What is the mechanism of action of this treatment?

Common treatments for breast cancer include chemotherapy, hormone therapy, targeted therapy, and immunotherapy. Chemotherapy works by killing rapidly dividing cells, hormone therapy blocks hormones that fuel certain cancers, targeted therapy attacks specific cancer cell molecules, and immunotherapy boosts the immune system to fight cancer. Low dose azacitidine, an epigenetic modulator, works by altering the expression of genes involved in cancer progression. Understanding these mechanisms helps patients and doctors choose the most effective treatment based on the cancer's specific characteristics, potentially improving outcomes and minimizing side effects.

What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those involving epigenetic modulation like low-dose azacitidine, include hypomethylating agents and other chemotherapeutic drugs. The known side effects of these treatments can include cytopenias (reduction in blood cell counts), febrile neutropenia (fever with low white blood cell count), gastrointestinal symptoms (nausea, vomiting, diarrhea), fatigue, and potential liver and kidney function abnormalities. Patients may also experience increased susceptibility to infections and require hospitalization for neutropenic fever. Growth factor support and dose adjustments are often necessary to manage these side effects.

What prior FDA approvals exist?

Currently, there are no specific FDA approvals for the use of low-dose azacitidine or similar epigenetic modulation therapies in the treatment of breast cancer. The trial mentioned is investigating the potential of low-dose azacitidine in high-risk early-stage breast cancer, focusing on its effect on tumor-infiltrating lymphocytes. Broadly, FDA-approved treatments for breast cancer include hormone therapies (e.g., tamoxifen, aromatase inhibitors), chemotherapy (e.g., doxorubicin, paclitaxel), targeted therapies (e.g., trastuzumab, pertuzumab), and immunotherapies (e.g., pembrolizumab).

What other types of research exist?

Promising novel alternatives to Low Dose Azacitidine for breast cancer patients include targeted therapies such as PARP inhibitors (e.g., olaparib, talazoparib) for BRCA-mutated cancers, CDK4/6 inhibitors (e.g., palbociclib, ribociclib) for HR-positive, HER2-negative breast cancer, and immunotherapy agents like pembrolizumab for PD-L1 positive triple-negative breast cancer. Additionally, antibody-drug conjugates such as trastuzumab deruxtecan for HER2-positive breast cancer are also emerging as effective treatments.

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Anti-metabolites

Low Dose Azacitidine for Early Stage Breast Cancer (BRE-04 Trial)

Phase 2

Recruiting

Led By Vijayakrishna Krishnamurthy Gadi, MD, PhD

Research Sponsored by University of Illinois at Chicago

Eligibility Criteria Checklist

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

Must have

Age ≥ 18 years of age at time of consent

ECOG 0, 1, or 2

Must not have

Previous anti-cancer treatment (cytotoxic chemotherapy, immunotherapy, biologic therapy, radiotherapy directed towards the primary breast tumor and/or ipsilateral axillary lymph nodes or investigational agents) with therapeutic intent for the current breast cancer

Active infection requiring systemic therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing if low dose azacitidine can help the immune system fight high-risk early stage breast cancer. The treatment aims to increase immune cells that attack cancer cells. It targets patients whose cancer is more likely to return or spread.

Who is the study for?

This trial is for adults with high-risk early stage breast cancer that hasn't spread far and hasn't been treated yet. Eligible patients have tumors over 1cm, are not pregnant or breastfeeding, and can follow the study plan. They should be in good health overall without serious illnesses that could interfere with the trial.

What is being tested?

The trial tests low dose Azacitidine's effect on immune cells within breast tumors. Researchers will compare these immune cell counts before and after treatment to see if there's a change.

What are the potential side effects?

While specific side effects of low dose Azacitidine in this context aren't listed, common ones include nausea, fatigue, bruising or bleeding more easily due to lower blood cell counts, and increased risk of infection.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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I can take care of myself and am up and about more than half of my waking hours.

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My breast cancer is confirmed and at an early to mid-stage, without distant spread.

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My breast cancer is triple-negative, ER-positive with high risk, or HER2-positive.

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My breast tumor is larger than 1cm.

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My cancer has not spread to distant parts of my body.

Exclusion Criteria

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

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I have had treatments like chemotherapy or radiation for my current breast cancer.

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I am currently on medication for an infection.

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I do not have uncontrolled HIV/AIDS or active hepatitis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 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

Change in tumor infiltrating lymphocytes (TILs) count in primary tumors from patients with high-risk early stage breast cancer following low-dose azacitidine therapy.

Secondary study objectives

Clinical response (change Ki67 and tumor size) of primary tumor following treatment with low dose azacitidine therapy

Disease Free Survival (DFS)

Overall Survival (OS)

+2 more

Side effects data

From 2007 Phase 3 trial • 358 Patients • NCT00071799

67%

Thrombocytopenia

65%

Neutropenia

50%

Constipation

48%

Nausea

48%

Anaemia

43%

Injection site erythema

29%

Injection site reaction

27%

Vomiting

26%

Pyrexia

24%

Fatigue

22%

Diarrhoea

19%

Nasopharyngitis

19%

Cough

18%

Injection site pain

18%

Leukopenia

17%

Acute myeloid leukaemia

15%

Asthenia

15%

Dyspnoea

15%

Epistaxis

14%

Headache

14%

Anorexia

13%

Oedema peripheral

12%

Abdominal pain

12%

Haematoma

11%

Pneumonia

11%

Febrile neutropenia

11%

Transfusion reaction

11%

Petechiae

11%

Pruritus

10%

Oral herpes

10%

Dizziness

10%

Rash

Arthralgia

Back pain

Bronchitis

Insomnia

Upper respiratory tract infection

Hypertension

Weight decreased

Contusion

Haemorrhoids

Erythema

Urinary tract infection

Lethargy

Abdominal pain upper

Muscle spasms

Gingival bleeding

Injection site rash

Influenza

Oral candidiasis

Rhinitis

Pain in extremity

Hypotension

Dyspepsia

Injection site haematoma

Hypokalaemia

Haematuria

Pharyngolaryngeal pain

Chest pain

Mouth ulceration

Musculoskeletal pain

Depression

Oedema

Pharyngitis

Anxiety

Ecchymosis

Injection site bruising

Injection site induration

Dyspnoea exertional

Pain

Bone pain

Alopecia

Skin lesion

Conjunctival haemorrhage

Respiratory tract infection

Tachycardia

Productive cough

Stomatitis

Dry mouth

Gingivitis

Chills

Sinusitis

Sepsis

Fall

Alanine aminotransferase increased

Sleep disorder

Gastritis

Neutropenic sepsis

Purpura

Catheter site haematoma

Muscular weakness

Nasal congestion

Hyperuricaemia

Cardiac failure

Bronchopneumonia

Lymphopenia

Gastrooesophageal reflux disease

Rectal haemorrhage

General physical health deterioration

Pallor

Septic shock

Myelodysplastic syndrome

Cerebral haemorrhage

Pitting oedema

Procedural pain

Syncope

Gastrointestinal pain

Anal haemorrhage

Perianal abscess

Ventricular tachycardia

Lung infection

Subileus

Myocardial infarction

Oral soft tissue disorder

Catheter site haemorrhage

Hypophosphataemia

Renal colic

Strabismus

Cellulitis

Eye Haemorrhage

Peripheral vascular disorder

Enterobacter infection

Haemorrhoidal haemorrhage

Gastrointestinal haemorrhage

Tooth abscess

Food poisoning

Intestinal haemorrhage

Corynebacterium infection

Psychotic disorder

Clostridium difficile colitis

Delirium

Musculoskeletal chest pain

Pancytopenia

Endophthalmitis

Haematemesis

Mouth haemorrhage

Tooth disorder

Meningitis

Subcutaneous abscess

Confusional state

Benign prostatic hyperplasia

Hypoxia

Abdominal discomfort

Atrial fibrillation

Angle closure glaucoma

Conjunctivitis

Fungal skin infection

Angina pectoris

Herpes zoster

Salmonella sepsis

Subdiaphragmatic abscess

Blood lactate dehydrogenase increased

Ocular hyperaemia

Catheter site pain

Joint swelling

Transient ischaemic attack

Pulmonary embolism

Pleural effusion

Cardiac failure acute

Vertigo

Oesophageal carcinoma

Myopia

Retinal artery occlusion

Squamous cell carcinoma of skin

Haemoptysis

Lung infiltration

Respiratory failure

Pulmonary oedema

Pulmonary fibrosis

Hallucination

Colitis ulcerative

Injection site nodule

Bacteraemia

Bile duct stone

Hepatic function abnormal

Fungal sepsis

Gasteroenteritis

Gasteroenteritis salmonella

Laryngopharyngitis

Lobar pneumonia

Lower respiratory tract infection

Pulmonary tuberculosis

Sialoadenitis

Splenic abscess

Staphylococcal bacteraemia

Clavicle fracture

Hip fracture

Traumatic intracranial haemorrhage

Diabetes mellitus

Colon cancer

Lung adenocarcinoma

Neoplasm prostate

Urinary tract neoplasm

Coma

Haemorrhage intracranial

Renal failure

Urethral stenosis

Acute pulmonary oedema

Acute respiratory failure

Hypoalbuminaemia

Hyponatraemia

Lymphadenopathy

Gingival pain

Generalised oedema

Catheter related infection

Neck pain

Dermatitis allergic

Rash macular

Urticaria

Bone marrow failure

Pericardial effusion

Hypothyroidism

Retinal Haemorrhage

Retinal tear

Abdominal wall abscess

Abscess neck

Ear infection

Enterobacter bacteraemia

Mucormycosis

Neutropenic infection

Parotitis

Pneumonia fungal

Synovial rupture

Osteoporosis

Myelofibrosis

Loss of consciousness

Urinary retention

Pneumonitis

Actinic keratosis

Aortic aneurysm

Circulatory collapse

Bronchopulmonary aspergillosis

Bradycardia

Aphthous stomatitis

Mucosal inflammation

Staphylococcal infection

Viral upper respiratory tract infection

Scratch

Thermal burn

Aspartate aminotransferase increased

Hypocalcaemia

Bursitis

Sinus headache

Chromaturia

Proteinuria

Pleurisy

Rash papular

Rash pruritic

100%

80%

60%

40%

20%

Study treatment Arm

Azacitidine

Low-dose Cytarabine

Best Supportive Care Only

Standard Chemotherapy

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: Single arm with previously untreated high risk early stage breast cancerExperimental Treatment1 Intervention

All participants will receive azacitidine 50mg/m2 SC daily for five consecutive days.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Azacitidine

2012

Completed Phase 3

~1440

0 / 9Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for breast cancer include chemotherapy, hormone therapy, targeted therapy, and immunotherapy. Chemotherapy works by killing rapidly dividing cells, hormone therapy blocks hormones that fuel certain cancers, targeted therapy attacks specific cancer cell molecules, and immunotherapy boosts the immune system to fight cancer. Low dose azacitidine, an epigenetic modulator, works by altering the expression of genes involved in cancer progression. Understanding these mechanisms helps patients and doctors choose the most effective treatment based on the cancer's specific characteristics, potentially improving outcomes and minimizing side effects.

Indications and limitations of third-generation aromatase inhibitors.Gemcitabine.