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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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Glioblastoma or Gliosarcoma

Intervention / Treatment
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* Drug: Single intratumoral injection of DNX-2401
* Drug: Interferon-gamma


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DNX-2401 alone<br>Single intratumoral injection of DNX-2401 | Drug: Single intratumoral injection of DNX-2401<br>* 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.<br>* Other names: Genetically-modified adenovirus;|
| Experimental: DNX-2401 + Interferon gamma (IFN-γ)<br>Interferon gamma (IFN-γ) beginning at Day 14 | Drug: Single intratumoral injection of DNX-2401<br>* 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.<br>* Other names: Genetically-modified adenovirus;Drug: Interferon-gamma<br>* 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<br>* Other names: gamma interferon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) determined by MRI scan review | 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 | 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 | 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 |  | 1.5 years | 
| Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR). |  | 1.5 years | 
| Changes in responses to quality of life questionnaires |  | 1.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gliosarcoma, DNX-2401, Brain, Brain Cancer, Brain Neoplasms, Central Nervous System Diseases, Central Nervous System Neoplasms, CNS, Conditionally Replication-Competent Adenovirus, Delta-24-RGD, Glioma, Glioblastoma, Interferon gamma, Malignant brain tumor, Neoplasms, Neuroepithelial, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Neoplasms by Histologic Type, Neoplasms, Glandular and Epithelial, Neoplasms, Nerve Tissue, Nervous System Diseases, Alcyone Lifesciences, AMC™, Cannula, Alcyone MEMS Cannula (AMC™) System