A Study of Ad-RTS-hIL-12 With Veledimex in Subjects With Glioblastoma or Malignant Glioma
This research study involves two investigational drugs, veledimex, an activator ligand (INXN-1001) in combination with an Adenovirus Vector Engineered to Express hIL-12 (INXN-2001). IL-12 is a protein that may improve the body's natural response to disease by enhancing the ability of the immune system to kill tumor cells and may interfere with blood flow to the tumor.
The main purpose of this study is to evaluate the safety and tolerability of a single tumor injection of INXN-2001 given in combination with oral veledimex.
|Glioblastoma Multiforme Anaplastic Oligoastrocytoma||Biological: INXN-2001 Drug: veledimex||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Ad-RTS-hIL-12, an Inducible Adenoviral Vector Engineered to Express hIL-12 in the Presence of the Activator Ligand Veledimex in Subjects With Recurrent or Progressive Glioblastoma or Grade III Malignant Glioma|
- Safety and tolerability of varying doses of intratumoral Ad-RTS-hIL-12 and oral veledimex doses in subjects with recurrent or progressive glioblastoma or Grade III malignant glioma [ Time Frame: 3 years ]Evaluation will be based on the incidence, intensity, and type of Adverse Events (AEs). Clinically significant changes in the subjects' physical examinations, vital signs, and ECG evaluations, and clinical manifestations relevant to abnormal laboratory values will be captured as AEs.
- Veledimex maximum tolerated dose (MTD) when given with varying doses of intratumoral Ad-RTS-hIL-12 [ Time Frame: 3 years ]
- Veledimex pharmacokinetic profile and veledimex concentration ratop betwee the brain tumor and the blood [ Time Frame: 3 years ]Veledimex PK parameters to be determined will include, but are not limited to, the maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), half-life (t1/2), area-under-the-concentration versus time curve (AUC), volume of distribution (Vd), and clearance (CL). Where possible, descriptive statistics of the PK parameters will be provided; individual subject veledimex concentrations, actual sampling times, and PK parameters will be listed.
- Cellular and humoral immune responses elicited by Ad-RTS-hIL-12 and veledimex [ Time Frame: 3 years ]
- Tumor Objective Response Rate (ORR) [ Time Frame: 3 years ]
- Progression-free survival (PFS) [ Time Frame: 3 years ]
- Overall survival (OS) [ Time Frame: 3 years ]
|Study Start Date:||June 2015|
|Estimated Study Completion Date:||December 2019|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: Veledimex in combination with INXN-2001
varying doses of intratumoral INXN-2001 (Ad-RTS-hIL-12) and oral veledimex (activator ligand).
Other Name: Ad-RTS-hIL-12Drug: veledimex
Eligible patients will be stratified to one of two groups, according to clinical indication for tumor resection. Patients who are scheduled for a standard of care craniotomy and tumor resection will receive one dose of veledimex before the resection procedure. Ad-RTS-hIL-12 will be administered by free-hand injection. Patients will continue on oral veledimex for 14 days.
Patients not scheduled for tumor resection will receive Ad-RTS-hIL-12 by stereotactic injection and then will continue on oral veledimex for 14 days.
The study is divided into three periods: the screening period, the treatment period and the follow-up period.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02026271
|United States, California|
|Los Angeles, California, United States, 90048|
|United States, Illinois|
|Chicago, Illinois, United States, 60611|
|University of Chicago||Recruiting|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Brigham & Women's||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Study Director:||Francois Lebel, MD||ZIOPHARM Oncology|