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

Brief summary public domain (ClinicalTrials.gov)

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 public domain (ClinicalTrials.gov)

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.

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

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.]. Count Of Participants, Participants. Pembrolizumab & Paricalcitol (n=9): 0; Pembrolizumab & Placebo (n=12): 2. Analysis, Pembrolizumab & Placebo: Risk Ratio (RR) 0 (95% CI 0 to NA); p=.31; Fisher Exact; superiority.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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.]. Count Of Participants, Participants. Abdominal bloating: Pembrolizumab & Paricalcitol (n=12): 1; Pembrolizumab & Placebo (n=12): 0. Abdominal pain: Pembrolizumab & Paricalcitol (n=12): 1; Pembrolizumab & Placebo (n=12): 2. ALT increase: Pembrolizumab & Paricalcitol (n=12): 2; Pembrolizumab & Placebo (n=12): 0. Alkaline phosphatase increase: Pembrolizumab & Paricalcitol (n=12): 1; Pembrolizumab & Placebo (n=12): 0. Anemia: Pembrolizumab & Paricalcitol (n=12): 0; Pembrolizumab & Placebo (n=12): 1. Arthralgia: Pembrolizumab & Paricalcitol (n=12): 2; Pembrolizumab & Placebo (n=12): 0. AST increase: Pembrolizumab & Paricalcitol (n=12): 2; Pembrolizumab & Placebo (n=12): 1. Creatinine increase: Pembrolizumab & Paricalcitol (n=12): 2; Pembrolizumab & Placebo (n=12): 0. Hypertension: Pembrolizumab & Paricalcitol (n=12): 0; Pembrolizumab & Placebo (n=12): 2. Hypophysitis: Pembrolizumab & Paricalcitol (n=12): 1; Pembrolizumab & Placebo (n=12): 0. Nausea: Pembrolizumab & Paricalcitol (n=12): 1; Pembrolizumab & Placebo (n=12): 0. Pruritis: Pembrolizumab & Paricalcitol (n=12): 1; Pembrolizumab & Placebo (n=12): 0. Uticaria: Pembrolizumab & Paricalcitol (n=12): 0; Pembrolizumab & Placebo (n=12): 1. Vomiting: Pembrolizumab & Paricalcitol (n=12): 1; Pembrolizumab & Placebo (n=12): 0.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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).]. Median, months (95% Confidence Interval). Pembrolizumab & Paricalcitol (n=12): 10.4 (2.9 to NA) [The upper bound of the confidence interval cannot be calculated because the upper bound did not fall below 50% by the end of the study.]; Pembrolizumab & Placebo (n=12): NA (2.5 to NA) [Median OS not be calculated for the pembrolizumab \& placebo group because the median has not yet been reached (only 4 deaths of 12 participants). The upper bound of the confidence interval cannot be calculated because the upper bound did not fall below 50% by the end of the study.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

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).].