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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05789589




Registration number
NCT05789589
Ethics application status
Date submitted
16/03/2023
Date registered
29/03/2023

Titles & IDs
Public title
Effect of Azeliragon Combined With Stereotactic Radiation Therapy in Patients With Brain Metastases
Scientific title
A Phase I/II Study to Assess Safety and Preliminary Evidence of a Therapeutic Effect of Azeliragon Combined With Stereotactic Radiation Therapy in Patients With Brain Metastases
Secondary ID [1] 0 0
2022-KOT-002
Universal Trial Number (UTN)
Trial acronym
ADORATION
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Metastasis 0 0
Metastatic Cancer 0 0
Brain Metastases 0 0
Brain Metastases, Adult 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Azeliragon
Treatment: Other - Stereotactic radiosurgery
Treatment: Drugs - Corticosteroid

Experimental: Azeliragon and Stereotactic Radiosurgery (SRS) - In the Phase 1 portion of the study, three treatment regimens will be systematically evaluated:

1. Azeliragon + SRS + loading corticosteroid dose (LD) + corticosteroid taper (CT)
2. Azeliragon + SRS + loading corticosteroid dose (LD)
3. Azeliragon + SRS

The starting cohort will receive Regimen #2, and depending on the tolerability, participants will be allocated to subsequent cohorts as follows: if Regimen #2 is not well tolerated, participants will be allocated to Regimen #1; if #2 is well tolerated, participants will be allocated to Regimen #3.

Once a Regimen has been identified as safe and tolerable, it will be used for the Phase 2 portion of the study.


Treatment: Drugs: Azeliragon
Dosing will begin on Day 0 with the loading dose and continue daily through Day 7. Starting on Day 8, dosing will resume with the continuous dose until disease progression or 8 weeks. If there is evidence of antitumor effect at 8 weeks, dosing may continue for up 2 two years.

All doses are taken orally. There are three levels of dosing, including a starting dose and two lower levels of dosing. Participants will start with the starting dose, and in the event of the dose limiting toxicities, the dose will be reduced as described below.

Starting Dose Level: 30 mg twice daily (Loading Dose) or 20 mg once daily (Continuous Dose) Dose Level -1: 15 mg twice daily (Loading Dose) or 10 mg once daily (Continuous Dose) Dose Level -2: 15 mg once daily (Loading Dose) or 5 mg once daily (Continuous Dose)

Treatment: Other: Stereotactic radiosurgery
Patients will undergo standard of care SRS as per the treating facility's policies.

Treatment: Drugs: Corticosteroid
Two corticosteroid regimens are used depending on the study cohort. Cohorts 1 and 2 will receive the loading dose (LD). Only Cohort 1 will receive the corticosteroid taper (CT).

LD: Oral (8 mg) or IV bolus dose (10 mg) of dexamethasone or 40 to 80 mg of methylprednisolone on the day of SRS CT: Oral 2-4 mg of dexamethasone twice daily for 5 days and then 2-4 mg daily for 5 days at the discretion of the treating physician (concurrent use of a proton pump inhibitor or H2 receptor antagonists are encouraged during the CT).
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Total Dose-Limiting Toxicities (DLTs)
Timepoint [1] 0 0
4 weeks
Secondary outcome [1] 0 0
CNS treatment-related adverse events
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Early brain metastases response rate
Timepoint [2] 0 0
8 weeks
Secondary outcome [3] 0 0
Intracranial objective response rate
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
Intracranial objective response rate
Timepoint [4] 0 0
12 months
Secondary outcome [5] 0 0
Lesion-specific local tumor control rate
Timepoint [5] 0 0
6 months
Secondary outcome [6] 0 0
Lesion-specific local tumor control rate
Timepoint [6] 0 0
12 months
Secondary outcome [7] 0 0
Neurocognitive outcomes battery
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Change in patient-reported outcomes (PROs)
Timepoint [8] 0 0
Baseline to 24 months
Secondary outcome [9] 0 0
Change in quality of life (QOL) using EORTC QLQ-C30
Timepoint [9] 0 0
Baseline to 24 months
Secondary outcome [10] 0 0
Change in QOL using EORTC QLQ-BN20
Timepoint [10] 0 0
Baseline to 24 months

Eligibility
Key inclusion criteria
1. Patient must have histologically or cytologically confirmed diagnosis of cancer within the past 5 years. If original histologic proof of malignancy is > 5 years, then biological [such as presence of tumor markers, circulating tumor (ctDNA), etc.], or pathological (i.e., more recent) confirmation is required (e.g., from a systemic metastasis or brain metastasis)
2. Age = 18
3. Karnofsky performance status = 50 or Eastern Cooperative Oncology Group (ECOG) = 3
4. Brain metastasis with a maximum tumor diameter of the largest lesion = 2 cm
5. Patients must have discontinued corticosteroids at least 5 days prior to SRS. (Note: This does not apply to corticosteroids administered as part of this protocol.)
6. Patients must not be pregnant (positive pregnancy test) or breast feeding. Effective contraception (men and women) must be used in patients of child-bearing potential during radiotherapy and for 6 months after.
7. Patients who have received prior SRS are eligible, provided that there are new non-irradiated brain lesions and that the patient is = 2 months post prior cranial radiation therapy
8. Patient has adequate biological parameters as demonstrated by the following blood counts at Screening (obtained = 14 days prior to enrollment):

* Absolute neutrophil count (ANC) = 1.0 × 10^9/L
* Platelet count = 75,000/mm^3 (75 × 10^9/L)
* Hemoglobin (Hgb) = 9 g/dL without transfusion or growth factor support
9. Absolute neutrophil count (ANC) = 1.0 × 10^9/L; Platelet count = 75,000/mm^3 (75 × 10^9/L); Hemoglobin (Hgb) = 9 g/dL without transfusion or growth factor support
10. Patient has the following blood chemistry levels at Screening (obtained = 14 days prior to enrollment):

* Aspartate aminotransferase (AST; SGOT), alanine transaminase (ALT; SGPT) = 2.5 × upper limit of normal range (ULN). Total bilirubin = 1.5 × ULN.
* Estimated creatinine clearance of > 60 mL/min (per Cockcroft-Gault formula)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients with leptomeningeal disease
2. Patients unable to undergo magnetic resonance imaging (MRI)
3. Patients receiving Cytochrome P450 (CYP) 2C8 inhibitors as indicated in the protocol
4. Patients with a gastrointestinal condition that could interfere with swallowing or absorption.
5. Females of childbearing potential who are sexually active or males with female partners of childbearing potential, where either the female or the male is unwilling to use a highly effective method of contraception during the trial and for 6 months after the last administration of azeliragon.
6. Patients with concurrent participation in another interventional clinical trial or use of another investigational agent within 7 days of starting azeliragon. Patients who are participating in non-interventional clinical trials (e.g., QOL, imaging, observational, follow-up studies, etc.) are eligible, regardless of the timing of participation.
7. Any patient that in the opinion of the principal investigator is not an appropriate candidate for this trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/11/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/08/2027
Actual
Sample size
Target
46
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida

Funding & Sponsors
Primary sponsor type
Other
Name
Baptist Health South Florida
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Miami Cancer Institute
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Cantex Pharmaceuticals Inc.
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Minesh Mehta, M.D.
Address 0 0
Miami Cancer Institute at Baptist Health, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Minesh Mehta, M.D.
Address 0 0
Country 0 0
Phone 0 0
(786) 596-2000
Fax 0 0
Email 0 0
mineshm@baptisthealth.net
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05789589