Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03264404 |
| Other study ID # |
AAAR3554 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
October 1, 2017 |
| Est. completion date |
January 31, 2024 |
Study information
| Verified date |
July 2023 |
| Source |
Columbia University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to determine the effectiveness of combining immune therapy,
pembrolizumab, with a hypomethylating agent, azacitidine, for pancreatic cancer. People who
have advanced pancreatic cancer with disease progression on first-line therapy are usually
treated with a second chemotherapy regimen. However, there is no single accepted chemotherapy
regimen and national guidelines recommend chemotherapy or clinical trial participation. In
this study, all study subjects will receive a combination of immune therapy (every 3 weeks)
and a hypomethylating agent (every 4 weeks). To date, studies have shown that combining a
hypomethylating agent with chemotherapy or immune therapy may benefit patients across
different solid tumor types including pancreatic cancer. Preclinical data in a mouse model of
pancreatic cancer demonstrates improvement in survival with the combination of a
hypomethylating agent and immune therapy. However, the use of single agent hypomethylating
agent or immune therapy has not been shown to be effective in patients with pancreatic
cancer. The one exception, to date, is the use of immune therapy in those individuals with a
particular genetic feature known as mismatch repair deficiency and microsatellite
instability. The combination of immune therapy and a hypomethylating agent has not been
studied in human subjects and is not approved by the FDA for use in pancreatic cancer.
This is a non-randomized, single-center, open-label trial of pembrolizumab and azacitidine in
subjects with locally advanced or metastatic pancreatic adenocarcinoma. Approximately 31
individuals will be asked to participate in this study.
Description:
Pancreatic ductal adenocarcinoma (PDA) has the worst prognosis of any major malignancy in the
United States and, unlike other common cancers, annual deaths from PDA are rising. Despite
recent advances, cytotoxic chemotherapy for PDA has been disappointing. Even among the small
subset of patients who are suitable for surgical resection at the time of diagnosis, complete
resection is followed by recurrence in majority of patients without further systemic therapy.
Thus all PDA patients require systemic chemotherapy and more effective regimens are urgently
needed.
Combination chemotherapy is effective in controlling disease and prolonging survival in
patients with advanced pancreatic cancer. Despite recent successful phase 3 studies in the
first-line setting, there is no defined second-line treatment for patients who experience
disease progression following first-line therapy. Consensus guidelines (such as the National
Comprehensive Cancer Network (NCCN) guidelines) recommend clinical trial participation in
this setting.
The investigators' pre-clinical data suggests that decitabine treatment in the KPC model of
pancreatic cancer leads to a significant up-regulation of interferon-related genes and a
polarization of the infiltrating immune cells. Based on these results, the investigators have
evaluated the effect of single agent decitabine or anti-PD1H (a homologue of PD1 with very
similar function and expression pattern) compared to combination therapy (treatment with
decitabine followed by PD1H blockade). The investigators' preliminary results showed minimal
effect of either agent alone on tumor growth but marked decrease in tumor progression in the
combination arm. These results form the foundation of this phase II study.
This study will treat patients with the combination of azacitidine and pembrolizumab. A
direct comparison between azacitidine and decitabine in terms of efficacy within a controlled
clinical trial has not been performed thus far. In randomized myelodysplastic syndrome (MDS)
trials, the remission rates were similar for azacitidine and decitabine but the overall
survival in the experimental arm was significantly shorter in the decitabine trial compared
to the azacitidine trial. A primary reason to utilize azacitidine in this setting is our
desire to amply reduced dose therapy with the goal of maintaining subjects on therapy
Low-dose azacitidine is being tested in phase I/II clinical trials for advanced solid
tumors-mainly colorectal cancer, small-cell lung carcinomas, ovarian cancer, and breast
cancer.
