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

Phase 1
Completed
Conditions
Glioblastoma or Gliosarcoma
Interventions
Drug: Single intratumoral injection of DNX-2401
Registration Number
NCT02197169
Lead Sponsor
DNAtrix, Inc.
Brief 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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
37
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
DNX-2401 + Interferon gamma (IFN-γ)Single intratumoral injection of DNX-2401Interferon gamma (IFN-γ) beginning at Day 14
DNX-2401 aloneSingle intratumoral injection of DNX-2401Single intratumoral injection of DNX-2401
DNX-2401 + Interferon gamma (IFN-γ)Interferon-gammaInterferon gamma (IFN-γ) beginning at Day 14
Primary Outcome Measures
NameTimeMethod
Objective response rate (ORR) determined by MRI scan review1.5 years

Interval tumor size change will be measured

Secondary Outcome Measures
NameTimeMethod
Number of subjects with immunological and biological effects after DNX-2401 with Interferon gamma1.5 years

Laboratory test results and other assessments will be utilized to determine effects

Changes in responses to quality of life questionnaires1.5 years
Incidence and severity of adverse events, including changes in laboratory test results and neurological examination findings1.5 years

Events are classified using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

Changes in steroid use (dose and frequency) and clinical and KPS status overall and per study arm assignment1.5 years
Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).1.5 years

Trial Locations

Locations (4)

The Ohio State University

🇺🇸

Columbus, Ohio, United States

Baylor University: Charles A. Sammons Cancer Center

🇺🇸

Dallas, Texas, United States

Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

UT MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

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