36 Participants Needed

Virus Therapy for Brain Tumors

FL
Overseen ByFrederick Lang
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called DNX-2401, which uses a modified cold virus to target and attack brain tumor cells in individuals with recurring high-grade glioma. Researchers aim to determine the optimal dose and monitor any side effects. The trial involves two parts: administering the virus directly into the brain tumor and, in some cases, performing surgery followed by another dose of the virus. It seeks participants with brain tumors, such as glioblastoma, that have returned and are confirmed to be growing after previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop taking other cytotoxic and non-cytotoxic drugs or radiation therapy against the tumor while enrolled. Additionally, there are specific time periods that must be observed after completing certain chemotherapies before starting the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that DNX-2401, the treatment under study, is safe based on earlier studies. It has been tested in people with brain tumors, and results indicate that DNX-2401 is well-tolerated and can specifically target and attack brain cancer cells.

In one study, DNX-2401 was safe and able to multiply within tumors, allowing it to fight cancer cells without causing serious side effects. Another study tested DNX-2401 alongside another treatment, and it remained safe, suggesting that DNX-2401 does not cause harmful reactions even when combined with other treatments.

Based on these studies, DNX-2401 appears safe for people with recurring high-grade glioma. However, like any treatment, there is always a chance of side effects, which is why ongoing research and clinical trials remain important.12345

Why do researchers think this study treatment might be promising?

Most treatments for brain tumors involve surgery, radiation, and chemotherapy, which can harm healthy cells and tissues. However, DNX-2401 offers a unique approach by using an oncolytic adenovirus that specifically targets and destroys cancer cells without affecting normal cells. This virus therapy is exciting because it not only attacks tumors directly but also stimulates the body's immune system to recognize and fight the cancer. Researchers are hopeful that this dual action could lead to more effective treatment outcomes and fewer side effects for brain tumor patients.

What evidence suggests that DNX-2401 might be an effective treatment for brain tumors?

Research has shown that DNX-2401, a type of virus, can effectively target and destroy glioma cells, a kind of brain cancer cell. In human studies, this virus multiplied inside the tumor, leading to the breakdown of cancer cells. The trial includes two parts: in Part I, participants receive the oncolytic adenovirus Ad5-DNX-2401 alone, while in Part II, participants receive the virus followed by surgery and an additional dose of the virus. This treatment specifically targets brain cancer cells, such as those in aggressive gliomas, while leaving healthy cells unharmed. Early findings suggest that DNX-2401 may cause tumor cells to die through virus-related processes. Although the therapy is still under study, these initial results are promising for treating recurring brain tumors.12367

Who Is on the Research Team?

FF

Frederick F Lang

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults with recurrent high-grade glioma, such as glioblastoma or astrocytoma, who have tried surgery, chemotherapy, or radiation before. They must be in good enough health to undergo endovascular treatment and have a life expectancy of at least 16 weeks. Participants need a tumor size between 1-5 cm and a Karnofsky score ≥70 (able to care for themselves). Pregnant women are excluded.

Inclusion Criteria

My tumor can be removed surgically, and I need a surgery to remove part of my skull to access it.
My recurrent brain tumor does not have IDH-1 mutation and shows a significant mass on MRI.
It has been at least 8 weeks since my last radiotherapy session.
See 15 more

Exclusion Criteria

My cancer has spread to the lining of my brain and spinal cord.
I have trouble getting IV lines placed for procedures.
I haven't had biologic or immunotherapy in the last 2 weeks.
See 20 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part I

Patients receive one or two infusions of BM-hMSCs-DNX-2401 intra-arterially over 20-30 minutes on day 0. Dose level 1-5 will receive 1 infusion. Dose level 6 will receive 2 infusions.

1 day
1 visit (in-person)

Treatment Part II

Patients receive one or two infusions of BM-hMSCs-DNX-2401 IA, depending on the highest dose tolerated in Part 1. After 2 weeks, patients undergo surgery where the tumor is removed, then receive intramural injection of BM-hMSCs-DNX-2401 into the resection cavity.

2 weeks
1 visit (in-person) for surgery

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs on days 1, 4, 7, and 14 of month 1, every 6 weeks for 6 months, then every 8 weeks for 1 year, then every 4 months for 1 year, then every 6 months until the tumor grows back.

Up to 2 years
Multiple visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

  • DNX-2401
Trial Overview The trial is testing the safety and optimal dose of DNX-2401, an altered cold virus targeting brain cancer cells. It's given after conventional surgery to see if it can help treat recurrent high-grade gliomas more effectively than current treatments.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Part II (oncolytic adenovirus Ad5-DNX-2401, surgery)Experimental Treatment2 Interventions
Group II: Part I (oncolytic adenovirus Ad5-DNX-2401)Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

DNAtrix, Inc.

Industry Sponsor

Trials
8
Recruited
250+

Published Research Related to This Trial

In a phase I clinical trial involving 37 patients with recurrent malignant glioma, DNX-2401 demonstrated significant efficacy, with 20% of patients surviving over 3 years and three patients experiencing a greater than 95% reduction in tumor size.
The treatment not only caused direct oncolysis of tumor cells but also triggered an immune response, as evidenced by increased infiltration of immune cells and signs of immunogenic cell death, suggesting a dual mechanism of action for DNX-2401.
Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic Adenovirus: Replication and Immunotherapeutic Effects in Recurrent Malignant Glioma.Lang, FF., Conrad, C., Gomez-Manzano, C., et al.[2023]
The oncolytic virus Delta-24-RGD has been shown to be safe and significantly increase survival in mouse models of pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs), indicating its potential as a treatment option.
The therapeutic effect of Delta-24-RGD is attributed to both its ability to directly kill tumor cells and to stimulate an immune response against the tumors, leading to the initiation of a phase I/II clinical trial for newly diagnosed DIPG patients.
The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models.Martínez-Vélez, N., Garcia-Moure, M., Marigil, M., et al.[2021]
DNX-2401, an oncolytic adenovirus, has shown a favorable safety profile in adults with glioblastoma and is being tested in a Phase I trial for pediatric patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPG), which currently have no curative treatment.
The first case report of an 8-year-old patient receiving intratumoral DNX-2401 after a biopsy indicated no safety concerns or neurological deficits, suggesting that this approach may be a feasible and innovative treatment option for DIPG.
DNX-2401, an Oncolytic Virus, for the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Gliomas: A Case Report.Tejada, S., Díez-Valle, R., Domínguez, PD., et al.[2020]

Citations

Oncolytic DNX-2401 virotherapy plus pembrolizumab in ...This is the first in-human investigation of combined oncolytic virus with immune checkpoint blockade for recurrent glioblastoma.
Phase I Study of DNX-2401 (Delta-24-RGD) Oncolytic ...These data demonstrate the ability of DNX-2401 to lyse glioma cells and provide evidence for active oncolytic adenovirus replication in human ...
MSC-DNX-2401 in Treating Patients With Recurrent High- ...This phase I trial studies best dose and side effects of oncolytic adenovirus DNX-2401 in treating patients with high-grade glioma that has come back ...
Oncolytic immunovirotherapy for high-grade gliomasDNX-2401 demonstrated a virus-mediated mechanism of tumor cell necrosis (48). A phase I, dose-escalation clinical trial was the first to ...
MSC-DNX-2401 in Treating Patients With Recurrent High ...This phase I trial studies best dose and side effects of oncolytic adenovirus DNX-2401 in treating patients with high-grade glioma that has come back ...
Chimeric oncolytic adenovirus evades neutralizing ...In this work, we showed that antibodies are found colocalized with virus proteins in the brain tumors of mice treated with Delta-24-RGD. Based ...
A Phase I Clinical Trial Including Correlative Studies - PMCTesting safety of Delta24-RGD (DNX-2401), an oncolytic adenovirus, locally delivered by convection enhanced delivery (CED) in tumor and surrounding brain of ...
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