Azacitidine and Pembrolizumab in Pancreatic Cancer
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|ClinicalTrials.gov Identifier: NCT03264404|
Recruitment Status : Recruiting
First Posted : August 29, 2017
Last Update Posted : October 3, 2019
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.
Primary objective: To evaluate the progression-free survival per RECIST 1.1.
- Safety Objective: To determine the safety and tolerability of induction therapy with azacitidine followed by pembrolizumab in advanced pancreatic cancer.
- To evaluate the objective response rate (ORR), duration of response (DOR), disease control rate (DCR), and time to progression (TTP) per RECIST 1.1, and overall survival (OS).
|Condition or disease||Intervention/treatment||Phase|
|Pancreas Cancer||Drug: Pembrolizumab Drug: Azacitidine||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Open-Label, Single-Center Study Evaluating Safety and Efficacy of Pembrolizumab Following Induction With the Hypomethylating Agent Azacitidine in Patients With Advanced Pancreatic Cancer After Failure of First-Line Therapy|
|Actual Study Start Date :||October 1, 2017|
|Estimated Primary Completion Date :||March 2020|
|Estimated Study Completion Date :||September 2020|
Patients with advanced pancreatic cancer will receive pembrolizumab with the hypomethylating agent azacitidine.
Pembrolizumab 200 mg IV every 3 weeks until progression
Other Name: Keytruda
50 mg/m2 subcutaneous daily for 5 days every 28 days
Other Name: Vidaza
- Progression-Free Survival (PFS) [ Time Frame: 24 months ]PFS is defined as the time from the first day of trial treatment to the first documented disease progression per RECIST 1.1 or death due to any cause, whichever occurs first.
- Objective Response Rate (ORR) [ Time Frame: 24 months ]ORR is defined as the proportion of the subjects in the analysis population who have a complete response (CR) or partial response (PR). Responses are based on assessments per RECIST 1.1.
- Duration of Response (DOR) [ Time Frame: 24 months ]For subjects who demonstrate CR or PR, based on assessments per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
- Disease Control Rate (DCR) [ Time Frame: 24 months ]DCR is defined as the percentage of subjects who have achieved CR, PR, or stable disease (SD) based on assessments per RECIST 1.1.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03264404
|Contact: Lisa Olmos, RN||(212) firstname.lastname@example.org|
|United States, New York|
|Columbia University Irving Medical Center||Recruiting|
|New York, New York, United States, 10032|
|Contact: Rachael A. Safyan, MD email@example.com|
|Principal Investigator: Rachael A. Safyan, MD|
|Principal Investigator:||Rachael A. Safyan, MD||Columbia University|