A Phase I Study of Convection-Enhanced Delivery of Liposomal-Irinotecan Using Real-Time Imaging With Gadolinium In Patients With Recurrent High Grade Glioma

University of California, San Francisco1 个研究点分布在 1 个国家目标入组 18 人开始时间: 2014年10月23日最近更新: 2023年6月29日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: University of California, San Francisco
入组人数: 18
试验地点: 1
主要终点: Maximum tolerated dose

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a single center, dose-toleration study designed to investigate and determine the maximum tolerated dose of nanoliposomal irinotecan in adults with recurrent high-grade glioma when administered directly into the tumor using a process called convection-enhanced delivery (CED).

详细描述

PRIMARY OBJECTIVE:

I. To determine the safety and tolerability of liposomal-irinotecan with gadolinium given by intra tumoral real-time convection enhanced delivery in patients with recurrent high grade glioma (HGG).

SECONDARY OBJECTIVES:

I. To optimize the magnetic resonance image-guided intracranial injection procedure in patients with recurrent HGG by correlating the observed distribution of gadolinium to pre-treatment modeling of the drug distribution utilizing predictive imaging software.

EXPLORATORY OBJECTIVES:

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Single Group
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

•Patients with radiographically proven recurrent, intracranial high grade glioma will be eligible for this protocol. Patients must have evidence of tumor progression as determined by the Revised Assessment in Neuro-Oncology RANO criteria following standard therapy.
•High grade glioma includes glioblastoma multiforme (GBM), Gliosarcoma (GS), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), anaplastic mixed oligoastrocytoma (AMO), or malignant astrocytoma not otherwise specified. (NOS)
•Magnetic resonance imaging (MRI) must be performed within 21 days prior to enrollment, and patients who are receiving steroids must be stable or decreasing for at least 5 days prior to imaging. If the steroid dose is increased between the date of imaging and enrollment, a new baseline MRI is required.
•Patients must have completed only 1 prior course of radiation therapy and must have experienced an interval of greater than 12 weeks from the completion of radiation therapy to study entry.
•Patients will be eligible if the original histology was low-grade glioma and a subsequent histological diagnosis of a high grade glioma is made.
•There is no limit as to the number of prior treatments but patients must have radiographic evidence of progressive disease
•Recurrent tumor must be a solid, single, supratentorial, contrast-enhancing HGG which have a tumor diameter no larger than 4cm or volume of 34cm3
•All patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
•a. Patients must be> 18 years old, and with a life expectancy > 8 weeks
•Patients with Karnofsky performance status of >=
•At the time of registration: Patients must have recovered from the toxic effects of prior therapy: > 10 days from any noncytotoxic investigational agent, >28 days from prior cytotoxic therapy or Avastin, >14 days from vincristine, >42 days from nitrosoureas, >21 days from procarbazine administration, and >7 days for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the Study Chair.
•Requirements for organ and marrow function as follows:
•Adequate bone marrow function:
•leukocytes > 3,000/microliter (mcL)
•absolute neutrophil count > 1,500/mcL
•platelets > 100,000/mcL
•Adequate hepatic function:
•total bilirubin within normal institutional limits
•aspartate aminotransferase (AST) < 2.5 X institutional upper limit of normal
•alanine aminotransferase (ALT) < 2.5 X institutional upper limit of normal
•Adequate renal function:
•creatinine within normal institutional limits OR
•creatinine clearance > 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal.
•Adequate coagulation function
•International Normalized Ratio (INR) < 2.0
•partial thromboplastin time (PTT) <= institution's upper limit of normal, unless receiving therapeutic low molecular weight heparin.
•The effects of nano liposomal irinotecan on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception: hormonal or barrier method of birth control; abstinence, etc. prior to study entry, for the duration of study participation, and for 6 months post drug administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
•Women of childbearing potential must have a negative beta-human chorionic gonadotropin (beta-HCG) pregnancy test documented within 14 days prior to treatment.
•Patients with prior therapy that included interstitial brachytherapy, or Gliadel wafers must have confirmation of true progressive disease rather than radiation necrosis based upon either Positron Emission Tomography (PET) or Thallium scanning, MR spectroscopy or surgical documentation of disease
•Patients must be able to have MRI brain imaging.
•UGT1A1 genotyping will be sent for testing at screening, but results do not have to be known before starting treatment

排除标准

•Patients must not have any significant medical illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy
•Patients with a history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission and off of all therapy for that disease for a minimum of 3 years are ineligible.
•HIV-positive patients on combination antiretroviral therapy are ineligible.
•Contrast-enhancing tumor which crosses the midline.
•Multi-focal disease.
•Nonparenchymal tumor dissemination (e.g., subependymal or leptomeningeal)
•History of hypersensitivity reactions to products containing irinotecan (irinotecan), topotecan or other topoisomerase inhibitors, gadolinium contrast agents or lipid products.
•Ongoing treatment with cytotoxic therapy.
•Patients may not be on an enzyme-inducing anti-epileptic drug (EIAED). If previously on an EIAED, patient must be off for at least 10 days prior to CED infusion.

研究组 & 干预措施

Group 1 - 20 mg

Experimental

Tumor diameter: 1 cm, Tumor volume: ~0.5cm3, Infusion Volume: 2-3 ml, Irinotecan conc.: 20 mg/ml, Infusion time: 6-24 hours, no more than 48