DNX-2401 With Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma Brain Tumors (TARGET-I)

July 12, 2018 updated by: DNAtrix, Inc.

A Phase 1b, Randomized, Multi-center, Open-label Study of a Conditionally Replicative Adenovirus (DNX-2401) and Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma (TARGET-I)

Glioblastoma (GBM) and gliosarcoma (GS) are the most common and aggressive forms of malignant primary brain tumor in adults and can be resistant to conventional therapies. The purpose of this Phase Ib study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor responds to one injection of DNX-2401, a genetically modified, conditionally replicative and oncolytic human-derived adenovirus. DNX-2401 is delivered directly into the tumor where it may establish an active infection by replicating in and killing tumor cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Enrollment has been completed for the randomized portion of the study with ongoing evaluation of tumor response and safety. No additional subjects will be randomized or receive interferon gamma (IFN-γ).

The non-randomized portion of the study is open for screening and enrollment. Eligible subjects will receive a single intratumoral injection of DNX-2401 into a recurrent glioblastoma or gliosarcoma brain tumor using the Alcyone MEMS Cannula (AMC™) System (cannula). Tumor response and safety will be evaluated.

After receiving DNX-2401, subjects will return to the clinic for study visits at regular intervals for safety monitoring, MRI scans and other assessments for up to 18 months. Thereafter, they will be followed closely for safety and survival.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University: Charles A. Sammons Cancer Center
      • Houston, Texas, United States, 77030
        • UT MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Glioblastoma or gliosarcoma in first or second recurrence only
  • Documented tumor recurrence or progression after failing prior surgical resection, chemotherapy, or radiation
  • Tumor size greater than or equal to 1.0 cm in two perpendicular diameters
  • Not undergoing surgical resection or for whom gross total resection is not possible
  • Karnofsky Performance Status greater than or equal to 70%

Exclusion Criteria:

  • Multiple intracranial malignant glioma lesions
  • Tumor location or involvement that would result in risk of ventricular penetration during tumor injection
  • Tumor involving both hemispheres or that which involves the subependyma or suspected cerebrospinal fluid dissemination
  • Tumor involving brain stem
  • Documented extracranial metastasis
  • Inability to undergo MRI
  • Pregnant or nursing females
  • Any medical condition that precludes the surgery necessary to administer DNX-2401 into the tumor using the cannula
  • Immunocompromised subjects or those with autoimmune conditions, active hepatitis or positive for human immunodeficiency virus (HIV)
  • Li-Fraumeni Syndrome

Other protocol-defined inclusion/exclusion criteria may apply as outlined in the relevant protocol version

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: DNX-2401 alone
Single intratumoral injection of DNX-2401
Drug: Single intratumoral injection of DNX-2401

In the randomized group, following brain tumor biopsy and histological confirmation of recurrent glioblastoma/gliosarcoma, a single injection of DNX-2401 was administered directly into the brain tumor with or without subsequent interferon gamma (IFN-γ)

No additional subjects will be randomized. A single intratumoral dose of DNX-2401 will be delivered by cannula.

Other Names:
  • Oncolytic virus
  • Genetically-modified adenovirus
Experimental: DNX-2401 + Interferon gamma (IFN-γ)
Interferon gamma (IFN-γ) beginning at Day 14
Drug: Single intratumoral injection of DNX-2401

In the randomized group, following brain tumor biopsy and histological confirmation of recurrent glioblastoma/gliosarcoma, a single injection of DNX-2401 was administered directly into the brain tumor with or without subsequent interferon gamma (IFN-γ)

No additional subjects will be randomized. A single intratumoral dose of DNX-2401 will be delivered by cannula.

Other Names:
  • Oncolytic virus
  • Genetically-modified adenovirus
Drug: Interferon-gamma
In the randomized group, a single injection of DNX-2401 was followed by interferon gamma (IFN-γ). No additional subjects will be randomized or receive IFN-γ following DNX-2401
Other Names:
  • immunotherapy
  • Actimmune
  • gamma interferon

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective response rate (ORR) determined by MRI scan review
Time Frame: 1.5 years
Interval tumor size change will be measured
1.5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of adverse events, including changes in laboratory test results and neurological examination findings
Time Frame: 1.5 years
Events are classified using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
1.5 years
Number of subjects with immunological and biological effects after DNX-2401 with Interferon gamma
Time Frame: 1.5 years
Laboratory test results and other assessments will be utilized to determine effects
1.5 years
Changes in steroid use (dose and frequency) and clinical and KPS status overall and per study arm assignment
Time Frame: 1.5 years
1.5 years
Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).
Time Frame: 1.5 years
1.5 years
Changes in responses to quality of life questionnaires
Time Frame: 1.5 years
1.5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

DNAtrix, Inc.

Investigators

  • Principal Investigator: Nam Tran, MD, PhD, Moffitt Cancer Center
  • Principal Investigator: Karen Fink, MD, PhD, Baylor University: Charles A. Sammons Cancer Center
  • Principal Investigator: Vinay Puduvalli, MBBS, Ohio State University: James Cancer Center
  • Principal Investigator: Frederick Lang, MD, M.D. Anderson Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 11, 2014

Primary Completion (Actual)

March 15, 2018

Study Completion (Actual)

March 15, 2018

Study Registration Dates

First Submitted

July 20, 2014

First Submitted That Met QC Criteria

July 20, 2014

First Posted (Estimate)

July 22, 2014

Study Record Updates

Last Update Posted (Actual)

July 16, 2018

Last Update Submitted That Met QC Criteria

July 12, 2018

Last Verified

July 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2401BT-IFN-001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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