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

Phase 1CompletedNCT02197169

DNAtrix, Inc.37 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Glioblastoma or Gliosarcoma

Interventions

Single intratumoral injection of DNX-2401DRUG

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.

Interferon-gammaDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (4)

Moffitt Cancer Center

Tampa, Florida, 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

Outcomes

Primary Outcomes

Objective response rate (ORR) determined by MRI scan review

Interval tumor size change will be measured

Time frame: 1.5 years

Secondary Outcomes

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

Time frame: 1.5 years

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

Time frame: 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

Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).

Time frame: 1.5 years

Changes in responses to quality of life questionnaires

Time frame: 1.5 years

Data from ClinicalTrials.gov

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