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
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 发起方
- 入组人数
- 46
- 试验地点
- 2
- 主要终点
- Total Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
- •Karnofsky performance status ≥ 50 or Eastern Cooperative Oncology Group (ECOG) ≤ 3
- •Brain metastasis with a maximum tumor diameter of the largest lesion ≤ 2 cm
- •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.)
- •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.
- •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
- •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
- •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
- •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)
排除标准
- •Patients with leptomeningeal disease
- •Patients unable to undergo magnetic resonance imaging (MRI)
- •Patients receiving Cytochrome P450 (CYP) 2C8 inhibitors as indicated in the protocol
- •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 azeliragon.
- •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.
- •Any patient that in the opinion of the principal investigator is not an appropriate candidate for this trial
研究组 & 干预措施
Azeliragon and Stereotactic Radiosurgery (SRS)
In the Phase 1 portion of the study, three treatment regimens will be systematically evaluated:
- Azeliragon + SRS + loading corticosteroid dose (LD) + corticosteroid taper (CT)
- Azeliragon + SRS + loading corticosteroid dose (LD)
- 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.
干预措施: Stereotactic radiosurgery (Radiation)
Azeliragon and Stereotactic Radiosurgery (SRS)
In the Phase 1 portion of the study, three treatment regimens will be systematically evaluated:
- Azeliragon + SRS + loading corticosteroid dose (LD) + corticosteroid taper (CT)
- Azeliragon + SRS + loading corticosteroid dose (LD)
- 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.
干预措施: Corticosteroid (Drug)
Azeliragon and Stereotactic Radiosurgery (SRS)
In the Phase 1 portion of the study, three treatment regimens will be systematically evaluated:
- Azeliragon + SRS + loading corticosteroid dose (LD) + corticosteroid taper (CT)
- Azeliragon + SRS + loading corticosteroid dose (LD)
- 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.
干预措施: Azeliragon (Drug)
结局指标
主要结局
Total Dose-Limiting Toxicities (DLTs)
时间窗: 4 weeks
A DLT of the azeliragon and corticosteroid regimen is defined as any central nervous system (CNS)-specific Grade ≥ 2 toxicity requiring corticosteroid treatment or any Grade ≥ 3 events that are not clearly due to the underlying disease or extraneous causes. DLTs will be considered up to four weeks after SRS.
次要结局
- CNS treatment-related adverse events(24 months)
- Early brain metastases response rate(8 weeks)
- Intracranial objective response rate(12 months)
- Lesion-specific local tumor control rate(12 months)
- Neurocognitive outcomes battery(24 months)
- Change in patient-reported outcomes (PROs)(Baseline to 24 months)
- Change in quality of life (QOL) using EORTC QLQ-C30(Baseline to 24 months)
- Change in QOL using EORTC QLQ-BN20(Baseline to 24 months)
- Intracranial objective response rate(6 months)
- Lesion-specific local tumor control rate(6 months)