Advanced Pancreatic Cancer, Metastatic Pancreatic Adenocarcinoma, Metastatic Pancreatic Cancer, Pancreas Adenocarcinoma, Pancreatic Cancer
Conditions
Keywords
Pembrolizumab, Paricalcitol, Pancreatic cancer, Metastatic Pancreatic Cancer, Vitamin D Receptor (VDR), Immune Checkpoint Inhibitor, VDR agonist, PD1 Inhibitor
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.
Interventions
DRUGPembrolizumab
pembrolizumab solution for infusion
DRUGparicalcitol
Paricalcitol solution for injection
DRUGplacebo
normal saline solution for injection
Sponsors
Stand Up To Cancer
Merck Sharp & Dohme LLC
Translational Genomics Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Placebo controlled
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression- Free Survival at 6 Months From Initiation of Trial Treatment | 6 months from trial treatment initiation cycle 1/day 1. Each treatment cycle is 21 days. | Progression Free Survival (PFS) defined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) survival in the absence of death or progressive disease which is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | initiation of trial treatment cycle 1/day 1 through 30 days after last dose of trial treatment. Each treatment cycle is 21 days. | All adverse events occurring on or after Cycle 1/day 1through 30 days after the last dose of trial treatment will be summarized by body systems and per grade according to NCI-CTCAE Version 4. |
| Difference in Overall Survival (OS) in Patients Administered the Combination of Paricalcitol Plus Pembrolizumab Versus Pembrolizumab Alone | From date of treatment initiation cycle 1/day 1 until death from any cause, assessed up to 24 months ( the end of the study). | Duration of survival will be defined as the time from initial treatment (cycle1/day1) until death. Overall survival will be estimated for each arm using a Kaplan-Meier estimate. |
| Change in Tumor Mutational Landscape and Transcriptional Programs Using Unbiased Genome-wide Sequencing | 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 | 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
| Measure | Time frame | Description |
|---|---|---|
| Exploratory: Difference in Disease Progression According to RECIST 1.1 and iRECIST | 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 | 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. | Patient compliance rate of completing the PPCB application was calculated by the total percentage of completed questionnaires over expected questionnaires across all participants. |
| Exploratory:Improvement in Symptoms as Recorded by the Patient Personalized Clinical Benefit (PPCB) With Progression at 6 Months by RECIST 1.1 | 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) | 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 | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab & Paricalcitol 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 | 12 |
| Pembrolizumab & Placebo 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 | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Death | 1 | 0 |
Baseline characteristics
| Characteristic | Pembrolizumab & Paricalcitol | Pembrolizumab & Placebo | Total |
|---|---|---|---|
| Age, Continuous | 63.8 years | 69.3 years | 67.6 years |
| ECOG Performance Status ECOG 0 | 5 Participants | 4 Participants | 9 Participants |
| ECOG Performance Status ECOG 1 | 7 Participants | 8 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 11 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 11 Participants | 21 Participants |
| Region of Enrollment United States | 12 participants | 12 participants | 24 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 12 | 4 / 12 |
| other Total, other adverse events | 12 / 12 | 12 / 12 |
| serious Total, serious adverse events | 4 / 12 | 4 / 12 |
Outcome results
Primary
Progression- Free Survival at 6 Months From Initiation of Trial Treatment
Progression Free Survival (PFS) defined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) survival in the absence of death or progressive disease which is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).
Time frame: 6 months from trial treatment initiation cycle 1/day 1. Each treatment cycle is 21 days.
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab & Paricalcitol | Progression- Free Survival at 6 Months From Initiation of Trial Treatment | 0 Participants |
| Pembrolizumab & Placebo | Progression- Free Survival at 6 Months From Initiation of Trial Treatment | 2 Participants |
p-value: 0.31Fisher Exact
Secondary
Cellular VDR Targets in the Immune Microenvironment With PD1 Blockade
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).
Population: Due to lack of funding, this analysis could not be performed.
Secondary
Change in Tumor Mutational Landscape and Transcriptional Programs Using Unbiased Genome-wide Sequencing
Mutational landscapes, transcriptional programs in tumor tissue
Time frame: Optional tumor biopsy taken at baseline and at 9 +/- 1 week following initiation of treatment
Population: Data could not be analyzed due to lack of funding for the project.
Secondary
Difference in Overall Survival (OS) in Patients Administered the Combination of Paricalcitol Plus Pembrolizumab Versus Pembrolizumab Alone
Duration of survival will be defined as the time from initial treatment (cycle1/day1) until death. Overall survival will be estimated for each arm using a Kaplan-Meier estimate.
Time frame: From date of treatment initiation cycle 1/day 1 until death from any cause, assessed up to 24 months ( the end of the study).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab & Paricalcitol | Difference in Overall Survival (OS) in Patients Administered the Combination of Paricalcitol Plus Pembrolizumab Versus Pembrolizumab Alone | 10.4 months |
| Pembrolizumab & Placebo | Difference in Overall Survival (OS) in Patients Administered the Combination of Paricalcitol Plus Pembrolizumab Versus Pembrolizumab Alone | NA months |
Secondary
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.
All adverse events occurring on or after Cycle 1/day 1through 30 days after the last dose of trial treatment will be summarized by body systems and per grade according to NCI-CTCAE Version 4.
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.
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pembrolizumab & Paricalcitol | 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. | ALT increase | 2 Participants |
| Pembrolizumab & Paricalcitol | 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. | AST increase | 2 Participants |
| Pembrolizumab & Paricalcitol | 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. | Vomiting | 1 Participants |
| Pembrolizumab & Paricalcitol | 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. | Creatinine increase | 2 Participants |
| Pembrolizumab & Paricalcitol | 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. | Alkaline phosphatase increase | 1 Participants |
| Pembrolizumab & Paricalcitol | 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. | Hypertension | 0 Participants |
| Pembrolizumab & Paricalcitol | 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. | Abdominal pain | 1 Participants |
| Pembrolizumab & Paricalcitol | 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. | Hypophysitis | 1 Participants |
| Pembrolizumab & Paricalcitol | 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. | Anemia | 0 Participants |
| Pembrolizumab & Paricalcitol | 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. | Nausea | 1 Participants |
| Pembrolizumab & Paricalcitol | 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. | Abdominal bloating | 1 Participants |
| Pembrolizumab & Paricalcitol | 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. | Pruritis | 1 Participants |
| Pembrolizumab & Paricalcitol | 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. | Arthralgia | 2 Participants |
| Pembrolizumab & Paricalcitol | 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. | Uticaria | 0 Participants |
| Pembrolizumab & Placebo | 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. | Uticaria | 1 Participants |
| Pembrolizumab & Placebo | 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. | Vomiting | 0 Participants |
| Pembrolizumab & Placebo | 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. | Abdominal bloating | 0 Participants |
| Pembrolizumab & Placebo | 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. | Abdominal pain | 2 Participants |
| Pembrolizumab & Placebo | 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. | ALT increase | 0 Participants |
| Pembrolizumab & Placebo | 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. | Alkaline phosphatase increase | 0 Participants |
| Pembrolizumab & Placebo | 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. | Anemia | 1 Participants |
| Pembrolizumab & Placebo | 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. | Arthralgia | 0 Participants |
| Pembrolizumab & Placebo | 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. | AST increase | 1 Participants |
| Pembrolizumab & Placebo | 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. | Creatinine increase | 0 Participants |
| Pembrolizumab & Placebo | 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. | Hypertension | 2 Participants |
| Pembrolizumab & Placebo | 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. | Hypophysitis | 0 Participants |
| Pembrolizumab & Placebo | 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. | Nausea | 0 Participants |
| Pembrolizumab & Placebo | 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. | Pruritis | 0 Participants |
Other Pre-specified
Changes in Tumor and/or Tissue Texture on Imaging in Both Arms of the Trial Using Quantitative Textural Analysis (QTA)
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.
Population: Due to lack of funding analysis could be be completed.
Other Pre-specified
Exploratory: Difference in Disease Progression According to RECIST 1.1 and iRECIST
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.
Population: 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.
Other Pre-specified
Exploratory:Improvement in Symptoms as Recorded by the Patient Personalized Clinical Benefit (PPCB) With Progression at 6 Months by RECIST 1.1
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pembrolizumab & Paricalcitol | Exploratory:Improvement in Symptoms as Recorded by the Patient Personalized Clinical Benefit (PPCB) With Progression at 6 Months by RECIST 1.1 | Improvement in symptoms | 8 Participants |
| Pembrolizumab & Paricalcitol | Exploratory:Improvement in Symptoms as Recorded by the Patient Personalized Clinical Benefit (PPCB) With Progression at 6 Months by RECIST 1.1 | Worsening in symptoms | 4 Participants |
| Pembrolizumab & Paricalcitol | Exploratory:Improvement in Symptoms as Recorded by the Patient Personalized Clinical Benefit (PPCB) With Progression at 6 Months by RECIST 1.1 | No change in symptoms | 0 Participants |
| Pembrolizumab & Placebo | Exploratory:Improvement in Symptoms as Recorded by the Patient Personalized Clinical Benefit (PPCB) With Progression at 6 Months by RECIST 1.1 | Improvement in symptoms | 7 Participants |
| Pembrolizumab & Placebo | Exploratory:Improvement in Symptoms as Recorded by the Patient Personalized Clinical Benefit (PPCB) With Progression at 6 Months by RECIST 1.1 | Worsening in symptoms | 3 Participants |
| Pembrolizumab & Placebo | Exploratory:Improvement in Symptoms as Recorded by the Patient Personalized Clinical Benefit (PPCB) With Progression at 6 Months by RECIST 1.1 | No change in symptoms | 2 Participants |
Other Pre-specified
Exploratory: Monitor and Compare the Gut Microbial Communities in Both Arms of the Trial
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.
Population: Due to lack of funding analysis could be be completed.
Other Pre-specified
Exploratory: Utility of a Patient Personalized Clinical Benefit (PPCB) Phone Based Application
Patient compliance rate of completing the PPCB application was calculated by the total percentage of completed questionnaires over expected questionnaires across all participants.
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.
Population: All patients were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab & Paricalcitol | Exploratory: Utility of a Patient Personalized Clinical Benefit (PPCB) Phone Based Application | 89.4 % of questionnaires completed |
| Pembrolizumab & Placebo | Exploratory: Utility of a Patient Personalized Clinical Benefit (PPCB) Phone Based Application | 92.8 % of questionnaires completed |