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Histone Deacetylase Inhibitor

Triple Therapy for Breast Cancer

Phase 1

Waitlist Available

Led By Roisin M Connolly

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Dose escalation: patients must have histologically or cytologically confirmed solid tumor malignancy that is metastatic or unresectable and for whom either standard curative or palliative measures do not exist or are no longer effective, or for whom anti-PD-L1/cytotoxic T-lymphocyte antigen (CTLA)-4 is appropriate

Dose expansion: patients must have histologically or cytologically confirmed invasive adenocarcinoma of the breast (human epidermal growth factor receptor 2 [HER2]-negative) that is locally advanced/metastatic and has progressed despite standard therapy; at least 1 prior chemotherapy regimen in the metastatic setting, and two lines of hormonal therapy (administered in the adjuvant or metastatic setting) for patients with hormone receptor-positive disease; NOTE: HER2-negativity will be defined per American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines; patients whose tumors have HER2 immunohistochemistry (IHC) 3+, in situ hybridization (ISH) >= 2.0, or average HER2 copy number >= 6.0 signals per cell are not eligible

Must not have

Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity; NOTE: subjects must have baseline oxygen/saturation level requirements as above

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that in the judgment of the investigator would limit compliance with study requirements

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing entinostat, nivolumab, and ipilimumab to see if they're effective and have manageable side effects in treating patients with metastatic or unresectable solid tumors or HER2-negative breast cancer.

Who is the study for?

Adults with solid tumors that are metastatic/unresectable or HER2-negative breast cancer that's advanced despite treatment. Must have had prior chemotherapy for metastatic breast cancer and hormone therapy if applicable. No active autoimmune diseases, untreated brain metastases, another recent malignancy, or need for immune suppressive drugs.

What is being tested?

The trial is testing the combination of entinostat (an HDAC inhibitor) with nivolumab and ipilimumab (monoclonal antibodies) to see if they can better treat patients with advanced cancers by inhibiting enzymes needed for cell growth and boosting the immune system's ability to fight cancer.

What are the potential side effects?

Potential side effects include reactions related to the immune system attacking normal organs, infusion-related reactions, fatigue, gastrointestinal issues like bowel perforation risk, blood disorders such as anemia or clotting problems, increased infection risk due to immunosuppression.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My cancer is advanced, cannot be surgically removed, and standard treatments haven't worked or aren't suitable.

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My breast cancer is advanced, HER2-negative, and didn't respond to standard treatments.

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I am 18 years old or older.

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My kidney function, measured by creatinine levels or clearance, is normal.

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My oxygen levels stay above 90% when I move around without needing extra oxygen.

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I am fully active or able to carry out light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have lung disease that causes symptoms or could affect lung toxicity treatment.

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I do not have any severe illnesses that would stop me from following the study's requirements.

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I am not taking valproic acid.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events of entinostat and nivolumab in combination with ipilimumab

Secondary study objectives

Changes in ratio of effector T cell (Teff) to regulatory T cell (Treg) in tumor biopsies

Disease control rate (expansion cohort of patients with advanced breast cancer)

Duration of overall response (expansion cohort of patients with advanced breast cancer)

+3 more

Other study objectives

CD86 gene polymorphisms as genetic determinants of immune mediated adverse events

Changes in candidate gene re-expression in malignant tissue, gene methylation silencing in circulating deoxyribonucleic acid (DNA) and malignant tissue pre and post-therapy

Changes in number of myeloid derived suppressor cells (MDSCs) in peripheral blood and tumor biopsies

+4 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (entinostat, nivolumab, ipilimumab)Experimental Treatment10 Interventions

Patients receive entinostat PO on days -14 and -7 and then weekly, nivolumab IV over 60 minutes on day 1 and then every 2 weeks, and ipilimumab IV over 90 minutes on day 1 and then every 6 weeks for 4 doses. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT as clinically indicated throughout the trial. Patients may undergo PET/CT or bone scan throughout the trial. Patients also undergo tissue biopsy and blood sample collection during screening and on the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Positron Emission Tomography

2011

Completed Phase 2

~2200

Biopsy

2014

Completed Phase 4

~1150