Pembrolizumab (also known as Keytruda®), which is approved in the USA and some other
countries, is available by prescription to treat several different cancers, but has not been
approved to treat pancreatic cancer. Pembrolizumab helps the body detect and fight cancer by
making cancer cells more vulnerable to attack by the body's immune system. This medication
binds to and lessens the action of specific parts of cells in the body's immune system, which
act to modulate or balance the immune response. By decreasing this modulation of the immune
response, the body's own system may be better able to fight the cancer. Pembrolizumab is
known as an immune checkpoint inhibitor.
It is thought that the effect of pembrolizumab could possibly be strengthened by the addition
of paricalcitol, which is a form of vitamin D. Paricalcitol may make the cells in the immune
system more sensitive to the activity of pembrolizumab and could make the local environment
hostile to the cancer cells. Both activities could be effective against cancer growth.
Paricalcitol (also known as Zemplar®) is used to treat high levels of parathyroid hormone and
prevent bone loss in patients with advanced kidney disease. Paricalcitol is not approved by
the FDA for the treatment of advanced pancreatic cancer.
The effects of the study drugs will be assessed by repeated radiological imaging (CT scans),
incidence of adverse reactions, and survival rates.
Participants will also be asked to provide biological specimens for the study team to measure
cellular changes. This will include fecal matter (stool), blood, and tumor tissue.
The Food and Drug Administration (FDA) has determined that this study meets the requirements
for Investigational New Drug (IND) Exemption.
Inclusion Criteria:
1. Be willing and able to provide written informed consent for the trial.
2. Be ≥ 18 years of age on day of signing informed consent.
3. Histologically or cytologically confirmed pancreatic adenocarcinoma with metastasis,
who had obtained a best response of at least stable disease (SD) or a partial response
(PR) for a period of 2 months with no further shrinkage of ≥ 30% on scan on their
first line of chemotherapy for their advanced metastatic disease. Note: Patients that
have had prior chemotherapy as adjuvant or neoadjuvant therapy are permitted.
4. Have a performance status of 0 or 1 on the ECOG performance scale.
5. Able to submit an archival tumor specimen (primary or metastatic site) and a
discussion is documented with trial investigator at screening that patient will
consider providing tissue from a newly obtained core or excisional biopsy of a tumor
lesion at baseline and a second biopsy 9 weeks after starting trial treatment, unless
tumor is considered inaccessible or biopsy is otherwise considered not in the patients
best interest. Participation in this trial is not contingent on patient consenting to
optional tumor biopsies.
6. Demonstrate adequate organ function as defined in protocol, AND serum corrected
calcium value must be ≤ Institutional ULN and ≥ 8.0 mg/dL, and phosphorus levels must
be ≤ Institutional ULN and ≥ 2.5 mg/dL.
7. Female participants of childbearing potential should have a negative serum pregnancy
test within 24 hours prior to receiving first dose of trial medication.
8. A female participant is eligible to participate if she is not pregnant , not
breastfeeding, and at least one of the following conditions applies:
1. Not a woman of childbearing potential (WOCBP) as defined in protocol
OR
2. A WOCBP who agrees to follow the contraceptive guidance in protocol during the
treatment period and for at least 120 days after the last dose of trial
treatment.
9. Male participants must agree to use a contraception as detailed in protocol during the
treatment period and for at least 120 days after the last dose of trial treatment and
refrain from donating sperm during this period.
Exclusion Criteria:
1. Is currently participating and receiving trial therapy or has participated in a trial
of an investigational agent and received trial therapy or used an investigational
device within 4 weeks of the first dose of trial treatment.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment. The use of physiologic doses of corticosteroids may be approved after
consultation with the Sponsor.
3. Has a known history of active TB (Mycobacterium tuberculosis).
4. Hypersensitivity to pembrolizumab or paricalcitol or any of its excipients.
5. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to Cycle
1/Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events
due to agents administered more than 4 weeks earlier.
6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to Cycle1/ Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
baseline) from adverse events due to a previously administered agent(s).
Note: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and may
qualify for the trial.
Note: If patient received major surgery, they must have recovered adequately from the
toxicity and/or complications from the intervention prior to starting therapy.
7. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.
8. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Patients with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging for at least four weeks
prior to the first dose of trial treatment and any neurologic symptoms have returned
to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis, which is excluded regardless of clinical stability.
9. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
10. Has history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
11. Has an active infection requiring systemic therapy.
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the patient's
participation for the full duration of the trial, or is not in the best interest of
the patient to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
15. Has a serum vitamin D level of ≥ 50 ng/mL
16. Currently taking a strong CYP3A inhibitors that cannot be discontinued prior to trial
enrollment and for the duration of trial. This includes but is not is limited to:
boceprevir clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole,
ketoconazole, lopinavir/ritonavir.
17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
18. Has a known history of or is positive for Hepatitis B (e.g., HBsAg reactive) or
Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Note: Without known history testing needs to be performed to determine eligibility.
19. Current, serious, clinically significant cardiac arrhythmias as determined by the
investigator, or patient receiving a digitalis derivative.
20. Has received a live vaccine within 30 days of planned start of trial therapy.
Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated
vaccines, and are not allowed
