What side effects are associated with this type of intervention?

Common treatments for Glioblastoma include Carmustine Wafers, Radiation Therapy, Retifanlimab, and Temozolomide. Carmustine Wafers can cause local side effects such as brain edema and infection. Radiation Therapy may lead to acute and subacute radiation encephalopathy, manifesting as headaches, focal neurologic symptoms, and nausea. Retifanlimab, a PD-1 inhibitor, can enhance immune response but may cause immune-related adverse effects like colitis, pneumonitis, and hepatitis. Temozolomide, a DNA-damaging chemotherapy, is associated with headaches, nausea, vomiting, and potential impacts on reproductive function.

What prior FDA approvals exist?

The FDA has approved several treatments for Glioblastoma that align with those being studied in the trial. Carmustine wafers (Gliadel) are approved for local chemotherapy, providing direct delivery of the drug to the tumor site. Radiation therapy is a standard treatment that uses high-energy rays to kill cancer cells. Temozolomide (Temodar) is an oral chemotherapy agent that damages DNA in cancer cells, making it harder for them to repair and multiply. While retifanlimab, a PD-1 inhibitor, is not specifically mentioned as FDA-approved for Glioblastoma, similar PD-1 inhibitors like nivolumab (Opdivo) have been explored in clinical trials for their potential to enhance the immune response against cancer cells.

What other types of research exist?

Promising novel alternatives for Glioblastoma treatment in 2024 include: 1) Bevacizumab (anti-angiogenic therapy) combined with other agents like lomustine, 2) Laser Interstitial Thermal Therapy (LITT) for targeted tumor ablation, 3) Checkpoint inhibitors such as nivolumab and pembrolizumab, especially in combination with other treatments, 4) Targeted therapies like BRAF inhibitors (e.g., trametinib) for specific genetic mutations, and 5) Investigational agents like emactuzumab (CSF1R inhibitor) and other monoclonal antibodies targeting tumor-specific pathways.

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Carmustine + Retifanlimab + Radiation for Glioblastoma

Phase 1

Recruiting

Led By Lawrence Kleinberg, MD

Research Sponsored by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Eligibility Criteria Checklist

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

Must have

Age ≥18 years

Karnofsky Performance Status of ≥ 60

Must not have

Central nervous system hemorrhage of Grade > 1 on baseline MRI scan, unless subsequently documented to have resolved

Active infection requiring systemic antibiotics or antifungal treatment

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of treatments including carmustine wafers, radiation, retifanlimab, and possibly temozolomide in adults newly diagnosed with glioblastoma multiforme. The goal is to see if these treatments are safe and help patients live longer. The treatments work by directly targeting the tumor, damaging cancer cells' DNA, and boosting the immune system to fight the cancer. Carmustine wafers have been shown to be an effective addition to standard treatment in glioblastoma, with a significant survival benefit.

Who is the study for?

Adults over 18 with newly-diagnosed Grade IV Glioblastoma who've had carmustine wafers placed during surgery. They haven't had other GBM treatments, can sign consent, and are on stable or decreasing steroids. Women must not be pregnant or nursing, and men must use effective contraception. Participants need normal organ/marrow function, a Karnofsky Performance Status of ≥60, and no prior malignancies within 3 years (with some exceptions).

What is being tested?

The trial is testing the combination of carmustine wafers with radiation therapy and retifanlimab immunotherapy, with or without temozolomide chemotherapy in adults after surgical placement of carmustine for glioblastoma treatment. The goal is to assess safety and survival outcomes.

What are the potential side effects?

Possible side effects include reactions at the infusion site from retifanlimab, fatigue from radiation therapy or chemotherapy, digestive issues like nausea from temozolomide, blood disorders such as low white cell counts increasing infection risk, and potential liver or kidney function changes.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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I can care for myself but may not be able to do active work.

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My organ and bone marrow functions are normal.

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I have a new diagnosis of Grade IV brain cancer and had treatment with carmustine wafers.

Exclusion Criteria

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

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I had a brain bleed greater than Grade 1, but it's now resolved.

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I am currently on antibiotics or antifungal treatment for an infection.

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I have a brain condition not related to my cancer.

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I am taking high doses of steroids for an autoimmune disease.

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I have been treated with drugs that target the immune system.

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I haven't had any cancer except for certain types in the last 3 years.

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I have an autoimmune disease, but it's not one of the exceptions listed.

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I am allergic to retifanlimab or its ingredients.

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I have had an organ transplant.

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I have not had surgery within the last week.

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I cannot take pills by mouth or have a stomach condition affecting medication absorption.

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My side effects from previous treatments have mostly gone away.

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I have or had lung scarring or inflammation not caused by an infection.

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My cancer has spread outside of my brain.

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I have experienced severe side effects from previous treatments.

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My brain tumor has come back or gotten worse.

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I do not have any unmanaged ongoing illnesses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 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

Feasibility of combination retifanlimab and radiation with and without temozolomide as assessed by number of participants who experience adverse events

Maximum Tolerated Dose (MTD) as determined by number of participants with dose limiting toxicities (DLT)

Safety of combination retifanlimab and radiation with and without temozolomide as assessed by number of participants who experience adverse events

Secondary study objectives

Overall Response Rate

Overall Survival

Progression Free Survival

+1 more

Other study objectives

B cell count

Biomarker assessment in tumor and blood samples

CD4 cell count

+9 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Arm C- Radiation Therapy and TemozolomideExperimental Treatment2 Interventions

Participants will receive Radiation Therapy and Temozolomide which is the Standard of Care.

Group II: Arm B- Retifanlimab, Radiation Therapy and TemozolomideExperimental Treatment3 Interventions

Participants will receive Retifanlimab, Radiation Therapy and Temozolomide.

Group III: Arm A- Retifanlimab and Radiation TherapyExperimental Treatment2 Interventions

Participants will receive Retifanlimab and Radiation Therapy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Retifanlimab

2018

Completed Phase 2

~430

Temozolomide

2010

Completed Phase 3

~1880

Radiation Therapy

2017

Completed Phase 3

~7250

0 / 21Eligibility 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

Glioblastoma treatments employ various mechanisms to target cancer cells. Carmustine wafers deliver localized chemotherapy directly to the tumor site, minimizing systemic side effects. Radiation therapy uses high-energy rays to damage the DNA of cancer cells, leading to cell death. Retifanlimab, a PD-1 inhibitor, enhances the immune system's ability to recognize and attack cancer cells. Temozolomide is an oral chemotherapy that damages the DNA of cancer cells, preventing their replication. These diverse mechanisms are essential for Glioblastoma patients as they provide a multifaceted approach to tackling the tumor, potentially improving treatment efficacy and patient outcomes.