as patients who have received prior therapy for their brain
metastases and whose CNS disease is radiographically stable at study entry, are
eligible.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to paricalcitol, liposomal irinotecan, 5-FU, LV, or other agents
used in the study.

- Clinical significant ascites that requires therapeutic paracentesis or significant
pleural effusion that requires therapeutic thoracentesis.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
arrhythmia.

- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 7 days of study entry.

- Known HIV-positivity not on anti-retroviral therapy, or with CD4+ T cell count <
200/ul (patients with known HIV currently on anti-retroviral therapy with CD4+ T cell
count > 200/ul will be included).