Azacitidine + Pembrolizumab for Pancreatic Cancer

Overseen By Research Nurse Navigator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Susan E. Bates

Must not be taking: Chemotherapy, Radiotherapy, others

Disqualifiers: Investigational agents, Herbal medicine, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for pancreatic cancer using two drugs: pembrolizumab, which boosts the immune system to fight cancer, and azacitidine (also known as Vidaza or 5-azacytidine), which can make cancer cells more vulnerable to treatment. The goal is to determine if this combination is more effective than standard treatments for individuals whose cancer has progressed after initial chemotherapy. It targets those with pancreatic cancer that has either spread or returned after initial treatment. Participants should have previously undergone chemotherapy with specific drugs like gemcitabine or 5-FU and experienced disease progression despite that. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have received chemotherapy or radiotherapy within 14 days before starting the study treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that combining two drugs, azacitidine and pembrolizumab, may help treat pancreatic cancer in mice. These studies found that this combination improved survival rates in the animals. While promising, this combination has not yet been tested in humans with pancreatic cancer. Azacitidine affects DNA, and pembrolizumab is a type of immune therapy. Both drugs have been used safely in other conditions. Azacitidine is usually well-tolerated for blood disorders, and pembrolizumab has been safely used in various cancers. However, since this specific combination hasn't been studied in people with pancreatic cancer, its tolerance in humans remains unknown. The trial under consideration is in an early phase, meaning researchers are still learning about the safety and effectiveness of this combination for pancreatic cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Azacitidine and Pembrolizumab for pancreatic cancer because it offers a novel approach compared to standard treatments like chemotherapy and surgery. Pembrolizumab is an immunotherapy drug that helps the immune system recognize and attack cancer cells, which is different from traditional methods that directly target cancer cells. Azacitidine, a hypomethylating agent, can make cancer cells more visible to the immune system, potentially enhancing the effectiveness of Pembrolizumab. This combination could provide a new avenue for treating pancreatic cancer by boosting the body's natural defenses against the disease.

What evidence suggests that this treatment might be an effective treatment for pancreatic cancer?

Studies have shown that combining azacitidine with an immune therapy drug like pembrolizumab can benefit patients with various solid tumors, including pancreatic cancer. Research in mice demonstrated improved survival with these treatments used together. While azacitidine or pembrolizumab alone has not been effective for pancreatic cancer, their combination appears promising based on early results. In this trial, participants will receive both azacitidine and pembrolizumab to enhance the body's immune response against cancer cells. Although still under investigation, early signs suggest this treatment could aid in treating pancreatic cancer. ^{1 2 4 6 7}

Who Is on the Research Team?

Susan E Bates, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced pancreatic cancer who've seen their disease get worse after first-line chemotherapy. They should have a life expectancy of more than 3 months, measurable disease, and be in good enough health to perform daily activities with little or no assistance. Those who've had recent chemo, radiotherapy, or participated in other drug studies can't join.

Inclusion Criteria

Be willing and able to provide written informed consent for the trial

You have been diagnosed with pancreatic ductal adenocarcinoma.

You are expected to live for more than 3 months.

Exclusion Criteria

Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy, or herbal/complementary oral or IV medicine within 2 weeks of the first dose of treatment

Has received chemotherapy or radiotherapy within 14 days of first dose of study medication

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of pembrolizumab (every 3 weeks) and azacitidine (every 4 weeks) for advanced pancreatic cancer

24 months

Visits every 3-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Pembrolizumab

Trial Overview The study tests combining pembrolizumab (an immune therapy given every 3 weeks) with azacitidine (a hypomethylating agent given every 4 weeks) on patients with advanced pancreatic cancer. It's an open-label trial where all participants receive the same treatment without being compared to a control group.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 2 Interventions

Patients with advanced pancreatic cancer will receive pembrolizumab with the hypomethylating agent azacitidine.

Azacitidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Vidaza for:

• Acute myeloid leukemia
• Chronic myelomonocytic leukemia
• Myelodysplastic syndromes

Approved in United States as Vidaza for:

• Myelodysplastic syndromes
• Chronic myelomonocytic leukemia

Approved in Canada as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Approved in Japan as Vidaza for:

• Myelodysplastic syndromes
• Acute myeloid leukemia

Who Is Running the Clinical Trial?

Susan E. Bates

Lead Sponsor

Trials

2

Recruited

70+

Rachael A Safyan, MD

Lead Sponsor

Trials

1

Recruited

40+

Ruth A. White, MD, PhD.

Lead Sponsor

Trials

1

Recruited

40+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03264404

Azacitidine and Pembrolizumab in 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.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.4158

Phase 2 study of azacitidine (AZA) plus pembrolizumab ... Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death with a 5-year survival rate of 10%.

3. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT03264404?keyword=%22First-line%22

Azacitidine and Pembrolizumab in Pancreatic Cancer ~Combination chemotherapy is effective in controlling disease and prolonging survival in patients with advanced pancreatic cancer. Despite recent successful ...

4. clin.larvol.com clin.larvol.com/trial-detail/NCT03264404

Azacitidine and Pembrolizumab in Pancreatic Cancer ... efficacy of pembrolizumab following induction with the hypomethylating agent azacitidine in patients with advanced pancreatic ... Download Trial Data.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02546986

Safety and Efficacy Study of CC-486 With MK-3475 to Treat ... The purpose of this study is to determine whether the combination therapy of CC-486 (oral azacitidine) and pembrolizumab provides improved patient outcomes ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10416846/

Neoadjuvant Immunotherapy for Localized Pancreatic ... Rational combination immunotherapy in addition to standard neoadjuvant therapy has the potential to improve outcomes in PDAC, but further ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02546986

NCT02546986 | Safety and Efficacy Study of CC-486 With ... The purpose of this study is to determine whether the combination therapy of CC-486 (oral azacitidine) and pembrolizumab provides improved patient outcomes ...