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

Glioblastoma or Gliosarcoma Clinical Trial

— TARGET-I  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02197169
• Other study ID #: 2401BT-IFN-001
• Status: Completed
• Phase: Phase 1
• Start date: September 11, 2014
• Est. completion date: March 15, 2018

Study information

• Verified date: July 2018
• Source: DNAtrix, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: March 15, 2018
• Est. primary completion date: March 15, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma or Gliosarcoma
• Gliosarcoma

Intervention

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-?) No additional subjects will be randomized. A single intratumoral dose of DNX-2401 will be delivered by cannula.
• Interferon-gamma
In the randomized group, a single injection of DNX-2401 was followed by interferon gamma (IFN-?). No additional subjects will be randomized or receive IFN-? following DNX-2401

Locations

Country	Name	City	State
United States	The Ohio State University	Columbus	Ohio
United States	Baylor University: Charles A. Sammons Cancer Center	Dallas	Texas
United States	UT MD Anderson Cancer Center	Houston	Texas
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
DNAtrix, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate (ORR) determined by MRI scan review	Interval tumor size change will be measured	1.5 years
Secondary	Incidence and severity of adverse events, including changes in laboratory test results and neurological examination findings	Events are classified using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03	1.5 years
Secondary	Number of subjects with immunological and biological effects after DNX-2401 with Interferon gamma	Laboratory test results and other assessments will be utilized to determine effects	1.5 years
Secondary	Changes in steroid use (dose and frequency) and clinical and KPS status overall and per study arm assignment		1.5 years
Secondary	Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).		1.5 years
Secondary	Changes in responses to quality of life questionnaires		1.5 years