Solid Tumor, High-grade Glioma, Leptomeningeal Metastasis
Conditions
Brief summary
Single institution study to assess the safety of concurrent Azeliragon with craniospinal irradiation (CSI) in patients with leptomeningeal metastasis from solid tumor malignancies and high-grade gliomas.
Interventions
DRUGAzeliragon
Azeliragon is orally administered. Patients start Azeliragon 7 days before CSI and take their last dose 7 days post-CSI. The first 6 patients will start at Dose Level 1 \[DL1\] (Loading dose for 7 days: 30 mg twice daily; Concurrent/adjuvant dose: 20 mg once daily). If 1 or fewer of 6 patients develop dose-limiting toxicity (DLT) then the recommended dose will be DL1. If at least 2 of 6 develops a DLT, then an additional 6 patients will be enrolled at Dose Level -1 \[DL-1\] (Loading dose for 7 days: 15mg twice daily; Concurrent/adjuvant dose: 10mg once daily). If 1 or fewer out of 6 patients at DL-1 develop DLT, then the recommended dose will be DL-1. If at least 2 of 6 at DL-1 develops a DLT, then an additional 6 patients will be enrolled at Dose Level -2 \[DL-2\] (Loading dose for 7 days: 15mg twice daily; Concurrent/adjuvant dose: 5mg once daily). At the recommended dose, an additional 14 patients will be enrolled for the Dose Expansion portion.
PROCEDURECSI
Patients will receive CSI.
Sponsors
NYU Langone Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with solid tumor malignancy or high grade glioma with leptomeningeal metastasis established radiographically and/or through cerebrospinal fluid (CSF) cytology * Patients who are candidates for radiation therapy for the treatment of leptomeningeal metastasis * Patients with Karnofsky Performance Status of 60 or greater. * Male or non-pregnant and non-lactating female and ≥ 18 years of age. * Patients with absolute neutrophil count (ANC) ≥ 1.0 × 109/L, platelet count ≥ 75,000/mm3 (75 × 109/L), and hemoglobin (Hgb) ≥ 8 g/dL. Transfusion or growth factor support is allowed. * Patients with aspartate aminotransferase (AST) \[serum glutamic-oxaloacetic transaminase(SGOT)\], alanine aminotransferase (ALT) \[serum glutamic-pyruvic transaminase (SGPT)\] ≤ 2.5 × upper limit of normal range (ULN), unless liver metastases are present, then ≤ 5 x ULN is acceptable, total bilirubin ≤ 1.5 × ULN, and estimated creatinine clearance of \> 30 mL/min (per Cockroft-Gault formula). * Patient has been informed about the nature of the study, and has agreed to participate in the study, and signed the Informed Consent Form (ICF) prior to participation in any study-related activities.
Exclusion criteria
* Patient has a life expectancy, per investigator assessment, of less than 2 months. * Patients unable to complete the English quality of life questionnaires * Patient with extensive systemic disease and who declined standard systemic treatment options * Patient who is unable to undergo magnetic resonance imaging (MRI) brain and spine with gadolinium contrast * Previous radiotherapy to the intended treatment site that precludes developing a treatment plan that respects normal tissue tolerance * Active, uncontrolled bacterial, or fungal infection(s) requiring systemic therapy. * Patient has a concomitant serious medical or psychiatric illness that, in the opinion of the investigator, could compromise the patient's safety or the study data integrity. * Patient is unwilling or unable to comply with study procedures, including, but not limited to self-administration of oral medication. * Patients with a gastrointestinal condition that could interfere with swallowing or absorption. * 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 study drug. * Pregnant or lactating women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients with Dose-Limiting Toxicities (DLTs) at Dose Level 1 | Up to Week 4 | DLTs assess using Common Terminology Criteria for Adverse Events (CTCAE) v 5.0. |
| Number of Patients with DLTs at Dose Level -1 | Up to Week 4 | DLTs assess using CTCAE v 5.0. |
| Number of Patients with DLTs at Dose Level -2 | Up to Week 4 | DLTs assess using CTCAE v 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Central nervous system (CNS) progression-free survival (PFS) | Up to Month 13 (12 Months Post-Protocol Therapy) | CNS PFS is defined as time from randomization until CNS progression or death, whichever occurs first. |
| Overall Survival (OS) | Up to Month 13 (12 Months Post-Protocol Therapy) | OS is defined as time from randomization until death. |
Countries
United States
Contacts
Primary ContactJonathan Yang, MD, PhD
Backup ContactCancer Trials Office
Outcome results
None listed