A SU2C Catalyst® Trial of a PD1 Inhibitor With or Without a Vitamin D Analog for the Maintenance of Pancreatic Cancer

• Status: Completed
• Trial end date: 2020-07-10
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Translational Genomics Research Institute
• Collaborators: Merck Sharp & Dohme Corp.; Stand Up To Cancer
• Treatments: Ergocalciferols; Pembrolizumab; Retinol palmitate; Vitamin A; Vitamin D; Vitamins

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 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