NCT01880749已完成早期 1 期
Exploring the Activity of RAD001 in Vestibular Schwannomas and Meningiomas
适应症
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Proportions of VS and meningiomas after exposure to RAD001
研究概览
简要总结
The primary objective is to estimate the proportions of vestibular schwannomas (VS) and meningiomas after 10 days of exposure to the study drug RAD001 at a dose of 10 mg daily, as determined by immunohistochemistry. This is a "phase 0" PK (pharmacokinetic) and PD (pharmacodynamic) study of RAD001 in patients with Neurofibromatosis Type 2-related and sporadic VS and meningiomas. Enrolled patients will take RAD001 prior to a scheduled VS or meningioma surgery, and blood and tissue samples will be obtained for further analysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Patients must satisfy all of the following eligibility criteria:
- •Karnofsky performance status (KPS) ≥ 60%
- •Absolute neutrophil count ≥ 1,000/mm³ (unsupported)
- •Platelet count ≥ 100,000/mm³ (unsupported)
- •Hemoglobin ≥ 8 g/dl (transfusion support allowed)
- •Creatinine ≤ 1.5 times upper limit of normal (ULN*) OR corrected glomerular filtration rate ≥ 70 ml/min
- •Total bilirubin ≤ 1.5 times ULN*
- •ALT ≤ 2.5 times ULN*
- •Serum albumin ≥ 2 g/dl
- •INR < 1.3 (or < 3 on anticoagulants)
- •Patients taking a cholesterol-lowering agent must be on a single medication and on a stable dose for at least 4 weeks
- •Fasting serum cholesterol ≤ 300 mg/dl OR ≤ 7.75 mmol/l AND fasting triglycerides ≤ 2.5 times ULN*.
- •Fully recovered from acute toxic effects of any prior chemotherapy, biological modifiers or radiotherapy
- •Any neurologic deficits must be stable for ≥ 1 week
- •Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative pregnancy test. The anti-proliferative activity of this experimental drug may be harmful to the developing fetus.
- •Able to provide written informed consent
排除标准
- •Patients with any of the following are ineligible for this research study:
- •Patients with VS or meningiomas deemed very high surgical risk for stroke and/or other complications by the attending surgeon, such as meningiomas with major vascular or dural sinus infiltration.
- •Patients with serious concurrent infection or medical illness, which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety.
- •Symptomatic congestive heart failure or unstable angina pectoris.
- •Uncontrolled diabetes, as defined by fasting serum glucose >1.5 times ULN*.
- •Current active hepatic or biliary disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis (with exception of patients with Gilbert's syndrome and asymptomatic gallstones).
- •History of hepatitis B or C. Note: A detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients. HBV serology, DNA and/or HCV RNA PCR testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection. If no positive medical history for risk factors, serology is not required.
- •Seropositivity or DNA/RNA positivity for hepatitis B or C, with the exception of patients who have received prior Hepatitis B vaccination and are Anti-HBs positive only.
- •Known HIV seropositivity
- •Neurologic deficits that are rapidly progressing: all neurologic signs and symptoms must have been stable for a week prior to first dose
- •Patients who are pregnant or breast-feeding. The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant.
- •Anti-tumor therapy (i.e. chemotherapeutics or investigational agents or immunotherapy) within 4 weeks prior to enrollment
- •Radiation therapy to a study target lesion within 6 months
- •Prior therapy with mTOR inhibitors, including sirolimus, temsirolimus, deforolimus within 6 months prior to enrollment
- •Known hypersensitivity to RAD001 or other rapamycins (sirolimus, temsirolimus, deforolimus)
- •Patients with a concurrent malignancy
- •Patients treatment with systemic steroids or another immunosuppressive agent. Patients with endocrine deficiencies are allowed to receive physiologic or stress doses of steroids if necessary.
- •Patients cannot receive CYP3A4 inhibiting drugs including antibiotics (clarithromycin, erythromycin, troleandomycin), anti-HIV agents (delaviridine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir), antifungals (itraconazole, ketoconazole, fluconazole at doses > 200 mg/day, voriconazole), antidepressants (nefazodone, fluovoxamine), calcium channel blockers (verapamil, diltiazem) oramiodarone
- •Patients should avoid CYP3A4 inhibiting foods including grapefruit and Seville orange juice.
- •Patients cannot receive CYP3A4 inducing anticonvulsants including carbamazepine, felbamate, phenobarbital, phenytoin, primidone and oxcarbazepine, or other CYP3A4 inducers such as St. John's Wort
- •Patients who previously received CYP3A4 inducers or inhibitors must have discontinued these medications within at least 1 week prior to study entry and can re-start them 1 week post-operatively (or earlier if determined to be of clinical benefit, as determined by the treating physician).
- •of institutional norms
研究组 & 干预措施
RAD001
Experimental
RAD001 taken by mouth 10mg daily for 10 days before surgery
干预措施: RAD001 (Drug)
结局指标
主要结局
Proportions of VS and meningiomas after exposure to RAD001
时间窗: 10 days
1) To estimate the proportions of VS and meningiomas with complete inhibition of phospho-S6 after10 days of exposure to RAD001 at a dose of 10 mg daily, as determined by immunohistochemistry. This endpoint was chosen based on prior pharmacodynamic data from a published trial, showing complete inhibition of phospho-S6 in solid tumor tissue of patients treated with RAD001 and our own preliminary data confirming baseline phospho-S6 expression in VS and meningiomas.
次要结局
未报告次要终点
研究者
研究点 (1)
Loading locations...
相似试验
已完成
不适用
Vestibular Evaluation After Vestibular Schwannoma TreatmentDizzinessNCT03670589University Hospital, Grenoble51
Unknown
不适用
Preoperative Vestibular Rehabilitation Effectiveness After Vestibular Schwannoma SurgeryVestibular SchwannomaNCT02275325Central Hospital, Nancy, France50
尚未招募
不适用
Remote Ischemic Preconditioning in Vestibular Schwannoma SurgeryVestibular SchwannomaNCT05567341University Hospital Tuebingen120
已完成
不适用
Use of DTT to Define Facial Nerve Position in Vestibular SchwannomasVestibular SchwannomaNCT04057976King's College Hospital NHS Trust38
终止
2 期
Phase II Study of RAD001 Head and Neck CancerSquamous Cell Carcinoma of the Head and NeckNCT01051791Julie E. Bauman, MD, MPH13