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

NCT02197169 | Completed Phase 1

• 1 other identifier: 2401BT-IFN-001
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 4

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.

Conditions

Glioblastoma or Gliosarcoma

Keywords

Brain; Brain Cancer; Brain Neoplasms; Central Nervous System Diseases; Central Nervous System Neoplasms; CNS; Conditionally Replication-Competent Adenovirus; DNX-2401; Delta-24-RGD; Glioma; Glioblastoma; Gliosarcoma; 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

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) determined by MRI scan review

  Interval tumor size change will be measured

  1.5 years

Secondary Outcomes (5)

• Incidence and severity of adverse events, including changes in laboratory test results and neurological examination findings

  1.5 years

• Number of subjects with immunological and biological effects after DNX-2401 with Interferon gamma

  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

Study Arms (2)

DNX-2401 alone

EXPERIMENTAL

Single intratumoral injection of DNX-2401

Drug: Single intratumoral injection of DNX-2401

DNX-2401 + Interferon gamma (IFN-γ)

EXPERIMENTAL

Interferon gamma (IFN-γ) beginning at Day 14

Drug: Single intratumoral injection of DNX-2401; Drug: Interferon-gamma

Interventions

Single intratumoral injection of DNX-2401 DRUG

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.

Also known as: Oncolytic virus, Genetically-modified adenovirus

DNX-2401 + Interferon gamma (IFN-γ); DNX-2401 alone

Interferon-gamma DRUG

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

Also known as: Actimmune, immunotherapy, gamma interferon

DNX-2401 + Interferon gamma (IFN-γ)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• DNAtrix, Inc.: lead

Study Sites (4)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Baylor University: Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Brain Neoplasms; Central Nervous System Diseases; Central Nervous System Neoplasms; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Nervous System Diseases

Interventions

Oncolytic Virotherapy; Interferon-gamma; interferon gamma-1b; Immunotherapy

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Macrophage-Activating Factors; Lymphokines; Proteins; Biological Factors; Immunomodulation

Study Officials

• Nam Tran, MD, PhD

  Moffitt Cancer Center

  PRINCIPAL INVESTIGATOR

• Karen Fink, MD, PhD

  Baylor University: Charles A. Sammons Cancer Center

  PRINCIPAL INVESTIGATOR

• Vinay Puduvalli, MBBS

  Ohio State University: James Cancer Center

  PRINCIPAL INVESTIGATOR

• Frederick Lang, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2014
• First Posted: July 22, 2014
• Study Start: September 11, 2014
• Primary Completion: March 15, 2018
• Study Completion: March 15, 2018
• Last Updated: July 16, 2018

Record last verified: 2018-07

Locations

US (4)