What side effects are associated with this type of intervention?

Common treatments for brain tumors, such as Retifanlimab (an anti-PD-1 antibody), Radiation Therapy, Bevacizumab (an anti-VEGF antibody), and Epacadostat (an IDO1 inhibitor), have various side effects. Retifanlimab can cause immune-related adverse events like pneumonitis, colitis, hepatitis, and endocrinopathies. Radiation therapy often leads to fatigue, skin changes, and potential long-term effects like cognitive decline and radiation necrosis. Bevacizumab is associated with hypertension, increased risk of bleeding, thromboembolic events, and gastrointestinal perforations. Epacadostat, while still under investigation, may cause fatigue, rash, and gastrointestinal disturbances. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

Bevacizumab, an anti-VEGF antibody, received accelerated FDA approval for the treatment of recurrent glioblastoma. Temozolomide, often used in conjunction with radiation therapy, is a standard treatment for newly diagnosed glioblastoma. Anti-PD-1 antibodies like nivolumab and pembrolizumab have been explored in clinical trials for recurrent glioblastoma, though their efficacy has shown limited clinical benefit. IDO1 inhibitors, such as epacadostat, are still under investigation and have not yet received FDA approval for brain tumors.

What other types of research exist?

Promising novel alternatives for brain tumor treatment in 2024 include: 1) Everolimus (mTORC1 inhibitor), 2) Lapatinib (EGFR and HER2 inhibitor), 3) ONC201 (selective DRD2 antagonist), and 4) other antiangiogenic agents such as cediranib. These alternatives target various pathways involved in tumor growth and may offer new therapeutic options for brain tumor patients.

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Angiogenesis Inhibitor

Combination Therapy + Radiation for Glioblastoma

Phase 2

Waitlist Available

Led By Jian L Campian, M.D., Ph.D.

Research Sponsored by Washington University School of Medicine

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Recurrent WHO grade 4 glioblastoma or gliosarcoma, including molecular features of glioblastoma and WHO grade 4 astrocytoma or WHO grade high grade glioma

At least 18 years of age

Must not have

Various autoimmune diseases or syndromes requiring systemic treatment

Uncontrolled HIV or active hepatitis B or C

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through 2 years after completion of treatment (estimated to be 4 years)

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of treatments including a new drug, radiation therapy, and other medications for patients with aggressive brain cancer that has returned. The goal is to boost the body's immune system to better fight the cancer, shrink tumors, and help patients live longer.

Who is the study for?

This trial is for adults with recurrent grade 4 glioblastoma or gliosarcoma who have measurable disease, normal organ and bone marrow function, and a Karnofsky performance status ≥ 60%. Patients must not be on high doses of steroids or have active infections, uncontrolled HIV/hepatitis B/C, certain heart conditions, autoimmune diseases requiring systemic treatment in the past 2 years (except under specific conditions), or a history of allergic reactions to similar drugs.

What is being tested?

The study tests combining retifanlimab with radiation therapy and bevacizumab with/without epacadostat in treating recurrent brain tumors. It aims to enhance anti-tumor immune response and improve survival by leveraging the synergy between radiation therapy and immune modulators.

What are the potential side effects?

Potential side effects include inflammation in organs like the bowel or lungs (immune colitis/pneumonitis), infusion reactions from drug administration, increased risk of infection due to immune system suppression, blood clots if using anticoagulants concurrently with regimen B treatments, fatigue, digestive issues that may affect drug absorption.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My brain tumor is a high-grade glioblastoma or gliosarcoma.

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I am 18 years old or older.

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I can care for myself but may need occasional help.

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My cancer has come back and I can be treated again with radiation and bevacizumab.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am receiving treatment for an autoimmune disease.

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I do not have uncontrolled HIV or active hepatitis B or C.

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I do not have any uncontrolled illnesses, including serious heart conditions.

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I am taking more than 4 mg of dexamethasone daily.

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I have been treated with specific inhibitors before.

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I am not taking any medications or substances that are not allowed in regimen B.

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I have an abnormal heart rhythm, issues with my digestive system affecting medication absorption, or recently received a live vaccine.

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I am currently pregnant or breastfeeding.

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I have received a transplant from another person.

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I do not have severe immune or psychiatric conditions.

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I am currently on IV antibiotics for an infection or have active tuberculosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through 2 years after completion of treatment (estimated to be 4 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through 2 years after completion of treatment (estimated to be 4 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and through 2 years after completion of treatment (estimated to be 4 years) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall survival

Secondary study objectives

Neurologic functions as measured by the NANO scale

Progression-free survival (PFS)

Safety and toxicity of regimen as measured by adverse events experienced by participant

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Regimen B: Retifanlimab+RT+bevacizumab+epacadostatExperimental Treatment5 Interventions

* Retifanlimab will be given intravenously over the course of 30 to 60 minutes at a dose of 500 mg on Day 1 of each 28-day cycle. * Bevacizumab will be given intravenously at a dose of 10 mg/kg on Days 1 and 15 of each 28-day cycle. * Ten fractions of radiation therapy will be given at a dose of 3.5 Gy per fraction * Retifanlimab and bevacizumab will be started approximately two weeks before the first day of radiation therapy * Epacadostat will be administered orally at 400 mg BID. * Treatment may continue for up to two years.

Group II: Regimen A: Retifanlimab+RT+bevacizumabExperimental Treatment4 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Epacadostat

2018

Completed Phase 3

~1210

Radiation therapy

2013

Completed Phase 3

~2850

Retifanlimab

2018

Completed Phase 2

~430

Bevacizumab

2013

Completed Phase 4

~5540

Peripheral blood draw

2017

Completed Phase 2

~130

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for brain tumors include immunotherapy, radiation therapy, and targeted biological agents. Retifanlimab, an anti-PD-1 antibody, works by blocking the PD-1 pathway, thereby enhancing the immune system's ability to attack tumor cells. Radiation therapy uses high-energy radiation to damage the DNA of cancer cells, leading to cell death and tumor shrinkage. Bevacizumab, an anti-VEGF antibody, inhibits vascular endothelial growth factor (VEGF), reducing the tumor's blood supply and limiting its growth. Epacadostat, an IDO1 inhibitor, blocks the enzyme indoleamine 2,3-dioxygenase 1 (IDO1), which tumors use to evade the immune system. These treatments are crucial for brain tumor patients as they offer multiple strategies to target and reduce tumor growth, potentially improving survival and quality of life.

Changing paradigms for targeted therapies against diffuse infiltrative gliomas: tackling a moving target.