Effect of Azeliragon Combined With Stereotactic Radiation Therapy in Patients With Brain Metastases

Trial Title: Effect of Azeliragon Combined With Stereotactic Radiation Therapy in Patients With Brain Metastases

NCT ID: NCT05789589

Condition: Cancer
Metastasis
Metastatic Cancer
Brain Metastases
Brain Metastases, Adult

Conditions: Official terms:
Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Dexamethasone
Methylprednisolone

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Azeliragon
Description: 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)
Arm group label: Azeliragon and Stereotactic Radiosurgery (SRS)

Other name: TTP488

Other name: PF-04494700

Intervention type: Radiation
Intervention name: Stereotactic radiosurgery
Description: Patients will undergo standard of care SRS as per the treating facility's policies.
Arm group label: Azeliragon and Stereotactic Radiosurgery (SRS)

Intervention type: Drug
Intervention name: Corticosteroid
Description: 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).
Arm group label: Azeliragon and Stereotactic Radiosurgery (SRS)

Other name: dexamethasone

Other name: methylprednisolone

Summary: To determine the safety and efficacy of using the drug azeliragon combined with stereotactic radiosurgery. Specifically, to determine if this combination will lead to improved response in the brain (tumor shrinking in size) and overall tumor control (how long tumor remains controlled).

Criteria for eligibility:
Criteria:
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) 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Miami Cancer Institute at Baptist Health, Inc.

Address:
City: Miami
Zip: 33176
Country: United States

Status: Recruiting

Contact:
Last name: Minesh Mehta, M.D.

Phone: 786-596-2000
Email: mineshm@baptisthealth.net

Contact backup:
Last name: Antoinette M Pimentel

Phone: (786) 596-2000
Email: antoinette.pimentel@baptisthealth.net

Investigator:
Last name: Minesh Mehta, M.D.
Email: Principal Investigator

Investigator:
Last name: Yazmin Odia, M.D.
Email: Principal Investigator

Start date: November 17, 2023

Completion date: August 2027

Lead sponsor:
Agency: Baptist Health South Florida
Agency class: Other

Collaborator:
Agency: Miami Cancer Institute
Agency class: Other

Collaborator:
Agency: Cantex Pharmaceuticals Inc.
Agency class: Other

Source: Baptist Health South Florida

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05789589
http://cancer.baptisthealth.net/