Glioblastoma or GliosarcomaPhase 1TARGET-INCT02197169
DNX-2401 With Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma Brain Tumors
A Phase 1 study testing Single intratumoral injection of DNX-2401 and Interferon-gamma in people with Glioblastoma or Gliosarcoma, run by DNAtrix, Inc. at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma or Gliosarcoma
- What is being tested?
- Single intratumoral injection of DNX-2401 and Interferon-gamma
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 4 sitesUnited States
- Study dates
- 11 Sep 2014to 15 Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
The Ohio State University
Columbus, Ohio, 43210
Baylor University: Charles A. Sammons Cancer Center
Dallas, Texas, 75246
UT MD Anderson Cancer Center
Houston, Texas, 77030
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
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)
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.
Read the 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.
- Conditions
- Glioblastoma or Gliosarcoma
- Being tested
- Single intratumoral injection of DNX-2401, Interferon-gamma
- 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
- Medical subject headings
- Glioblastoma, Gliosarcoma, Brain Neoplasms, Central Nervous System Diseases, Central Nervous System Neoplasms, Glioma, Neoplasms, Neuroepithelial, Neuroectodermal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Single intratumoral injection of DNX-2401Drug
Also called Oncolytic virus, Genetically-modified adenovirus
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.
Interferon-gammaDrug
Also called Actimmune, immunotherapy, gamma interferon
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
| Study group | Role | What they receive |
|---|---|---|
| DNX-2401 alone | Experimental | Single intratumoral injection of DNX-2401 Receives: Drug: Single intratumoral injection of DNX-2401 |
| DNX-2401 + Interferon gamma (IFN-γ) | Experimental | Interferon gamma (IFN-γ) beginning at Day 14 Receives: Drug: Single intratumoral injection of DNX-2401; Drug: Interferon-gamma |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR) determined by MRI scan review
Interval tumor size change will be measured
Measured: 1.5 years
Secondary outcomes (5)
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
Measured: 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
Measured: 1.5 years
Changes in steroid use (dose and frequency) and clinical and KPS status overall and per study arm assignment
Measured: 1.5 years
Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).
Measured: 1.5 years
Changes in responses to quality of life questionnaires
Measured: 1.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2014 (estimated)
- Study start11 Sep 2014
- Primary completion15 Mar 2018
- Study completion15 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glioblastoma or GliosarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- DNAtrix, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Nam Tran, MD, PhD, Principal investigator, Moffitt Cancer CenterKaren Fink, MD, PhD, Principal investigator, Baylor University: Charles A. Sammons Cancer CenterVinay Puduvalli, MBBS, Principal investigator, Ohio State University: James Cancer CenterFrederick Lang, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02197169
- Sponsor's protocol ID
- 2401BT-IFN-001
- Acronym
- TARGET-I
- Status last verified
- Jul 2018
- First submitted
- 20 Jul 2014
- Last updated
- 16 Jul 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02197169
- Acronym / sponsor ID
- TARGET-I / 2401BT-IFN-001
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- DNAtrix, Inc.Industry (pharma, biotech, devices)
- Study start
- 11 Sep 2014 (actual)
- Primary completion
- 15 Mar 2018 (actual)
- Study completion
- 15 Mar 2018 (actual)
- First posted
- 22 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DNX-2401 alone | Experimental | Drug: Single intratumoral injection of DNX-2401Single intratumoral injection of DNX-2401 |
| DNX-2401 + Interferon gamma (IFN-γ) | Experimental | Drug: Single intratumoral injection of DNX-2401, Drug: Interferon-gammaInterferon gamma (IFN-γ) beginning at Day 14 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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%
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Single intratumoral injection of DNX-2401Also: Oncolytic virus, Genetically-modified adenovirusIn 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. | Drug | DNX-2401 + Interferon gamma (IFN-γ), DNX-2401 alone |
| Interferon-gammaAlso: Actimmune, immunotherapy, gamma interferonIn 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 | Drug | DNX-2401 + Interferon gamma (IFN-γ) |
Primary outcome
Objective response rate (ORR) determined by MRI scan review
Time frame: 1.5 years
Interval tumor size change will be measured
5 secondary outcomes
Incidence and severity of adverse events, including changes in laboratory test results and neurological examination findings
Time frame: 1.5 years
Number of subjects with immunological and biological effects after DNX-2401 with Interferon gamma
Time frame: 1.5 years
Changes in steroid use (dose and frequency) and clinical and KPS status overall and per study arm assignment
Time frame: 1.5 years
Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).
Time frame: 1.5 years
Changes in responses to quality of life questionnaires
Time frame: 1.5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nam Tran, MD, PhD principal investigator
Moffitt Cancer Center
Karen Fink, MD, PhD principal investigator
Baylor University: Charles A. Sammons Cancer Center
Vinay Puduvalli, MBBS principal investigator
Ohio State University: James Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Single intratumoral injection of DNX-2401 and Interferon-gamma in people with Glioblastoma or Gliosarcoma, run by DNAtrix, Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) determined by MRI scan review (time frame: 1.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2018.