Azacitidine + Entinostat for Advanced Breast Cancer

No longer recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Valproic acid

Disqualifiers: Pregnancy, Active infection, Heart failure, 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: 28 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of combining azacitidine and entinostat in treating advanced breast cancer. Azacitidine, a chemotherapy drug, stops tumor cells from growing, while entinostat blocks enzymes essential for cell growth. Together, these drugs might more effectively kill cancer cells. The trial seeks participants with advanced breast cancer that is either triple-negative or hormone-positive and who have not responded to previous treatments. Participants should have breast cancer that has spread and is either inoperable or cannot be surgically removed. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications to join the trial?

The trial requires that you stop certain medications before joining. Chemotherapy, hormone therapy, radiotherapy, and surgery must be stopped at least 3 weeks before registration, and some specific drugs like nitrosoureas, mitomycin C, trastuzumab, and bevacizumab must be stopped 6 weeks prior. However, bisphosphonate therapy and ovarian suppression therapy are allowed.

Is there any evidence suggesting that azacitidine and entinostat are likely to be safe for humans?

Research shows that the combination of azacitidine and entinostat has been tested in women with advanced hormone-resistant or triple-negative breast cancer. In these studies, most participants tolerated the treatment well. Some experienced side effects, but these were usually manageable.

Similar trials report side effects such as low blood cell counts, nausea, and tiredness. However, no unexpected safety problems emerged. This combination has also been studied in other types of cancer, providing more information about its safety.

The trial's advanced stage indicates that earlier research found the treatment to be fairly safe. It is important to discuss possible side effects with a healthcare provider to understand what might apply. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of azacitidine and entinostat for advanced breast cancer because it introduces a unique approach that could enhance treatment effectiveness. Unlike standard treatments that primarily target hormone receptors or HER2 proteins, this combination works by modulating gene expression and reversing abnormal gene silencing, potentially making cancer cells more susceptible to other therapies. Azacitidine is administered subcutaneously, and entinostat is taken orally, offering a convenient and potentially synergistic treatment option. By targeting the epigenetic landscape of cancer cells, this combination may offer a new way to combat resistance seen with traditional therapies.

What evidence suggests that azacitidine and entinostat might be an effective treatment for advanced breast cancer?

Research suggests that combining azacitidine and entinostat might help treat advanced breast cancer, particularly in patients whose cancer doesn't respond to hormone treatments or is triple-negative. In this trial, participants will receive azacitidine and entinostat as part of the treatment regimen. Azacitidine stops cancer cells from growing, while entinostat blocks enzymes that aid their growth. However, some studies showed that this combination hasn't led to major improvements in patients. Despite this, researchers continue to explore its potential benefits. Ongoing research may provide more information about its effectiveness. ^{1 2 6 7 8}

Who Is on the Research Team?

Vered Stearns

Principal Investigator

Johns Hopkins University/Sidney Kimmel Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with advanced breast cancer that's either triple-negative or hormone-positive/HER2-. They must have tried certain treatments already and be in good enough health to participate. Patients need to provide tissue and blood samples, not be pregnant, use contraception if they can have children, and agree to follow-up visits.

Inclusion Criteria

I can have a biopsy taken from my tumor, or I've tried but it was unsuccessful.

My breast cancer is advanced, cannot be removed by surgery, and is either triple-negative or hormone positive/HER2-.

I am fully active or can carry out light work.

Exclusion Criteria

You are currently taking any other experimental medications.

I don't have any severe illnesses that would affect my participation in the study.

I started hormone therapy less than 3 weeks ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive azacitidine subcutaneously on days 1-5 and 8-10, and entinostat orally on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

Multiple visits per cycle for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3-6 months for up to 3 years.

Up to 3 years

Follow-up visits every 3-6 months

Extension

Participants with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.

What Are the Treatments Tested in This Trial?

Interventions

• Azacitidine
• Entinostat

Trial Overview The study tests azacitidine combined with entinostat on patients with advanced breast cancer. Azacitidine is a chemotherapy drug that kills or stops tumor cells from dividing. Entinostat blocks enzymes needed for cell growth. The hope is this combination will kill more tumor cells.

How Is the Trial Designed?

Group I: Treatment (entinostat and azacitidine) Experimental Treatment 4 Interventions

Patients receive azacitidine SC on days 1-5 and 8-10, and entinostat PO on days 3 and 10. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with progressive disease may continue azacitidine and entinostat in combination with hormonal therapy, at treating physician discretion, or undergo event monitoring.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27979916/

A Phase II National Cancer Institute/Stand Up to Cancer Study We conducted a multicenter phase II study of 5-azacitidine and entinostat in women with advanced hormone-resistant or triple-negative breast cancer (TNBC).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5457329/

Combination Epigenetic Therapy in Advanced Breast ... We conducted a multicenter phase II study of 5-azacitidine (AZA) and entinostat in women with advanced hormone-resistant or triple-negative breast cancer (TNBC ...

3. researchgate.net researchgate.net/publication/311703794_Combination_Epigenetic_Therapy_in_Advanced_Breast_Cancer_with_5-Azacitidine_and_Entinostat_A_Phase_II_National_Cancer_InstituteStand_Up_to_Cancer_Study

Combination Epigenetic Therapy in Advanced Breast ... A phase II clinical trial combining 5-Aza and histone deacetylase inhibitor (HDACi), entinostat failed to demonstrate significant clinical ...

4. pure.johnshopkins.edu pure.johnshopkins.edu/en/publications/combination-epigenetic-therapy-in-advanced-breast-cancer-with-5-a

Combination epigenetic therapy in advanced breast cancer ... We conducted a multicenter phase II study of 5-azacitidine and entinostat in women with advanced hormone-resistant or triple-negative breast ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01935947

Azacitidine and Entinostat Before Chemotherapy in ... This randomized phase II trial studies how well azacitidine and entinostat before chemotherapy works in treating patients with non-small cell lung cancer ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01935947

Study Details | NCT01935947 | Azacitidine and Entinostat ... This randomized phase II trial studies how well azacitidine and entinostat before chemotherapy works in treating patients with non-small cell lung cancer ...

7. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/1756-8722-2-22

New clinical developments in histone deacetylase inhibitors ... In this review we summarize novel histone deacetylase inhibitors and new regimens from clinical trials for epigenetic therapy of cancer.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2817034/

5-azacitidine prolongs overall survival in patients with ... Treatment with hypomethylating agents significantly improved overall survival (hazard ratio 0.72, 95% confidence interval 0.60–0.85, three trials) and time to ...