RECRUITING

RAGE Inhibition to Decrease Cardiotoxicity in Women With Early Breast Cancer

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a pilot study to evaluate the effects of azeliragon to decrease cardiac toxicity from chemotherapy and the safety of azelirgaon when given with chemotherapy. The Investigators hypothesize that there will be no significant interaction with Azeliragon and chemotherapy and that targeting the RAGE pathway will decrease anthracycline related cardiotoxicity and chemotherapy related cognitive decline.

Official Title

RAGE Inhibition to Decrease Cancer Therapy Related Cardio Toxicity in Women With Early Breast Cancer

Quick Facts

Study Start:2023-06-06

Study Completion:2024-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05256745

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Patients must have clinical or pathologic stage I-III, histologically confirmed breast cancer, with any ER (estrogen-receptor), PR (progesterone receptors), or HER2 (human epidermal growth factor receptor 2) status who are planned to receive chemotherapy in the adjuvant or neoadjuvant setting. 2. Patients must have had no prior chemotherapy/radiotherapy/or systemic therapy for early stage breast cancer, or any other malignancy 3. Age ≥18 years. 4. ECOG (Eastern Cooperative Oncology Group) performance status ≤2 (Karnofsky ≥60%, see Appendix D). 5. Patients must have normal organ and marrow function as defined below: 1. Leukocytes ≥3,000/mcL (microliter) 2. Absolute neutrophil count ≥1,500/mcL 3. Platelets ≥100,000/mcL 4. Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN) 5. AST(SGOT) (aspartate transaminase)/ALT(SGPT) (alanine aminotransferase) ≤1.5 × institutional ULN 6. Glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. 6. Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial. If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated. If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load. 7. No pre-existing neurodegenerative disease or impairment, including history of CVA (cerebrovascular accident), or head injury. 8. No psychiatric disorders which could interfere with their ability to consent. (Allowed psychiatric disorders may include but are not limited to: anxiety, depression, obsessive compulsive disorder, ADHD; as long as the disorder does not affect the ability to consent). Any other psychiatric disorders should be discussed with the Principal Investigator (PI) and will be allowed at the discretion of the PI. 9. The effects of azeliragon on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. 10. Ability to understand and the willingness to sign a written informed consent document.	1. Patients who have had prior chemotherapy, radiotherapy, systemic therapy, or hormonal therapy 2. Patients with Stage IV breast cancer 3. Patients who are receiving any other investigational agents. 4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to azeliragon, or the standard of care chemotherapy assigned, including: docetaxel, cyclophosphamide, carboplatin, doxorubicin, paclitaxel, trastuzumab, pertuzumab, pembrolizumab. 5. Patients receiving any medications or substances that are strong CYP2C8 inhibitors are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. Subjects who discontinue a strong CYP2C8 inhibitor must have discontinued the drug for at least 5 days or 5 half-lives of the drug, whichever is longer, before the first dose of study drug. 6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, neurogenerative disease/impairment, or psychiatric illness/social situations that would limit compliance with study requirements. 7. Pregnant women are excluded from this study as the risks of azeliragon to a fetus are unknown. There is unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azeliragon; breastfeeding should be discontinued if the mother is treated with azeliragon. These potential risks may also apply to other agents used in this study. 8. History of cancer within the last 5 years except adequately treated cervical carcinoma-in-situ, or cutaneous basal cell or squamous cell cancer.

Inclusion Criteria

Exclusion Criteria

1. Patients must have clinical or pathologic stage I-III, histologically confirmed breast cancer, with any ER (estrogen-receptor), PR (progesterone receptors), or HER2 (human epidermal growth factor receptor 2) status who are planned to receive chemotherapy in the adjuvant or neoadjuvant setting.
2. Patients must have had no prior chemotherapy/radiotherapy/or systemic therapy for early stage breast cancer, or any other malignancy
3. Age ≥18 years.
4. ECOG (Eastern Cooperative Oncology Group) performance status ≤2 (Karnofsky ≥60%, see Appendix D).
5. Patients must have normal organ and marrow function as defined below:
1. Leukocytes ≥3,000/mcL (microliter)
2. Absolute neutrophil count ≥1,500/mcL
3. Platelets ≥100,000/mcL
4. Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN)
5. AST(SGOT) (aspartate transaminase)/ALT(SGPT) (alanine aminotransferase) ≤1.5 × institutional ULN
6. Glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
6. Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial. If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated. If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load.
7. No pre-existing neurodegenerative disease or impairment, including history of CVA (cerebrovascular accident), or head injury.
8. No psychiatric disorders which could interfere with their ability to consent. (Allowed psychiatric disorders may include but are not limited to: anxiety, depression, obsessive compulsive disorder, ADHD; as long as the disorder does not affect the ability to consent). Any other psychiatric disorders should be discussed with the Principal Investigator (PI) and will be allowed at the discretion of the PI.
9. The effects of azeliragon on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
10. Ability to understand and the willingness to sign a written informed consent document.

1. Patients who have had prior chemotherapy, radiotherapy, systemic therapy, or hormonal therapy
2. Patients with Stage IV breast cancer
3. Patients who are receiving any other investigational agents.
4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to azeliragon, or the standard of care chemotherapy assigned, including: docetaxel, cyclophosphamide, carboplatin, doxorubicin, paclitaxel, trastuzumab, pertuzumab, pembrolizumab.
5. Patients receiving any medications or substances that are strong CYP2C8 inhibitors are ineligible. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product. Subjects who discontinue a strong CYP2C8 inhibitor must have discontinued the drug for at least 5 days or 5 half-lives of the drug, whichever is longer, before the first dose of study drug.
6. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, neurogenerative disease/impairment, or psychiatric illness/social situations that would limit compliance with study requirements.
7. Pregnant women are excluded from this study as the risks of azeliragon to a fetus are unknown. There is unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azeliragon; breastfeeding should be discontinued if the mother is treated with azeliragon. These potential risks may also apply to other agents used in this study.
8. History of cancer within the last 5 years except adequately treated cervical carcinoma-in-situ, or cutaneous basal cell or squamous cell cancer.

Contacts and Locations

Study Contact

Lana Kheir

CONTACT

202-687-9016

lk814@georgetown.edu

Principal Investigator

Candace Mainor, MD

PRINCIPAL_INVESTIGATOR

Georgetown University

Study Locations (Sites)

Georgetown Lombardi Comprehensive Cancer Center

Washington, District of Columbia, 20007

United States

Medstar Washington Hospital Center

Washington, District of Columbia, 20010

United States

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601

United States

Collaborators and Investigators

Sponsor: Georgetown University

Candace Mainor, MD, PRINCIPAL_INVESTIGATOR, Georgetown University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-06

Study Completion Date2024-11

Study Record Updates

Study Start Date2023-06-06

Study Completion Date2024-11

Terms related to this study

Additional Relevant MeSH Terms

Cancer Related Cognitive Decline
Non-metastatic Breast Cancer