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RAGE Inhibition to Decrease Cardiotoxicity in Women With Early Breast Cancer

ConditionsCancer Related Cognitive DeclineNon-metastatic Breast Cancer
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexFemale
Age18+
SponsorGeorgetown University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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).

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • TTP488

    Drug

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

  • ddAC/ddT

    Drug

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

  • TC

    Drug

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

  • TCHP

    Drug

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

  • Chemotherapy regimen that includes ddAC

    Drug

    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

Treatment groups

48 Participants
are divided into 4 treatment groups
Group A: Cohort 1: TTP488 (Azeliragon) co-administered with dose dense paclitaxel (ddAC/ddT)Experimental treatment 2 interventions
Group B: Cohort 2: TTP488 (Azeliragon) co-administered with TCExperimental treatment 2 interventions
Group C: Cohort 3: TTP488 (Azeliragon) co-administered with TCHPExperimental treatment 2 interventions
Group D: Cohort 4: TTP488 (Azeliragon) co-administered with chemotherapy regimen that includes ddACExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

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

Time frame
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

Time frame
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

Time frame
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.

Time frame
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

1

Pharmacokinetic (PK) assessment: Cmax

Maximum observed serum concentration

Time frame
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

Time frame
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

Time frame
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

Time frame
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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Georgetown University

Lead sponsor

Source ClinicalTrials.gov
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