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Combination Adenovirus + Pembrolizumab to Trigger Immune Virus Effects

Study Purpose

Glioblastoma (GBM) and gliosarcoma (GS) are the most common and aggressive forms of malignant brain tumor in adults and can be resistant to conventional therapies. The purpose of this Phase II study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor responds to one injection of DNX-2401, a genetically modified oncolytic adenovirus, when delivered directly into the tumor followed by the administration of intravenous pembrolizumab (an immune checkpoint inhibitor) given every 3 weeks for up to 2 years or until disease progression. Funding Source-FDA OOPD

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - A single glioblastoma or gliosarcoma tumor with histopathological confirmation for first or presenting second recurrence of glioblastoma or gliosarcoma at the time of consent.
  • - Gross total or partial tumor resection is not possible or not planned.
  • - A single measurable tumor that is at least 10.0 mm longest diameter (LDi) X 10.0 mm shortest diameter (SDi) and this tumor does not exceed 40.0 mm in LDi or SDi on Screening MRI.
  • - Tumor recurrence or progression documented after previously failing surgical resection, chemotherapy or radiation.
  • - Karnofsky performance status ≥ 70 % - Prior anti-tumor therapies must have been completed within time periods specified in the protocol prior to DNX-2401 injection and toxic side effects must be mild, if present.
  • - Demonstrate adequate organ function via specified laboratory test results.

Exclusion Criteria:

  • - Multiple (≥ 2) separate enhancing tumors.
  • - Tumor location on both sides of the brain and/or involvement that would present the risk of injecting DNX-2401 into the ventricles of the brain.
  • - Tumor location in the brain stem.
  • - Requires or, based upon history, may require treatment with high-dose systemic corticosteroids within 2 weeks of the start of intravenous pembrolizumab infusions and within 2 weeks following the first infusion of pembrolizumab.
  • - Uncontrolled blood-sugar levels defined as HbA1c > 7% - Previous treatment with any checkpoint inhibitor such as anti-PD1 or PD-L1 agents including pembrolizumab (KEYTRUDA) or any other checkpoint inhibitor(s) (e.g., ipilimumab, nivolumab, etc.) - History of (non-infectious) or current active pneumonitis that required steroids and/or a history of interstitial lung disease.
  • - Prior gene transfer therapy or prior therapy with a cytolytic virus of any type.
  • - Brain tumor that is not measurable on MRI or persons who are unable to have MRIs.
  • - Pregnant or nursing females.
Note: Other protocol-defined inclusion and exclusion criteria may apply as outlined in the relevant protocol version

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02798406
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

DNAtrix, Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Nancy Gady, BS
Principal Investigator Affiliation DNAtrix, Inc.
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Completed
Countries Canada, United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Brain Cancer, Brain Neoplasm, Glioma, Glioblastoma, Gliosarcoma, Malignant Brain Tumor, Neoplasm, Neuroepithelial, Neuroectodermal Tumors, Neoplasm by Histologic Type, Neoplasm, Nerve Tissue, Nervous System Diseases
Additional Details

In the initial phase of the study, up to 12 evaluable subjects will be enrolled in 3 dose cohorts to determine the best dose of DNX-2401, as follows:

  • - Cohort 1: Single dose DNX-2401 (5e8 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W) - Cohort 2: Single dose DNX-2401(5e9 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W) - Cohort 3: Single dose DNX-2401 (5e10 vp) delivered intratumorally by cannula, followed by intravenous pembrolizumab every 3 weeks (Q3W) Following the initial phase, up to 36 additional subjects diagnosed with recurrent glioblastoma or gliosarcoma will be enrolled to receive a single of DNX-2401 determined in the initial phase administered intratumorally followed by intravenous pembrolizumab every 3 weeks.
All subjects will return to the clinic for study follow-up visits at regular intervals for safety monitoring, MRI scans and other assessments, for up to 2 years or until disease progression. All subjects will be followed closely for safety and survival.

Arms & Interventions

Arms

Experimental: DNX-2401 + pembrolizumab

Intratumoral dose (1.0 mL) of DNX-2401 followed 7-9 days later by intravenous pembrolizumab, 200 mg, given every three weeks through 105 weeks (2 yrs.) or until progressive disease or unacceptable toxicity.

Interventions

Biological: - DNX-2401

On Day 0, following brain tumor biopsy and confirmation of recurrent tumor, a single injection of DNX-2401 is administered directly into the brain tumor.

Biological: - pembrolizumab

Sequential intravenous administration every three weeks beginning 7-9 days after Day 0/DNX-2401

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Little Rock, Arkansas

Status

Address

University of Arkansas for Medical Sciences (UAMS)

Little Rock, Arkansas, 72205

UCLA Medical Center, Los Angeles, California

Status

Address

UCLA Medical Center

Los Angeles, California, 90095

Northwestern University, Chicago, Illinois

Status

Address

Northwestern University

Chicago, Illinois, 60611

University of Minnesota Neurosurgery, Minneapolis, Minnesota

Status

Address

University of Minnesota Neurosurgery

Minneapolis, Minnesota, 55455

Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey

Status

Address

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903

Memorial Sloan Kettering Cancer Center, New York, New York

Status

Address

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

New York, New York

Status

Address

Weill-Cornell Medicine New York-Presbyterian

New York, New York, 10065

Chapel Hill, North Carolina

Status

Address

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27514

Cleveland Clinic, Cleveland, Ohio

Status

Address

Cleveland Clinic

Cleveland, Ohio, 44195

Columbus, Ohio

Status

Address

Ohio State University James Cancer Center

Columbus, Ohio, 43210

Lehigh Valley Health Network, Allentown, Pennsylvania

Status

Address

Lehigh Valley Health Network

Allentown, Pennsylvania, 18103

Texas Oncology Austin-Midtown, Austin, Texas

Status

Address

Texas Oncology Austin-Midtown

Austin, Texas, 78705

MD Anderson Cancer Center, Houston, Texas

Status

Address

MD Anderson Cancer Center

Houston, Texas, 77030

Huntsman Cancer Institute, Salt Lake City, Utah

Status

Address

Huntsman Cancer Institute

Salt Lake City, Utah, 84112

International Sites

University Health Network, Toronto, Ontario, Canada

Status

Address

University Health Network

Toronto, Ontario, M5T 2S8