What side effects are associated with this type of intervention?

Azeliragon, which targets the RAGE pathway, is being studied for its potential to decrease chemotherapy-related cognitive decline and cardiotoxicity. While specific side effects of Azeliragon are not well-documented, general treatments for CRCI, including chemotherapy and targeted therapies, often result in side effects such as fatigue, nausea, vomiting, and cognitive issues like memory loss and difficulty concentrating. Additionally, some targeted therapies may cause specific side effects like skin reactions, gastrointestinal disturbances, and hematologic abnormalities.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments targeting the RAGE pathway for Cancer-Related Cognitive Impairment (CRCI). Azeliragon is being studied for its potential to decrease chemotherapy-related cognitive decline by targeting the RAGE pathway. Broadly, treatments for CRCI often focus on managing symptoms through cognitive rehabilitation, lifestyle modifications, and addressing contributing factors such as fatigue and depression.

What other types of research exist?

Currently, there are no specific alternatives to Azeliragon targeting the RAGE pathway mentioned in the provided context. However, ongoing research into other pathways and mechanisms, such as the Ras-MAPK signaling pathway inhibitor TLN-4601 for glioblastoma, may offer insights into novel treatments for cancer-related cognitive impairment. Patients should discuss with their oncologist about emerging therapies and clinical trials that may be relevant to their condition.

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Azeliragon + Chemotherapy for Breast Cancer (RAGE Trial)

Phase 1 & 2

Recruiting

Led By Candace Mainor, MD

Research Sponsored by Georgetown University

Eligibility Criteria Checklist

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

Must have

Age ≥18 years.

Patients must have had no prior chemotherapy/radiotherapy/or systemic therapy for early stage breast cancer, or any other malignancy

Must not have

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.

Patients who have had prior chemotherapy, radiotherapy, systemic therapy, or hormonal therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up cohort 1 and 4: cycle 3 and cycle 4, day 1 and day 2 of 14 day cycle; cohort 2 and 3:cycle 5 and cycle 6, day 1 and day 2 of 21 day cycle

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing azeliragon, a drug that may reduce heart and brain damage caused by chemotherapy. It targets patients receiving anthracycline chemotherapy, which can harm the heart and cause cognitive decline. Azeliragon works by blocking a pathway involved in inflammation and cell damage. It is being studied as a potential treatment to slow disease progression in patients with mild Alzheimer's Disease.

Who is the study for?

This trial is for women with early-stage breast cancer (stage I-III) who are about to start chemotherapy and have not had previous treatments for any cancer. They must be over 18, have good organ function, no severe neurological or psychiatric conditions that could affect consent, and agree to use contraception. HIV-positive patients on effective therapy can join.

What is being tested?

The study tests azeliragon's ability to reduce heart damage from certain chemotherapies (TCHP, ddAC/ddT, TC) and its safety when combined with these treatments. It aims to see if blocking the RAGE pathway lessens heart toxicity and cognitive decline caused by chemotherapy.

What are the potential side effects?

While specific side effects of azeliragon in combination with chemotherapy aren't detailed here, potential risks include those commonly associated with chemo such as fatigue, nausea, increased infection risk; plus any unknown risks of azeliragon itself.

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 have not had chemotherapy, radiotherapy, or systemic therapy for early stage breast cancer or any other cancer.

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I have no history of stroke, head injury, or diseases like Alzheimer's.

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I have stage I-III breast cancer and will receive chemotherapy.

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I can take care of myself but might not be able to do heavy physical work.

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I have HIV, HBV, or HCV but my viral load is undetectable with treatment.

Exclusion Criteria

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

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

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I have had chemotherapy, radiotherapy, systemic therapy, or hormonal therapy before.

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I am not pregnant or breastfeeding.

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My breast cancer is at stage IV.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ cohort 1 and 4: cycle 3 and cycle 4, day 1 and day 2 of 14 day cycle; cohort 2 and 3:cycle 5 and cycle 6, day 1 and day 2 of 21 day cycle

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~cohort 1 and 4: cycle 3 and cycle 4, day 1 and day 2 of 14 day cycle; cohort 2 and 3:cycle 5 and cycle 6, day 1 and day 2 of 21 day cycle

This trial's timeline: 3 weeks for screening, Varies for treatment, and cohort 1 and 4: cycle 3 and cycle 4, day 1 and day 2 of 14 day cycle; cohort 2 and 3:cycle 5 and cycle 6, day 1 and day 2 of 21 day cycle for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Body Weight Changes

Incidence of unacceptable toxicity

Secondary study objectives

Pharmacokinetic (PK) assessment: AUC0-INF

Pharmacokinetic (PK) assessment: AUC0-last

Pharmacokinetic (PK) assessment: AUC0-tau

+3 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Cohort 4: TTP488 (Azeliragon) co-administered with chemotherapy regimen that includes ddACExperimental Treatment2 Interventions

given at the end of the chemotherapy plan \[can include: (1)weekly carboplatin + paclitaxel + pembrolizumab followed by pembrolizumab + dose dense doxorubicin and cyclophosphamide; (2) weekly carboplatin + paclitaxel followed by dose dense doxorubicin and cyclophosphamide; (3) weekly or dose dense paclitaxel followed by dose dense doxorubicin and cyclophosphamide\] Cohort 4: On day 7 of cycle 3, twelve capsules of azeliragon taken daily for 6 days, and then four capsules of Azeliragon each day continuously through the end of that cycle of chemotherapy, extending into Cycle 4 Day 2 (C4D2).

Group II: Cohort 3: TTP488 (Azeliragon) co-administered with TCHPExperimental Treatment2 Interventions

TCHP: docetaxel, carboplatin, trastuzumab, and pertuzumab Cohort 3: Cycle 5 Day 14 (C5D14), take twelve capsules of azeliragon daily for 6 days, then four capsules of Azeliragon each day continuously through the end of that cycle of chemotherapy, extending into Cycle 6 Day 2 (C6D2).

Group III: Cohort 2: TTP488 (Azeliragon) co-administered with TCExperimental Treatment2 Interventions

TC: docetaxel and cyclophosphamide Cohort 2a (6 cycles): Cycle 5 Day 14 (C5D14), take twelve capsules of azeliragon daily for 6 days, then four capsules of Azeliragon each day continuously through the end of that cycle of chemotherapy, extending into Cycle 6 Day 2 (C6D2). Cohort 2b (4 cycles): Cycle 3 Day 14 (C3D14), take twelve capsules of azeliragon daily for 6 days, then four capsules of Azeliragon each day continuously through the end of that cycle of chemotherapy, extending into Cycle 4 Day 2 (C4D2).

Group IV: Cohort 1: TTP488 (Azeliragon) co-administered with dose dense paclitaxel (ddAC/ddT)Experimental Treatment2 Interventions

Cohort 1: On day 7 of cycle 3, twelve capsules of azeliragon taken daily for 6 days, and then four capsules of Azeliragon each day continuously through the end of that cycle of chemotherapy, extending into Cycle 4 Day 2 (C4D2).

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

2002

Completed Phase 3

~1750

0 / 10Eligibility 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

Cancer-Related Cognitive Impairment (CRCI) treatments often target pathways involved in inflammation and oxidative stress, which are believed to contribute to cognitive decline. Azeliragon, for example, inhibits the Receptor for Advanced Glycation End-products (RAGE) pathway, which is implicated in neuroinflammation and neuronal damage. By blocking this pathway, Azeliragon aims to reduce inflammation and protect cognitive function. This is crucial for CRCI patients as it addresses the underlying mechanisms of cognitive decline, potentially improving their quality of life and ability to function daily.

Network meta-analyses for EGFR mutation-positive non-small-cell lung cancer: systematic review and overview of methods and shortcomings.Anticancer drugs repurposed for Alzheimer's disease: a systematic review.A Clinical Evaluation of Enzalutamide in Metastatic Castration-Sensitive Prostate Cancer: Guiding Principles for Treatment Selection and Perspectives on Research.