Clinical Trial: A Study of Ad-RTS-hIL-12 With Veledimex in Subjects With Glioblastoma or Malignant Glioma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 o

Brief Summary:

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.


Detailed Summary:

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.


Sponsor: Ziopharm

Current Primary Outcome: 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.


Original Primary Outcome: Safety and tolerability of a single intra tumor Ad-RTS-hIL-12 dose (1.0x1012 viral particles) plus escalating oral veledimex doses in subjects with recurrent or progressive glioblastoma or Grade III malignant gliomas [ 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.


Current Secondary Outcome:

  • 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 ]


Original Secondary Outcome:

  • Veledimex maximum tolerated dose (MTD) when given with a single intra tumor Ad-RTS-hIL-12 dose (1.0x1012 viral particles) [ Time Frame: 3 years ]
  • Veledimex pharmacokinetic profile and distribution to the tumor [ 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 ]


Information By: Ziopharm

Dates:
Date Received: December 16, 2013
Date Started: June 2015
Date Completion: December 2019
Last Updated: February 13, 2017
Last Verified: February 2017