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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03331562
Recruitment Status : Completed
First Posted : November 6, 2017
Last Update Posted : October 8, 2020
Sponsor:
Collaborators:
Stand Up To Cancer
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Translational Genomics Research Institute

Tracking Information
First Submitted Date  ICMJE October 18, 2017
First Posted Date  ICMJE November 6, 2017
Last Update Posted Date October 8, 2020
Actual Study Start Date  ICMJE December 27, 2017
Actual Primary Completion Date June 29, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 3, 2017)
Percent of patients with radiographic disease progression according to RECIST 1.1 at 6 months from initiation of trial treatment [ Time Frame: 6 months from trial treatment initiation cycle 1/day 1. Each treatment cycle is 21 days. ]
Difference in progression (by RECIST 1.1) at 6 months between the two treatment arms
Original Primary Outcome Measures  ICMJE
 (submitted: October 31, 2017)
Percent of patients with radiographic disease progression according to RECIST 1.1 at 6 months from initiation of trial treatment [ Time Frame: 6 months from trial treatment initiation cycle 1/day 1 ]
Difference in progression (by RECIST 1.1) at 6 months between the two treatment arms
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 3, 2017)
  • Incidence of treatment-related toxicities as assessed by CTCAE v4.0 from cycle1/day 1 through 30 days after the last dose of trial treatment. [ Time Frame: initiation of trial treatment cycle 1/day 1 through 30 days after last dose of trial treatment. Each treatment cycle is 21 days. ]
    Incidence of toxicities between two treatment arms
  • Difference in overall survival (OS) in patients administered the combination of paricalcitol plus pembrolizumab versus pembrolizumab alone [ Time Frame: From date of treatment initiation cycle 1/day 1 until death from any cause, assessed up to 36 months. ]
    Overall survival between two treatment arms
  • Change in tumor mutational landscape and transcriptional programs using unbiased genome-wide sequencing [ Time Frame: Optional tumor biopsy taken at baseline and at 9 +/- 1 week following initiation of treatment ]
    Mutational landscapes, transcriptional programs in tumor tissue
  • Cellular VDR targets in the immune microenvironment with PD1 blockade [ Time Frame: From baseline, at 9 +/- 1 week following initiation of treatment, at the time of confirmed response, and at the time of trial treatment discontinuation for any reason, up to 24 months ( 35 treatment cycles). ]
    Identify cellular VDR targets in the immune microenvironment
Original Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2017)
  • Incidence of treatment-related toxicities as assessed by CTCAE v4.0 from cycle1/day 1 through 30 days after the last dose of trial treatment. [ Time Frame: initiation of trial treatment cycle 1/day 1 through 30 days after last dose of trial treatment ]
    Incidence of toxicities between two treatment arms
  • Difference in overall survival (OS) in patients administered the combination of paricalcitol plus pembrolizumab versus pembrolizumab alone [ Time Frame: From date of treatment initiation cycle 1/day 1 until death from any cause, assessed up to 36 months. ]
    Overall survival between two treatment arms
  • Change in tumor mutational landscape and transcriptional programs using unbiased genome-wide sequencing [ Time Frame: Optional tumor biopsy taken at baseline and at 9 +/- 1 week following initiation of treatment ]
    Mutational landscapes, transcriptional programs in tumor tissue
  • Cellular VDR targets in the immune microenvironment with PD1 blockade [ Time Frame: From baseline, at 9 +/- 1 week following initiation of treatment, at the time of confirmed response, and at the time of trial treatment discontinuation for any reason, up to 24 months ( 35 treatment cycles). ]
    Identify cellular VDR targets in the immune microenvironment
Current Other Pre-specified Outcome Measures
 (submitted: November 3, 2017)
  • Exploratory: Difference in disease progression according to RECIST 1.1 and iRECIST [ Time Frame: tumor assessments performed every 9 +/- 1 week while on treatment, up to 24 months. ]
    Difference in disease progression according to RECIST 1.1 and iRECIST criteria
  • Exploratory: Utility of a Patient Personalized Clinical Benefit (PPCB) phone based application [ Time Frame: From baseline, patients will complete the PPCB App weekly during trial treatment, and at the time of trial treatment discontinuation for any reason, assessed up to 24 months (35 treatment cycles).Each treatment cycle is 21 days. ]
    Compliance rate responding to a phone - based application for the assessment of patient defined symptoms
  • Exploratory:Improvement in symptoms as recorded by the Patient Personalized Clinical Benefit (PPCB) with progression at 6 months by RECIST 1.1 [ Time Frame: From baseline, patients will complete the PPCB App weekly during trial treatment, and at the time of trial treatment discontinuation for any reason, assessed up to 24 months (35 treatment cycles). Each treatment cycle is 21 days. ]
    Improvement in symptoms as recorded by the Patient Personalized Clinical Benefit (PPCB)
  • Changes in tumor and/or tissue texture on imaging in both arms of the trial using quantitative textural analysis (QTA) [ Time Frame: tumor assessments performed every 9 +/- 1 week while on treatment, up to 24 months. ]
    Differences in tumor and/or tissue texture on CT scans between the two treatment arms
  • Exploratory: Monitor and compare the gut microbial communities in both arms of the trial [ Time Frame: Fecal swab samples collected pre and post dose day 1 of each cycle, up to 35 treatment cycles. Each treatment cycle is 21 days. ]
    Differences in gut microbial communities within and between fecal samples using alpha and beta diversity metrics based on 16S rRNA sequencing
Original Other Pre-specified Outcome Measures
 (submitted: October 31, 2017)
  • Exploratory: Difference in disease progression according to RECIST 1.1 and iRECIST [ Time Frame: tumor assessments performed every 9 +/- 1 week while on treatment, up to 24 months. ]
    Difference in disease progression according to RECIST 1.1 and iRECIST criteria
  • Exploratory: Utility of a Patient Personalized Clinical Benefit (PPCB) phone based application [ Time Frame: From baseline, patients will complete the PPCB App weekly during trial treatment, and at the time of trial treatment discontinuation for any reason, assessed up to 24 months (35 treatment cycles). ]
    Compliance rate responding to a phone - based application for the assessment of patient defined symptoms
  • Exploratory:Improvement in symptoms as recorded by the Patient Personalized Clinical Benefit (PPCB) with progression at 6 months by RECIST 1.1 [ Time Frame: From baseline, patients will complete the PPCB App weekly during trial treatment, and at the time of trial treatment discontinuation for any reason, assessed up to 24 months (35 treatment cycles). ]
    Improvement in symptoms as recorded by the Patient Personalized Clinical Benefit (PPCB)
  • Changes in tumor and/or tissue texture on imaging in both arms of the trial using quantitative textural analysis (QTA) [ Time Frame: tumor assessments performed every 9 +/- 1 week while on treatment, up to 24 months. ]
    Differences in tumor and/or tissue texture on CT scans between the two treatment arms
  • Exploratory: Monitor and compare the gut microbial communities in both arms of the trial [ Time Frame: Fecal swab samples collected pre and post dose day 1 of each cycle, up to 35 treatment cycles ]
    Differences in gut microbial communities within and between fecal samples using alpha and beta diversity metrics based on 16S rRNA sequencing
 
Descriptive Information
Brief Title  ICMJE A SU2C Catalyst® Trial of a PD1 Inhibitor With or Without a Vitamin D Analog for the Maintenance of Pancreatic Cancer
Official Title  ICMJE A SU2C Catalyst ® Randomized Phase II Trial of the PD1 Inhibitor Pembrolizumab With or Without a Vitamin D Receptor Agonist Paricalcitol in Patients With Stage IV Pancreatic Cancer Who Have Been Placed in Best Possible Response
Brief 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.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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
Primary Purpose: Treatment
Condition  ICMJE
  • Pancreatic Cancer
  • Pancreas Adenocarcinoma
  • Advanced Pancreatic Cancer
  • Metastatic Pancreatic Cancer
  • Metastatic Pancreatic Adenocarcinoma
Intervention  ICMJE
  • Drug: Pembrolizumab
    pembrolizumab solution for infusion
    Other Name: Keytruda
  • Drug: paricalcitol
    Paricalcitol solution for injection
    Other Name: Zemplar
  • Drug: placebo
    normal saline solution for injection
    Other Name: placebo for paricalcitol
Study Arms  ICMJE
  • Active Comparator: pembrolizumab & paricalcitol
    pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week
    Interventions:
    • Drug: Pembrolizumab
    • Drug: paricalcitol
  • Placebo Comparator: pembrolizumab & placebo
    pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week
    Interventions:
    • Drug: Pembrolizumab
    • Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 31, 2017)
24
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 10, 2020
Actual Primary Completion Date June 29, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03331562
Other Study ID Numbers  ICMJE TGen 17-001
MISP# 56240 ( Other Identifier: Merck Sharp & Dohme Corp. a Subsidiary of Merck & Co., Inc. )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Translational Genomics Research Institute
Study Sponsor  ICMJE Translational Genomics Research Institute
Collaborators  ICMJE
  • Stand Up To Cancer
  • Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Daniel D Von Hoff, MD, FACS Translational Genomics Research Institute (TGen) An Affiliate of City of Hope
PRS Account Translational Genomics Research Institute
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP