A Phase I De-Escalation Study of Dexamethasone With Azeliragon for Management of Post-Resection Cerebral Edema in Patients With Glioblastoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 21
- 主要终点
- Lack of feasibility
研究概览
简要总结
This phase I trial tests the safety, side effects, and best dose of dexamethasone when given with azeliragon in managing cerebral edema after surgery (post-resection) in patients with glioblastoma. Cerebral edema is a pathological increase in the water mass contained within the brain interstitial space. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Azeliragon is an oral RAGE inhibitor. Blocking the RAGE pathway at the time of surgery (peri-operatively) may decrease cerebral edema. Giving dexamethasone with azeliragon may help control post-operative cerebral edema in decreasing doses of concurrently administered dexamethasone.
详细描述
PRIMARY OBJECTIVES:
I. Determine the lowest dose of dexamethasone that needs to be co-administered with azeliragon for treatment of post-resection cerebral edema in patients with glioblastoma.
II. Assess the safety of administering azeliragon peri-operatively to patients with glioblastoma.
SECONDARY OBJECTIVES:
I. Describe post-operative changes in levels of cytokines and chemokines in brain interstitium and peripheral blood in study participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Documented informed consent of the participant and/or legally authorized representative
- •Age: >= 18 years
- •Karnofsky performance status of >= 60%
- •Histologically confirmed glioblastoma or radiographic findings consistent with a high grade glioma in patients undergoing surgery for initial diagnosis
- •If midline shift is present on the pre-op brain MRI, it must be less than 10 mm
- •The patient is planning to undergo a standard of care craniotomy, and the neurosurgeon anticipates being able to perform a gross total resection of tumor
- •If a patient is taking more than 3 mg twice daily (bid) of dexamethasone at the time of signing the consent form, it is anticipated by the neurosurgeon that the participant will be able to decrease their dose of dexamethasone to 3 mg bid by 6 days before the surgery
- •Note: If the patient is not able to decrease their dose of dexamethasone to 3 mg BID 6 days before surgery, then the patient will not be allowed to participate in the study
- •The patient is not planning to participate in another clinical trial during the study period
- •The patient has recovered from any acute toxic effects (except alopecia) to =< grade 1 of prior anti-cancer therapy
- •Absolute neutrophil count (ANC) >= 1,000/mm^3
- •Platelets >= 100,000/mm^3
- •Total bilirubin =< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)
- •Aspartate aminotransferase (AST) =< 1.5 x ULN
- •Alanine aminotransferase (ALT) =< 1.5 x ULN
- •Creatinine clearance of >= 60 mL/min by the Cockcroft-Gault formula
- •International normalized ratio (INR) OR prothrombin (PT) =< 1.5 x ULN
- •Activated partial thromboplastin time (aPTT) =< 1.5 x ULN
- •Corrected QT (QTc) =< 480 ms
- •Note: To be performed within 28 days prior to day 1 of protocol therapy
- •People of childbearing potential: negative urine or serum pregnancy test
- •Agreement by people of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
- •Childbearing potential defined as not being surgically sterilized (regardless of gender) or not being free from menses for > 1 year (people with uteri only)
排除标准
- •Less than 6 weeks since taking a nitrosourea-containing chemotherapy regimen; less than 4 weeks since completing a non-nitrosourea-containing cytotoxic chemotherapy regimen (except temozolomide: only patients with an interval of less than 23 days from the last dose administered when treated with the temozolomide regimen of daily for 5 days, repeated every 28 days are excluded); less than 2 weeks from taking the last dose of a targeted agent; less than 4 weeks from the last dose of bevacizumab
- •Less than 3 months since focal brain radiation unless recurrent disease has been confirmed surgically or the area of recurrent tumor is outside of the radiation field
- •The patient is taking a medication that is a strong CYP3A4 inducers/ inhibitors within 14 days prior to day -6 of protocol therapy
- •The patient is unwilling to stop taking herbal medications prior to the start of study treatment
- •The patient is taking a hepatic enzyme-inducing anticonvulsant within 14 days prior to day -6 of protocol therapy
- •Clinically significant uncontrolled illness
- •Active infection requiring antibiotics
- •Human immunodeficiency virus (HIV)-positive
- •Undergoing treatment for another cancer
- •Issues with tolerating oral medication (e.g. inability to swallow pills, malabsorption issues, ongoing nausea or vomiting)
- •Chronic or active viral infection of the central nervous system (CNS)
- •Pregnant or breastfeeding
- •Coagulopathy or bleeding disorder
- •Inability to undergo a brain MRI
- •Inability to tolerate dexamethasone
- •Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
研究组 & 干预措施
Arm I (azeliragon, dexamethasone)
Patients receive azeliragon PO and dexamethasone PO or IV throughout the study. Patients also undergo collection of cavity fluid and blood samples, CT scan, and brain MRI with or without contrast throughout the study.
干预措施: Azeliragon (Drug)
Arm I (azeliragon, dexamethasone)
Patients receive azeliragon PO and dexamethasone PO or IV throughout the study. Patients also undergo collection of cavity fluid and blood samples, CT scan, and brain MRI with or without contrast throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm I (azeliragon, dexamethasone)
Patients receive azeliragon PO and dexamethasone PO or IV throughout the study. Patients also undergo collection of cavity fluid and blood samples, CT scan, and brain MRI with or without contrast throughout the study.
干预措施: Computed Tomography (Procedure)
Arm I (azeliragon, dexamethasone)
Patients receive azeliragon PO and dexamethasone PO or IV throughout the study. Patients also undergo collection of cavity fluid and blood samples, CT scan, and brain MRI with or without contrast throughout the study.
干预措施: Dexamethasone (Drug)
Arm I (azeliragon, dexamethasone)
Patients receive azeliragon PO and dexamethasone PO or IV throughout the study. Patients also undergo collection of cavity fluid and blood samples, CT scan, and brain MRI with or without contrast throughout the study.
干预措施: Magnetic Resonance Imaging of the Brain with and without Contrast (Procedure)
Arm II (dexamethasone)
Patients receive dexamethasone PO or IV throughout the study. Patients also undergo collection of cavity fluid and blood samples, CT scan, and brain MRI with or without contrast throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm II (dexamethasone)
Patients receive dexamethasone PO or IV throughout the study. Patients also undergo collection of cavity fluid and blood samples, CT scan, and brain MRI with or without contrast throughout the study.
干预措施: Computed Tomography (Procedure)
Arm II (dexamethasone)
Patients receive dexamethasone PO or IV throughout the study. Patients also undergo collection of cavity fluid and blood samples, CT scan, and brain MRI with or without contrast throughout the study.
干预措施: Dexamethasone (Drug)
Arm II (dexamethasone)
Patients receive dexamethasone PO or IV throughout the study. Patients also undergo collection of cavity fluid and blood samples, CT scan, and brain MRI with or without contrast throughout the study.
干预措施: Magnetic Resonance Imaging of the Brain with and without Contrast (Procedure)
结局指标
主要结局
Lack of feasibility
时间窗: Up to 8 days after surgery
Defined by exceeding the planned total dose of dexamethasone (per dose level) during post-operative days 1 to 8 by approximately 50%.
Incidence of adverse events
时间窗: Up to 30 days post-last dose of protocol therapy
Azeliragon related adverse events and dose limiting toxicity rate assessed per Common Terminology Criteria for Adverse Events version 5.0.
次要结局
- Cytokines/chemokines(Up to 3 days after surgery)
- Volume of cerebral edema(Up to 8 days after surgery)
- Azeliragon concentrations(Up to 8 days after surgery)