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Cancer Related Cognitive DeclinePhase 1/2RAGENCT05256745

RAGE Inhibition to Decrease Cardiotoxicity in Women With Early Breast Cancer

A Phase 1/2 study testing TTP488, ddAC/ddT and TC in people with Cancer Related Cognitive Decline and Non-metastatic Breast Cancer, run by Georgetown University at 3 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
TTP488, ddAC/ddT and TC
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
3 sitesUnited States
Study dates
6 Jun 2023to Dec 2026
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • Chemotherapy regimens administered per USPI (United States Prescribing Information) label: i. Dose dense doxorubicin plus cyclophosphamide followed by paclitaxel (ddAC/ddT) for 8 cycles ii. Docetaxel plus cyclophosphamide (TC) for 4-6 cycles iii. Docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP)for 6 cycles iv. Chemotherapy regimen that includes ddAC, 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 dd paclitaxel followed by dose dense doxorubicin and cyclophosphamide]
  • Patients must have had no prior chemotherapy/radiotherapy/or systemic therapy for early stage breast cancer, or any other malignancy
  • Age ≥18 years.
  • ECOG (Eastern Cooperative Oncology Group) performance status ≤2 (Karnofsky ≥60%, see Appendix D).
  • Patients must have normal organ and marrow function as defined below:
Show all 17Show fewer
  • Leukocytes ≥3,000/mcL (microliter)
  • Absolute neutrophil count ≥1,500/mcL
  • Platelets ≥100,000/mcL
  • Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN)
  • AST(SGOT) (aspartate transaminase)/ALT(SGPT) (alanine aminotransferase) ≤1.5 × institutional ULN
  • Glomerular filtration rate (GFR) ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
  • 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.
  • No pre-existing neurodegenerative disease or impairment, including history of CVA (cerebrovascular accident), or head injury.
  • 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.
  • 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.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Patients who have had prior chemotherapy, radiotherapy, systemic therapy, or hormonal therapy
  • Patients with Stage IV breast cancer
  • Patients who are receiving any other investigational agents.
  • 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.
  • 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.
  • 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.
  • 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.
  • History of cancer within the last 5 years except adequately treated cervical carcinoma-in-situ, or cutaneous basal cell or squamous cell cancer.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Lana Kheir contact

202-687-9016

lk814@georgetown.edu

United States3 sites, 3 recruiting

  • John Theurer Cancer Center at Hackensack University Medical Center

    Hackensack, New Jersey, 07601

    Oncology Clinical Research Referral Office, 551-996-1777, OncologyResearchReferral@hmhn.org

    Deena Graham, MD

    Recruiting

  • Georgetown Lombardi Comprehensive Cancer Center

    Washington D.C., District of Columbia, 20007

    Lana Kheir, 202-687-9016, lk814@georgetown.edu

    Candace Mainor, MD

    Recruiting

  • Medstar Washington Hospital Center

    Washington D.C., District of Columbia, 20010

    Stacy Malloy, 202-877-9374, Stacy.K.Malloy@medstar.net

    Ami Chitalia, MD

    Recruiting

Other trials in United States

About this study

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

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.

Being tested
TTP488, ddAC/ddT, TC, TCHP, Chemotherapy regimen that includes ddAC

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TTP488Drug

    Also called Azeliragon

    Each Azeliragon capsule is 5mg, and is to be taken in the morning with food as indicated in each cohort.

  • ddAC/ddTDrug

    Also called Dose dense doxorubicin plus cyclophosphamide, dose dense paclitaxel

    Dose dense doxorubicin plus cyclophosphamide followed by paclitaxel (ddAC/ddT) for 8 cycles, administered per USPI (Unites States Prescribing Information) Label

  • TCDrug

    Also called Docetaxel plus cyclophosphamide

    Docetaxel plus cyclophosphamide (TC) for 4-6 cycles, administered per USPI (Unites States Prescribing Information) Label

  • TCHPDrug

    Also called Docetaxel, carboplatin, trastuzumab, and pertuzumab

    Docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP)for 6 cycles, administered per USPI (Unites States Prescribing Information) Label

  • Chemotherapy regimen that includes ddACDrug

    Also called Dose dense doxorubicin plus cyclophosphamide

    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, administered per USPI (Unites States Prescribing Information) Label

Study groups in NCT05256745
Study groupRoleWhat they receive
Cohort 1: TTP488 (Azeliragon) co-administered with dose dense paclitaxel (ddAC/ddT)ExperimentalCohort 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).
Receives: Drug: TTP488; Drug: ddAC/ddT
Cohort 2: TTP488 (Azeliragon) co-administered with TCExperimentalTC: 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).
Receives: Drug: TTP488; Drug: TC
Cohort 3: TTP488 (Azeliragon) co-administered with TCHPExperimentalTCHP: 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).
Receives: Drug: TTP488; Drug: TCHP
Cohort 4: TTP488 (Azeliragon) co-administered with chemotherapy regimen that includes ddACExperimentalgiven 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).
Receives: Drug: TTP488; Drug: Chemotherapy regimen that includes ddAC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of unacceptable toxicity

    Any Adverse Event (AE) considered unrelated to chemotherapy, underlying disease, disease progression, intercurrent illness or concomitant medications/therapies resulting in the inability to tolerate the cycle of chemotherapy

    Measured: 1 cycle (Cohort 1 and 4 each cycle is 14 days; Cohort 2 and 3 each cycle is 21 days)

  2. Incidence of severe AE graded according to the CTCAE v.5

    Measured: 1 cycle (Cohort 1 and 4 each cycle is 14 days; Cohort 2 and 3 each cycle is 21 days)

  3. Incidence of chemotherapy dose interruption, dose modification, dose discontinuation

    Measured: 1 cycle (Cohort 1 and 4 each cycle is 14 days; Cohort 2 and 3 each cycle is 21 days)

  4. Change in Troponin level

    • Change in troponin levels after administration of chemotherapy, in those treated with and without azeliragon.

    Measured: 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]

Secondary outcomes (6)

  1. Pharmacokinetic (PK) assessment: Cmax

    Maximum observed serum concentration

    Measured: 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

  2. Pharmacokinetic (PK) assessment: tmax

    Time of maximum observed serum concentration

    Measured: 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

  3. Pharmacokinetic (PK) assessment: AUC0-last

    Area under the serum concentration-time curve from time zero to the last quantifiable timepoint

    Measured: 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

  4. Pharmacokinetic (PK) assessment: AUC0-INF

    Area under the serum concentration-time curve from time zero extrapolated to infinity

    Measured: 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

  5. Pharmacokinetic (PK) assessment: AUC0-tau

    Area under the serum concentration-time curve from time zero to the end of the dosing interval

    Measured: 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

  6. Pharmacokinetic (PK) assessment: t1/2

    Terminal elimination half-life

    Measured: 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]

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Feb 2022
  2. Study start6 Jun 2023
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05256745
Sponsor's protocol ID
STUDY00003782
Acronym
RAGE
Status last verified
Dec 2025
First submitted
3 Jan 2022
Last updated
24 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TTP488, ddAC/ddT and TC in people with Cancer Related Cognitive Decline and Non-metastatic Breast Cancer, run by Georgetown University at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Lana Kheir (202-687-9016, lk814@georgetown.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of unacceptable toxicity (time frame: 1 cycle (Cohort 1 and 4 each cycle is 14 days; Cohort 2 and 3 each cycle is 21 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05256745.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2025.

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