Back to resultsDNX-2401 With Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma Brain Tumors (TARGET-I)
Primary Purpose
Glioblastoma or Gliosarcoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Single intratumoral injection of DNX-2401
Interferon-gamma
Sponsored by
About this trial
This is an interventional treatment trial for Glioblastoma or Gliosarcoma focused on measuring 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
Eligibility Criteria
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
Sites / Locations
- Moffitt Cancer Center
- The Ohio State University
- Baylor University: Charles A. Sammons Cancer Center
- UT MD Anderson Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
DNX-2401 alone
DNX-2401 + Interferon gamma (IFN-γ)
Arm Description
Single intratumoral injection of DNX-2401
Interferon gamma (IFN-γ) beginning at Day 14
Outcomes
Primary Outcome Measures
Objective response rate (ORR) determined by MRI scan review
Interval tumor size change will be measured
Secondary Outcome Measures
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
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
Changes in steroid use (dose and frequency) and clinical and KPS status overall and per study arm assignment
Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).
Changes in responses to quality of life questionnaires
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02197169
Brief Title
DNX-2401 With Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma Brain Tumors
Acronym
TARGET-I
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
September 11, 2014 (Actual)
Primary Completion Date
March 15, 2018 (Actual)
Study Completion Date
March 15, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
DNAtrix, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DNX-2401 alone
Arm Type
Experimental
Arm Description
Single intratumoral injection of DNX-2401
Arm Title
DNX-2401 + Interferon gamma (IFN-γ)
Arm Type
Experimental
Arm Description
Interferon gamma (IFN-γ) beginning at Day 14
Intervention Type
Drug
Intervention Name(s)
Single intratumoral injection of DNX-2401
Other Intervention Name(s)
Oncolytic virus, Genetically-modified adenovirus
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Interferon-gamma
Other Intervention Name(s)
Actimmune, immunotherapy, gamma interferon
Intervention Description
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
Primary Outcome Measure Information:
Title
Objective response rate (ORR) determined by MRI scan review
Description
Interval tumor size change will be measured
Time Frame
1.5 years
Secondary Outcome Measure Information:
Title
Incidence and severity of adverse events, including changes in laboratory test results and neurological examination findings
Description
Events are classified using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Time Frame
1.5 years
Title
Number of subjects with immunological and biological effects after DNX-2401 with Interferon gamma
Description
Laboratory test results and other assessments will be utilized to determine effects
Time Frame
1.5 years
Title
Changes in steroid use (dose and frequency) and clinical and KPS status overall and per study arm assignment
Time Frame
1.5 years
Title
Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).
Time Frame
1.5 years
Title
Changes in responses to quality of life questionnaires
Time Frame
1.5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nam Tran, MD, PhD
Organizational Affiliation
Moffitt Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Karen Fink, MD, PhD
Organizational Affiliation
Baylor University: Charles A. Sammons Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Vinay Puduvalli, MBBS
Organizational Affiliation
Ohio State University: James Cancer Center
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Frederick Lang, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Baylor University: Charles A. Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
UT MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
DNX-2401 With Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma Brain Tumors
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