Study NCT03331562
A SU2C Catalyst® Trial of a PD1 Inhibitor With or Without a Vitamin D Analog for the Maintenance of Pancreatic Cancer
Submitted Date:  November 9, 2021 (v11)
Quality Control Review Has Not Concluded

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This submission includes brief standardized QC review comments added by the National Library of Medicine (NLM). These comments indicate the location of apparent errors, deficiencies, or inconsistencies. For more information, see the Final Rule (42 CFR Part 11) Information page.


Open or close this module Study Identification
Unique Protocol ID: TGen 17-001
Brief Title: A SU2C Catalyst® Trial of a PD1 Inhibitor With or Without a Vitamin D Analog for the Maintenance of Pancreatic Cancer
Official Title: 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
Secondary IDs: MISP# 56240 [Merck Sharp & Dohme Corp. a Subsidiary of Merck & Co., Inc.]
Open or close this module Study Status
Record Verification: November 2021
Overall Status: Completed
Study Start: December 27, 2017
Primary Completion: June 29, 2020 [Actual]
Study Completion: July 10, 2020 [Actual]
First Submitted: October 18, 2017
First Submitted that
Met QC Criteria:
October 31, 2017
First Posted: November 6, 2017 [Actual]
Results First Submitted: November 9, 2021
Results First Submitted that
Met QC Criteria:
Results First Posted: December 8, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
Last Update Posted: December 8, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Translational Genomics Research Institute
Responsible Party: Sponsor
Collaborators: Stand Up To Cancer
Merck Sharp & Dohme LLC
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.

Open or close this module Conditions
Conditions: Pancreatic Cancer
Pancreas Adenocarcinoma
Advanced Pancreatic Cancer
Metastatic Pancreatic Cancer
Metastatic Pancreatic Adenocarcinoma
Keywords: Pembrolizumab
Paricalcitol
Pancreatic cancer
Metastatic Pancreatic Cancer
Vitamin D Receptor (VDR)
Immune Checkpoint Inhibitor
VDR agonist
PD1 Inhibitor
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
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.
Number of Arms: 2
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 24 [Actual]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: pembrolizumab & paricalcitol
pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week
Drug: Pembrolizumab
pembrolizumab solution for infusion
Other Names:
  • Keytruda
Drug: paricalcitol
Paricalcitol solution for injection
Other Names:
  • Zemplar
Placebo Comparator: pembrolizumab & placebo
pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week
Drug: Pembrolizumab
pembrolizumab solution for infusion
Other Names:
  • Keytruda
Drug: placebo
normal saline solution for injection
Other Names:
  • placebo for paricalcitol
Open or close this module Outcome Measures
[See Results Section.]
Primary Outcome Measures:
1. Progression- Free Survival 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. ]

Progression- free survival (by RECIST 1.1) at 6 months
Secondary Outcome Measures:
1. 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
2. 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

Quality Control Review Comment provided by the National Library of Medicine:

  1. The Time Frame appears inconsistent with information provided here or in other parts of the record.
3. 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
4. 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
Other Outcome Measures:
1. 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
2. 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 = number of completed assessments/number of expected assessments
3. 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)
4. 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
5. 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
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
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

Open or close this module Contacts/Locations
Study Officials: Daniel D Von Hoff, MD, FACS
Study Director
Translational Genomics Research Institute (TGen) An Affiliate of City of Hope
Locations: United States, Arizona
HonorHealth Research Institute
Scottsdale, Arizona, United States, 85258
United States, California
City of Hope National Medical Center
Duarte, California, United States, 91010
United States, Kansas
The University of Kansas Cancer Center
Westwood, Kansas, United States, 66205
United States, New Jersey
Atlantic Medical Group-Oncology Morristown Medical Center
Morristown, New Jersey, United States, 07962
United States, Texas
Baylor University Medical Center Charles A. Sammons Cancer Center
Dallas, Texas, United States, 75246
United States, Wisconsin
Froedtert Hospital and Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:
Open or close this module Document Section
Study Protocol
Document Date: August 29, 2019
Uploaded: 11/09/2021 10:46
File Name: Prot_000.pdf
Statistical Analysis Plan
Document Date: July 10, 2020
Uploaded: 11/09/2021 10:47
File Name: SAP_001.pdf
Study Results
Open or close this module Participant Flow
Recruitment Details
Pre-assignment Details
 
Arm/Group Title Pembrolizumab & Paricalcitol Pembrolizumab & Placebo
Arm/Group Description

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

Period Title: Overall Study
Started [1] 12 12
Completed [2] 9 12
Not Completed 3 0
Reason Not Completed
Adverse Event 2 0
Death 1 0
[1]Randomized to study arm, received allocated study treatment
[2]Patients continued on study treatment until disease progression
Open or close this module Baseline Characteristics
Arm/Group TitlePembrolizumab & ParicalcitolPembrolizumab & PlaceboTotal
Arm/Group Description

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

Total of all reporting groups
Overall Number of Baseline Participants 12 12 24
Baseline Analysis Population Description [Not Specified]
Age, Continuous
Median (Full Range)
Unit of measure: years
Number Analyzed12 Participants12 Participants24 Participants
63.8(42.9 to 77.9)69.3(50.5 to 76.7)67.6(42.9 to 77.9)
Sex: Female, Male
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed12 Participants12 Participants24 Participants
Female
6
50%
7
58.33%
13
54.17%
Male
6
50%
5
41.67%
11
45.83%
Ethnicity (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed12 Participants12 Participants24 Participants
Hispanic or Latino
1
8.33%
1
8.33%
2
8.33%
Not Hispanic or Latino
11
91.67%
11
91.67%
22
91.67%
Unknown or Not Reported
0
0%
0
0%
0
0%
Race (NIH/OMB)
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed12 Participants12 Participants24 Participants
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
1
8.33%
0
0%
1
4.17%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
1
8.33%
1
8.33%
2
8.33%
White
10
83.33%
11
91.67%
21
87.5%
More than one race
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
Region of Enrollment
Measure Type: Number
Unit of measure: participants
Number Analyzed12 Participants12 Participants24 Participants
United States
121224
ECOG Performance Status
Measure Type: Count of Participants
Unit of measure: Participants
Number Analyzed12 Participants12 Participants24 Participants
ECOG 0
5
41.67%
4
33.33%
9
37.5%
ECOG 1
7
58.33%
8
66.67%
15
62.5%

Quality Control Review Comment provided by the National Library of Medicine:

  1. The description of the scale or categories does not include sufficient information to understand the results reported.
Open or close this module Outcome Measures
1. Primary Outcome:
Title Progression- Free Survival at 6 Months From Initiation of Trial Treatment
Description Progression- free survival (by RECIST 1.1) at 6 months
Time Frame 6 months from trial treatment initiation cycle 1/day 1. Each treatment cycle is 21 days.
Outcome Measure Data
Analysis Population Description
All patients that receive trial treatment will be included in the analysis. Excludes 3 participants in the pembrolizumab + paricalcitol group: 1 participant that died due to other cause before 6 months, 2 participants who withdrew from study treatment before 6 months.
 
Arm/Group TitlePembrolizumab & ParicalcitolPembrolizumab & Placebo
Arm/Group Description

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

Overall Number of Participants Analyzed9 12
Measure Type: Count of Participants
Unit of Measure: Participants
0
0%
2
16.7%
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionPembrolizumab & Placebo
Comments[Not specified]
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value.31
Comments[Not specified]
MethodFisher Exact
Comments[Not specified]
Method of EstimationEstimation ParameterRisk Ratio (RR)
Estimated Value0
Confidence Interval(1-Sided) 95%
0
Estimation CommentsLower bound cannot be estimated because there were 0 events in the comparison group.
2. Secondary Outcome:
Title 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.
Description Incidence of toxicities between two treatment arms
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.
Outcome Measure Data
Analysis Population Description
All patients who received any amount of trial treatment were included in the analysis. The reported AEs are those noted as possibly or definitely related to study agents.
 
Arm/Group TitlePembrolizumab & ParicalcitolPembrolizumab & Placebo
Arm/Group Description

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

Overall Number of Participants Analyzed12 12
Measure Type: Count of Participants
Unit of Measure: Participants
Abdominal bloating
1
8.3%
0
0%
Abdominal pain
1
8.3%
2
16.7%
ALT increase
2
16.7%
0
0%
Alkaline phosphatase increase
1
8.3%
0
0%
Anemia
0
0%
1
8.3%
Arthralgia
2
16.7%
0
0%
AST increase
2
16.7%
1
8.3%
Creatinine increase
2
16.7%
0
0%
Hypertension
0
0%
2
16.7%
Hypophysitis
1
8.3%
0
0%
Nausea
1
8.3%
0
0%
Pruritis
1
8.3%
0
0%
Uticaria
0
0%
1
8.3%
Vomiting
1
8.3%
0
0%
3. Secondary Outcome:
Title Difference in Overall Survival (OS) in Patients Administered the Combination of Paricalcitol Plus Pembrolizumab Versus Pembrolizumab Alone
Description Overall survival between two treatment arms
Time Frame From date of treatment initiation cycle 1/day 1 until death from any cause, assessed up to 36 months.

Quality Control Review Comment provided by the National Library of Medicine:

  1. The Time Frame appears inconsistent with information provided here or in other parts of the record.
Outcome Measure Data
Analysis Population Description
Number of participants alive at 6 months
 
Arm/Group TitlePembrolizumab & ParicalcitolPembrolizumab & Placebo
Arm/Group Description

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

Overall Number of Participants Analyzed12 12
Measure Type: Count of Participants
Unit of Measure: Participants
8
66.7%
9
75%
Statistical Analysis 1
Statistical Analysis OverviewComparison Group SelectionPembrolizumab & Placebo
Comments[Not specified]
Type of Statistical TestSuperiority
Comments[Not specified]
Statistical Test of HypothesisP-Value.47
Comments[Not specified]
MethodRegression, Cox
Comments[Not specified]
Method of EstimationEstimation ParameterHazard Ratio (HR)
Estimated Value1.56
Confidence Interval(2-sided) 95%
.46 to 5.29
Estimation Comments[Not specified]
4. Secondary Outcome:
Title Change in Tumor Mutational Landscape and Transcriptional Programs Using Unbiased Genome-wide Sequencing
Description Mutational landscapes, transcriptional programs in tumor tissue
Time Frame Optional tumor biopsy taken at baseline and at 9 +/- 1 week following initiation of treatment
Outcome Measure Data
Analysis Population Description
Data could not be analyzed due to lack of funding for the project.
 
Arm/Group TitlePembrolizumab & ParicalcitolPembrolizumab & Placebo
Arm/Group Description

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

Overall Number of Participants Analyzed0 0
No data displayed because Outcome Measure has zero total participants analyzed.
5. Secondary Outcome:
Title Cellular VDR Targets in the Immune Microenvironment With PD1 Blockade
Description Identify cellular VDR targets in the immune microenvironment
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).
Outcome Measure Data
Analysis Population Description
Due to lack of funding, this analysis could not be performed.
 
Arm/Group TitlePembrolizumab & ParicalcitolPembrolizumab & Placebo
Arm/Group Description

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

Overall Number of Participants Analyzed0 0
No data displayed because Outcome Measure has zero total participants analyzed.
6. Other Pre-specified Outcome:
Title Exploratory: Difference in Disease Progression According to RECIST 1.1 and iRECIST
Description Difference in disease progression according to RECIST 1.1 and iRECIST criteria
Time Frame tumor assessments performed every 9 +/- 1 week while on treatment, up to 24 months.
Outcome Measure Data
Analysis Population Description
This planned analysis was not performed, as we were not able to obtain confirmation of disease progression by iRECIST for a majority of the patients.
 
Arm/Group TitlePembrolizumab & ParicalcitolPembrolizumab & Placebo
Arm/Group Description

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

Overall Number of Participants Analyzed0 0
No data displayed because Outcome Measure has zero total participants analyzed.
7. Other Pre-specified Outcome:
Title Exploratory: Utility of a Patient Personalized Clinical Benefit (PPCB) Phone Based Application
Description Compliance rate = number of completed assessments/number of expected assessments
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.
Outcome Measure Data
Analysis Population Description
All patients completed the weekly questionnaire and were included in the analysis.
 
Arm/Group TitleAll Participants
Arm/Group DescriptionCompliance rate for all participants treated across both arms
Overall Number of Participants Analyzed24
Measure Type: Number
Unit of Measure: % of expected questionnaires completed
89.1

Quality Control Review Comment provided by the National Library of Medicine:

  1. The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided.
8. Other Pre-specified Outcome:
Title Exploratory:Improvement in Symptoms as Recorded by the Patient Personalized Clinical Benefit (PPCB) With Progression at 6 Months by RECIST 1.1
Description Improvement in symptoms as recorded by the Patient Personalized Clinical Benefit (PPCB)
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.
Outcome Measure Data
Analysis Population Description
All participants across both arms
 
Arm/Group TitleAll Participants
Arm/Group DescriptionAll participants that completed the questionnaires
Overall Number of Participants Analyzed24
Measure Type: Count of Participants
Unit of Measure: Participants
Improvement in symptoms
15
62.5%
Worsening in symptoms
7
29.2%
No change in symptoms
2
8.3%

Quality Control Review Comment provided by the National Library of Medicine:

  1. The arms/groups appear inconsistent with information in other parts of the record. Each arm/group should be described separately, or a valid explanation provided.
9. Other Pre-specified Outcome:
Title Changes in Tumor and/or Tissue Texture on Imaging in Both Arms of the Trial Using Quantitative Textural Analysis (QTA)
Description Differences in tumor and/or tissue texture on CT scans between the two treatment arms
Time Frame tumor assessments performed every 9 +/- 1 week while on treatment, up to 24 months.
Outcome Measure Data
Analysis Population Description
Due to lack of funding analysis could be be completed.
 
Arm/Group TitlePembrolizumab & ParicalcitolPembrolizumab & Placebo
Arm/Group Description

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

Overall Number of Participants Analyzed0 0
No data displayed because Outcome Measure has zero total participants analyzed.
10. Other Pre-specified Outcome:
Title Exploratory: Monitor and Compare the Gut Microbial Communities in Both Arms of the Trial
Description Differences in gut microbial communities within and between fecal samples using alpha and beta diversity metrics based on 16S rRNA sequencing
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.
Outcome Measure Data
Analysis Population Description
Due to lack of funding analysis could be be completed.
 
Arm/Group TitlePembrolizumab & ParicalcitolPembrolizumab & Placebo
Arm/Group Description

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

Overall Number of Participants Analyzed0 0
No data displayed because Outcome Measure has zero total participants analyzed.
Open or close this module Adverse Events
 
Time Frame Adverse events were collected from the time of treatment allocation/randomization through 30 days following cessation of study treatment.
Adverse Event Reporting Description Participants with multiple events for a given AE term were counted only once for each AE term. If the same AE term was reported more than once for a participant, only the AE term with the highest grade was included.
 
Arm/Group Title Pembrolizumab & Paricalcitol Pembrolizumab & Placebo
Arm/Group Description

pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

paricalcitol: Paricalcitol solution for injection

pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week

Pembrolizumab: pembrolizumab solution for infusion

placebo: normal saline solution for injection

All-Cause Mortality
  Pembrolizumab & ParicalcitolPembrolizumab & Placebo
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 8 / 12 (66.67%)4 / 12 (33.33%)
Serious Adverse Events
  Pembrolizumab & ParicalcitolPembrolizumab & Placebo
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 4 / 12 (33.33%)4 / 12 (33.33%)
Cardiac disorders
Cardiac disorders - Other, takotsubo cardiomyopathy † A 1 / 12 (8.33%)10 / 12 (0%)0
Myocardial infarction † A 1 / 12 (8.33%)10 / 12 (0%)0
Gastrointestinal disorders
Abdominal pain † A 1 / 12 (8.33%)11 / 12 (8.33%)1
Obstruction gastric † A 1 / 12 (8.33%)10 / 12 (0%)0
Vomiting † A 1 / 12 (8.33%)10 / 12 (0%)0
Infections and infestations
Abdominal infection † A 1 / 12 (8.33%)10 / 12 (0%)0
Sepsis † A 1 / 12 (8.33%)10 / 12 (0%)0
Investigations
Blood bilirubin increased † A 0 / 12 (0%)01 / 12 (8.33%)1
Lipase increased † A 1 / 12 (8.33%)10 / 12 (0%)0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Neoplasms- Squamous Cell Carcinoma † A 0 / 12 (0%)02 / 12 (16.67%)2
Nervous system disorders
Stroke † A 1 / 12 (8.33%)10 / 12 (0%)0
Psychiatric disorders
Confusion † A 1 / 12 (8.33%)10 / 12 (0%)0
Renal and urinary disorders
Renal and urinary disorders - Other, hepatorenal syndrome † A 1 / 12 (8.33%)10 / 12 (0%)0
Respiratory, thoracic and mediastinal disorders
Pleural effusion † A 1 / 12 (8.33%)10 / 12 (0%)0
Indicates events were collected by systematic assessment.
ATerm from vocabulary, NCI CTCAE Version 4
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
  Pembrolizumab & ParicalcitolPembrolizumab & Placebo
 Affected / At Risk (%)# Events Affected / At Risk (%)# Events
Total 12 / 12 (100%)12 / 12 (100%)
Blood and lymphatic system disorders
Anemia † A 5 / 12 (41.67%)53 / 12 (25%)3
Cardiac disorders
Atrial fibrillation † A 1 / 12 (8.33%)10 / 12 (0%)0
Cardiac disorders - other, cardiomegaly † A 1 / 12 (8.33%)10 / 12 (0%)0
Chest pain - cardiac † A 0 / 12 (0%)01 / 12 (8.33%)1
Heart failure † A 1 / 12 (8.33%)10 / 12 (0%)0
Sinus bradycardia † A 0 / 12 (0%)01 / 12 (8.33%)1
Endocrine disorders
Endocrine disorders - other, hypophysitis † A 1 / 12 (8.33%)10 / 12 (0%)0
Eye disorders
Blurred vision † A 0 / 12 (0%)01 / 12 (8.33%)1
Cataract † A 0 / 12 (0%)02 / 12 (16.67%)2
Dry eye † A 1 / 12 (8.33%)10 / 12 (0%)0
Photophobia † A 0 / 12 (0%)01 / 12 (8.33%)1
Gastrointestinal disorders
Abdominal distension † A 1 / 12 (8.33%)10 / 12 (0%)0
Abdominal pain † A 2 / 12 (16.67%)23 / 12 (25%)3
Bloating † A 3 / 12 (25%)30 / 12 (0%)0
Constipation † A 3 / 12 (25%)30 / 12 (0%)0
Dental caries † A 0 / 12 (0%)01 / 12 (8.33%)1
Diarrhea † A 2 / 12 (16.67%)22 / 12 (16.67%)2
Dyspepsia † A 1 / 12 (8.33%)10 / 12 (0%)0
Flatulence † A 1 / 12 (8.33%)10 / 12 (0%)0
Gastroesophageal reflux disease † A 2 / 12 (16.67%)20 / 12 (0%)0
Gastrointestinal disorder other: bleeding with stools † A 1 / 12 (8.33%)10 / 12 (0%)0
Gastrointestinal disorders - cramping † A 1 / 12 (8.33%)10 / 12 (0%)0
Nausea † A 5 / 12 (41.67%)53 / 12 (25%)3
Small intestinal obstruction † A 1 / 12 (8.33%)10 / 12 (0%)0
Vomiting † A 1 / 12 (8.33%)12 / 12 (16.67%)2
hemorrhoids † A 1 / 12 (8.33%)10 / 12 (0%)0
General disorders
Chills † A 1 / 12 (8.33%)10 / 12 (0%)0
Edema limbs † A 1 / 12 (8.33%)11 / 12 (8.33%)1
Fatigue † A 2 / 12 (16.67%)21 / 12 (8.33%)1
Fever † A 1 / 12 (8.33%)12 / 12 (16.67%)2
Flu-like symptoms † A 0 / 12 (0%)01 / 12 (8.33%)1
Gait disturbance † A 2 / 12 (16.67%)20 / 12 (0%)0
Non-cardiac chest pain † A 1 / 12 (8.33%)10 / 12 (0%)0
Other- cold sensitivity † A 1 / 12 (8.33%)10 / 12 (0%)0
Hepatobiliary disorders
Hepatobiliary disorders other: biliary obstruction † A 1 / 12 (8.33%)10 / 12 (0%)0
Infections and infestations
Kidney infection † A 1 / 12 (8.33%)10 / 12 (0%)0
Papulopustular rash † A 0 / 12 (0%)01 / 12 (8.33%)1
Upper respiratory infection † A 0 / 12 (0%)01 / 12 (8.33%)1
Urinary tract infection † A 0 / 12 (0%)02 / 12 (16.67%)2
Injury, poisoning and procedural complications
Intestinal stoma obstruction † A 1 / 12 (8.33%)10 / 12 (0%)0
Investigations
Activated partial thromboplastin time prolonged † A 1 / 12 (8.33%)10 / 12 (0%)0
Alanine aminotransferase increased † A 3 / 12 (25%)33 / 12 (25%)3
Alkaline phosphatase increased † A 3 / 12 (25%)31 / 12 (8.33%)1
Aspartate aminotransferase increased † A 4 / 12 (33.33%)43 / 12 (25%)3
Blood bilirubin increased † A 1 / 12 (8.33%)10 / 12 (0%)0
Creatinine increased † A 2 / 12 (16.67%)20 / 12 (0%)0
Other, lactic acid increased † A 1 / 12 (8.33%)10 / 12 (0%)0
Other, neutrophil count increased † A 1 / 12 (8.33%)10 / 12 (0%)0
Other, thyroid stimulating hormone increased † A 1 / 12 (8.33%)10 / 12 (0%)0
Other- ammonia increased † A 1 / 12 (8.33%)10 / 12 (0%)0
Platelet count decreased † A 0 / 12 (0%)01 / 12 (8.33%)1
Weight loss † A 1 / 12 (8.33%)10 / 12 (0%)0
White blood cell decreased † A 1 / 12 (8.33%)10 / 12 (0%)0
Metabolism and nutrition disorders
Alkalosis † A 1 / 12 (8.33%)10 / 12 (0%)0
Anorexia † A 2 / 12 (16.67%)20 / 12 (0%)0
Hypercalcemia † A 2 / 12 (16.67%)20 / 12 (0%)0
Hyperglycemia † A 0 / 12 (0%)01 / 12 (8.33%)1
Hypokalemia † A 1 / 12 (8.33%)10 / 12 (0%)0
Hypomagnesemia † A 1 / 12 (8.33%)10 / 12 (0%)0
Hyponatremia † A 1 / 12 (8.33%)11 / 12 (8.33%)1
Musculoskeletal and connective tissue disorders
Arthralgia † A 2 / 12 (16.67%)22 / 12 (16.67%)2
Back pain † A 1 / 12 (8.33%)13 / 12 (25%)3
Generalized muscle weakness † A 1 / 12 (8.33%)10 / 12 (0%)0
Other, temporomandibular joint pain † A 0 / 12 (0%)01 / 12 (8.33%)1
Pain † A 1 / 12 (8.33%)10 / 12 (0%)0
Pain in extremity † A 1 / 12 (8.33%)12 / 12 (16.67%)2
Nervous system disorders
Dizziness † A 1 / 12 (8.33%)10 / 12 (0%)0
Headache † A 1 / 12 (8.33%)11 / 12 (8.33%)1
Syncope † A 0 / 12 (0%)01 / 12 (8.33%)1
Transient ischemic attacks † A 1 / 12 (8.33%)10 / 12 (0%)0
Psychiatric disorders
Agitation † A 1 / 12 (8.33%)10 / 12 (0%)0
Anxiety † A 1 / 12 (8.33%)10 / 12 (0%)0
Depression † A 1 / 12 (8.33%)10 / 12 (0%)0
Renal and urinary disorders
Acute kidney injury † A 1 / 12 (8.33%)10 / 12 (0%)0
Hematuria † A 0 / 12 (0%)01 / 12 (8.33%)1
Proteinuria † A 1 / 12 (8.33%)10 / 12 (0%)0
Urinary frequency † A 0 / 12 (0%)01 / 12 (8.33%)1
Respiratory, thoracic and mediastinal disorders
Aspiration † A 1 / 12 (8.33%)10 / 12 (0%)0
Cough † A 2 / 12 (16.67%)20 / 12 (0%)0
Dyspnea † A 1 / 12 (8.33%)11 / 12 (8.33%)1
Nasal congestion † A 0 / 12 (0%)01 / 12 (8.33%)1
Pulmonary edema † A 1 / 12 (8.33%)10 / 12 (0%)0
Sore throat † A 1 / 12 (8.33%)10 / 12 (0%)0
Skin and subcutaneous tissue disorders
Alopecia † A 0 / 12 (0%)01 / 12 (8.33%)1
Nail discoloration † A 0 / 12 (0%)01 / 12 (8.33%)1
Pruritis † A 1 / 12 (8.33%)10 / 12 (0%)0
Uticaria † A 0 / 12 (0%)01 / 12 (8.33%)1
Vascular disorders
Hot flash † A 1 / 12 (8.33%)10 / 12 (0%)0
Hypertension † A 2 / 12 (16.67%)23 / 12 (25%)3
Hypotension † A 2 / 12 (16.67%)20 / 12 (0%)0
Indicates events were collected by systematic assessment.
ATerm from vocabulary, NCI CTCAE Version 4
Open or close this module Limitations and Caveats
Due to lack of grant funding, the other exploratory objectives to assess the changes in tumor and/or tissue texture on imaging, and to monitor and compare gut microbial communities in both arms, have not yet been able to be accomplished. The Investigators are looking for some way to fund the exploratory objectives in the future.
Open or close this module More Information
Certain Agreements:
Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact:
Name/Official Title:
Derek Cridebring, PhD. Director, Molecular Medicine Division
Organization:
Translational Genomics Research Institute (TGen) An Affiliate of City of Hope
Phone:
6023438629
Email:
dcridebring@tgen.org

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