A Phase 3 Multicenter Study of Gleolan (Aminolevulinic Acid Hydrochloride) to Enhance Visualization of Tumor in Patients With Newly Diagnosed or Recurrent Meningiomas
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 108
- 试验地点
- 23
- 主要终点
- The proportion of participants who have at least one indeterminate tissue or unexpected fluorescent End of Surgery (EOS) tissue where Gleolan-induced PpIX fluorescence status is consistent with histology.
研究概览
简要总结
This Phase 3 open-label single-arm study is designed to investigate the safety, diagnostic performance, and clinical usefulness of Gleolan for the real time detection and visualization of meningiomas during tumor resection surgery. The study is planned to run for 15 months with individual study participation lasting for approximately 2 months.
详细描述
This Phase 3 open-label single-arm study is designed to investigate the safety, diagnostic performance, and clinical usefulness of the imaging agent Gleolan™ (Aminolevulinic Acid Hydrochloride, ALA HCl, ALA, 5-ALA), an orally administered imaging agent for the real time detection and visualization of meningiomas during tumor resection surgery. ALA is a prodrug that is metabolized intracellularly to form the fluorescent molecule Protoporphyrin IX (PpIX). The exogenous application of ALA leads to a highly selective accumulation of PpIX in tumor cells. Following excitation with blue light (BL) (λ = 375 - 440 nm), the PpIX, which has accumulated selectively in tumor tissue, emits a red-violet light. This phenomenon allows for the real-time visualization of tumor tissue during resection surgery.
Patients about to undergo resection for suspected meningioma [World Health Organization (WHO) Grade I, II, III] will be screened and informed consent will be obtained prior to surgery and prior to study participation. Eligible study participants will receive an oral solution of Gleolan (20 mg/kg body weight) 3 hours, (target range 2-4 hours) prior to anesthesia, and then undergo surgery for meningioma resection. During the surgery, the surgeon will use a microscope equipped with WL and BL for visualization of Gleolan-induced PpIX fluorescence for the selection of protocol-driven tissue locations and to assess fluorescence status.
Study participants will be evaluated within 48 hours post procedure, 2 weeks post procedure, and 6 weeks post procedure for study safety assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 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
- •A pre-operative MRI within ≤ 90 days of study enrollment documenting a suspected meningioma or suspected recurrence of a meningioma for which a meningioma resection is indicated and has been planned.
- •Adult age ≥ 18 years.
- •Patient must have normal organ and bone marrow function and be appropriate surgical candidates per site SOC.
- •Patient must have recording of each parameter as defined below:
- •Bilirubin Below upper limit of normal AST (SGOT) < 2.5 X institutional upper limit of normal ALT (SGPT) < 2.5 X institutional upper limit of normal Creatinine Below upper limit of normal OR Creatinine clearance >60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal
- •The patient must demonstrate the ability to understand the informed consent document and the willingness and ability to sign a written informed consent document. The study consent documents will be prepared in English and German and Spanish. Translation for non-English, non-German, or non-Spanish speaking participants will be provided as appropriate by institution, as required.
- •WOCBP and men participating must agree to use highly effective forms of contraception, and men must also agree not to donate sperm for the duration of treatment, and for at least 42 days after the one time use of the study drug.
排除标准
- •History of allergic reactions attributed to compounds of similar chemical/biologic composition to Gleolan.
- •Known or documented personal or family history of porphyria.
- •Uncontrolled concurrent illness, including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia or psychiatric illness.
- •Patient has had a meningioma resection or radiation treatment within 90 days of informed consent.
- •Social or medical situations that would limit compliance with study requirements (e.g. ability to travel for follow-up or inability to obtain appropriate pre-op MRI (e.g. cardiac pacemaker).
- •Women who are pregnant or plan to become pregnant during study participation.
- •Prior history of gastrointestinal perforation, diverticulitis, and or/peptic ulcer disease within 90 days of informed consent.
- •Simultaneous participation in another clinical study or participation in another clinical study in the 30 days directly preceding treatment or within 5 plasma half-life of the preceding study drug, whatever is longer.
- •Simultaneous use of other potentially phototoxic substances (St. John's wort, griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, quinolones and tetracyclines), and topical preparations containing ALA for 24 hours during the perioperative period (see MOPS for detailed list).
- •Unwillingness by patient to sign consent or return for subsequent visits following surgery.
- •Any condition that in the opinion of the Investigator would exclude the patient as a viable candidate for this study.
研究组 & 干预措施
Single Arm
Open-label, intra-subject control
干预措施: Gleolan (Drug)
结局指标
主要结局
The proportion of participants who have at least one indeterminate tissue or unexpected fluorescent End of Surgery (EOS) tissue where Gleolan-induced PpIX fluorescence status is consistent with histology.
时间窗: Surgery (Day 1)
Per Protocol Population
The Percentage of Participants Who Had at Least 1 Indeterminate Tissue or Unexpected Fluorescent End of Surgery (EOS) Tissue Where Gleolan-induced PpIX Fluorescence Status is Consistent With Histology (i.e., True Positive or True Negative for Meningioma).
时间窗: Surgery (Day 1)
Responders are defined as the percentage of participants among all participants receiving Gleolan (the Intent to Image Population) who had at least one indeterminate tissue or unexpected fluorescent end of surgery (EOS) tissue where Gleolan-induced PpIX fluorescence status was consistent with central laboratory histology. For a participant to be considered a success, only biopsies considered 'non-obvious' for tumor status by an external panel of neurosurgeons who reviewed videos and images were eligible to be assessed in the numerator. A two-sided 95% confidence interval was calculated using the Wilson (score) method. The lower bound of the confidence interval was tested against a null hypothesis value of 30%. A modified worst-case imputation was used for missing data.
次要结局
- Positive Predicted Value (PPV) of Gleolan-induced PpIX fluorescence of the single bulk tumor tissue obtained from each study participant(Surgery (Day 1))
- The concordance between the Surgeon and Adjudication Panel assessment of white light (WL) visualization visualization to identify tissue as likely or unlikely to be meningioma among indeterminate tissues.(Surgery (Day 1))
- Diagnostic accuracy of Gleolan-induced PpIX fluorescence among indeterminate tissue and unexpected fluorescent EOS tissue locations is at least 20% greater than the diagnostic accuracy of the surgeons' assessment.(Surgery (Day 1))
- Diagnostic performance of Gleolan-induced PpIX fluorescence will be computed for indeterminate tissue biopsies, unexpected fluorescent EOS tissue biopsies.(Surgery (Day 1))
- The concordance between the Surgeon and Adjudication Panel assessment of blue light (BL) visualization to identify fluorescence status of indeterminate tissues.(Surgery (Day 1))
- Positive Predicted Value (PPV) of Gleolan-induced PpIX Fluorescence Status of Biopsied Tissue Locations at the Margin of the Tumor [Indeterminate Tissues and Unexpected Fluorescent EOS Tissues (Combined)].(Surgery (Day 1))
- Negative Predicted Value (NPV) of Gleolan-induced PpIX Fluorescence Status of Biopsied Tissue Locations at the Margin of the Tumor [Indeterminate Tissues].(Surgery (Day 1))
- Positive Predictive Value of Single Bulk Tumor Sample Obtained From Each Participant.(Surgery (Day 1))