Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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:
    • Actimmune
    • immunotherapy
    • gamma interferon

Recruiting Locations

More Details

NCT ID
NCT02197169
Status
Completed
Sponsor
DNAtrix, Inc.

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.