A SU2C Catalyst® Trial of a PD1 Inhibitor With or Without a Vitamin D Analog for the Maintenance of Pancreatic Cancer
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|ClinicalTrials.gov Identifier: NCT03331562|
Recruitment Status : Recruiting
First Posted : November 6, 2017
Last Update Posted : September 19, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Pancreatic Cancer Pancreas Adenocarcinoma Advanced Pancreatic Cancer Metastatic Pancreatic Cancer Metastatic Pancreatic Adenocarcinoma||Drug: Pembrolizumab Drug: paricalcitol Drug: placebo||Phase 2|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||24 participants|
|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|
|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|
|Actual Study Start Date :||December 27, 2017|
|Estimated Primary Completion Date :||May 15, 2019|
|Estimated Study Completion Date :||December 15, 2019|
Active Comparator: pembrolizumab & paricalcitol
pembrolizumab 200 mg IV q 3 weeks and paricalcitol 25 mcg IV 3 xs per week
pembrolizumab solution for infusion
Other Name: Keytruda
Paricalcitol solution for injection
Other Name: Zemplar
Placebo Comparator: pembrolizumab & placebo
pembrolizumab 200 mg IV q 3 weeks & placebo- normal saline IV 3 xs per week
pembrolizumab solution for infusion
Other Name: Keytruda
normal saline solution for injection
Other Name: placebo for paricalcitol
- 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
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03331562
|Contact: Jatan Clark, MBAemail@example.com|
|United States, Arizona|
|HonorHealth Research Institute||Recruiting|
|Scottsdale, Arizona, United States, 85258|
|Contact: Joyce Schaffer, RN 480-323-1339 firstname.lastname@example.org|
|Principal Investigator: Erkut Borazanci, MD|
|Principal Investigator: Gayle Jameson, ACNP-BC AOCN|
|United States, California|
|City of Hope National Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Isma Hafeez 626-218-5013 email@example.com|
|Principal Investigator: Vincent Chung, MD|
|United States, New Jersey|
|Atlantic Medical Group-Oncology Morristown Medical Center||Recruiting|
|Morristown, New Jersey, United States, 07962|
|Contact: Nancy Ginder, RN, BSN 973-971-6608|
|Principal Investigator: Angela Alistar, MD|
|Study Director:||Daniel D Von Hoff, MD, FACS||Translational Genomics Research Institute (TGen) An Affiliate of City of Hope|