A SU2C Catalyst® Trial of a PD1 Inhibitor With or Without a Vitamin D Analog for the Maintenance of Pancreatic Cancer
Condition: Pancreatic Cancer; Pancreas Adenocarcinoma; Advanced Pancreatic Cancer; Metastatic Pancreatic Cancer; Metastatic Pancreatic Adenocarcinoma
MeSH terms: Adenocarcinoma; Pancreatic Neoplasms
Intervention: Pembrolizumab; paricalcitol; placebo
Intervention description: pembrolizumab solution for infusion; Paricalcitol solution for injection; normal saline solution for injection
Intervention MeSH terms: Ergocalciferols; Pembrolizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This is a double-blind, randomized, placebo-controlled phase II trial with the identity of the treatment unknown to the patients, investigators, and the Sponsor.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Placebo controlled
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pembrolizumab; Paricalcitol; Pancreatic cancer; Metastatic Pancreatic Cancer; Vitamin D Receptor (VDR); Immune Checkpoint Inhibitor; VDR agonist; PD1 Inhibitor

Summary:

      Chemotherapy regimens for pancreatic cancer can now stabilize a patient's cancer and/or place
      some patients in remission or partial remission. The challenge now is to find options for
      maintenance therapies that will improve survival and allow continued benefits with minimal
      toxicities and inconvenience to the patients. This study will determine the effects of one
      possible maintenance regimen.

      The study is being conducted to determine the effects that pembrolizumab with or without the
      addition of paricalcitol may have on pancreatic cancer. Half of the patients will be
      randomized to receive pembrolizumab + paricalcitol and half to receive pembrolizumab +
      placebo.
    

Eligibility criteria:

        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 Eastern Cooperative Oncology Group (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 Upper Limit of Normal (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 cytochrome P450 3A (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 virus (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