Clinical trial NCT02197169: DNX-2401 With Interferon Gamma (IFN-γ) for Recurrent Glioblastoma or Gliosarcoma Brain Tumors
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
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: DNAtrix, Inc.
Sponsor class: INDUSTRY
First posted: 2014-07-22
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective response rate (ORR) determined by MRI scan review
timeFrame: 1.5 years
Secondary outcomes:
measure: Incidence and severity of adverse events, including changes in laboratory test results and neurological examination findings
timeFrame: 1.5 years
measure: Number of subjects with immunological and biological effects after DNX-2401 with Interferon gamma
timeFrame: 1.5 years
measure: Changes in steroid use (dose and frequency) and clinical and KPS status overall and per study arm assignment
timeFrame: 1.5 years
measure: Overall survival (OS), progression-free survival (PFS), and clinical benefit rate (CBR).
timeFrame: 1.5 years
measure: Changes in responses to quality of life questionnaires
timeFrame: 1.5 years
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Dallas
country: United States
facility: Baylor University: Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: UT MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Moffitt Cancer Center
name: Nam Tran, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Baylor University: Charles A. Sammons Cancer Center
name: Karen Fink, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ohio State University: James Cancer Center
name: Vinay Puduvalli, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Frederick Lang, MD
role: PRINCIPAL_INVESTIGATOR
References: