134 Participants Needed

Retifanlimab + Bevacizumab + Radiation for Recurrent Glioblastoma

Recruiting at 2 trial locations
IM
MC
SB
AM
Overseen ByAndrea McMahon
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Academic and Community Cancer Research United
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This phase II trial tests how well retifanlimab with bevacizumab and hypofractionated radiotherapy, compared to bevacizumab and hypofractionated radiotherapy alone, works in treating patients with glioblastoma that has come back after a period of improvement (recurrent). A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as retifanlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving retifanlimab with bevacizumab and hypofractionated radiotherapy may work better in treating patients with recurrent glioblastoma than bevacizumab and hypofractionated radiotherapy alone.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on certain investigational agents or treatments for autoimmune diseases, you may need to stop them before joining the trial. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment Retifanlimab + Bevacizumab + Radiation for Recurrent Glioblastoma?

Research suggests that combining bevacizumab (a drug that blocks blood vessel growth) with radiation can improve survival in patients with recurrent glioblastoma, a type of brain cancer. Bevacizumab has been approved for use in recurrent glioblastoma and has shown promise when used with radiation therapy.12345

Is the combination of Retifanlimab, Bevacizumab, and Radiation generally safe for humans?

Bevacizumab, when used with radiation and other treatments, has been linked to side effects like stroke, bleeding, and wound-healing issues, especially in brain tumors. However, studies show it is generally feasible and safe when combined with radiation for recurrent high-grade gliomas, though some expected side effects may occur.36789

What makes the drug combination of Retifanlimab, Bevacizumab, and Radiation unique for treating recurrent glioblastoma?

This treatment is unique because it combines Retifanlimab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with Bevacizumab, which prevents the growth of blood vessels that supply tumors, and radiation therapy, which directly targets and kills cancer cells. This multi-faceted approach aims to enhance the effectiveness of treatment for recurrent glioblastoma, a condition with limited standard treatment options.2351011

Research Team

JL

Jian L Campian

Principal Investigator

Academic and Community Cancer Research United

Eligibility Criteria

Adults over 18 with recurrent grade IV glioblastoma, who are candidates for radiotherapy and have a Karnofsky performance status of at least 60%. They must have adequate blood counts, organ function, and controlled steroid use. Pregnant or nursing individuals and those not using contraception are excluded. People with severe diseases or conditions that could interfere with the trial or pose risks are also ineligible.

Inclusion Criteria

Measurable disease or non-measurable disease per Response Assessment in Neuro-Oncology (RANO) criteria
I am a candidate for radiation treatment.
Absolute neutrophil count (ANC) ≥ 1,500/mm^3 (obtained ≤ 28 days prior to registration)
See 15 more

Exclusion Criteria

Co-morbid systemic illness or other severe concurrent disease which, in the judgement of the investigator, would make the patient inappropriate for entry into the study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
I haven't taken any experimental drugs for my cancer in the last 2 weeks.
I don't have an active, severe autoimmune disease needing strong medication in the last 2 years.
See 9 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive retifanlimab and bevacizumab with hypofractionated radiotherapy or bevacizumab with hypofractionated radiotherapy alone. Treatment repeats every 28 days for up to 2 years.

Up to 2 years
IV administration on day 1 and 15 of each cycle, daily radiotherapy for 10 treatments starting on day 15 of cycle 1

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes survival checks and adverse event monitoring.

4 years
Follow-up at 30 days post-treatment, then every 2 months for the first year, and every 6 months thereafter

Treatment Details

Interventions

  • Bevacizumab
  • Hypofractionated Radiation Therapy
  • Retifanlimab
Trial OverviewThe trial is testing retifanlimab combined with bevacizumab and hypofractionated radiotherapy versus just bevacizumab and hypofractionated radiotherapy in treating recurrent glioblastoma. Retifanlimab is an immunotherapy drug that may help the immune system fight cancer; bevacizumab aims to stop tumor growth by inhibiting blood vessel formation.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Arm B (Bevacizumab and radiation)Experimental Treatment6 Interventions
Patients receive bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT QD, starting in cycle 1 on day 15 for 10 treatments. Patients undergo MRI or CT, as well as blood sample collection throughout the study.
Group II: Arm A (Retifanlimab, bevacizumab and HFRT)Experimental Treatment7 Interventions
ARM I: Patients receive retifanlimab IV over 30 minutes on day 1 and bevacizumab IV on day 1 and 15 of each cycle. Treatment repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo HFRT QD, starting in cycle 1 on day 15 for 10 treatments. Patients undergo MRI or CT, as well as blood sample collection throughout the study.

Retifanlimab is already approved in United States for the following indications:

🇺🇸
Approved in United States as Zynyz for:
  • Merkel cell carcinoma

Find a Clinic Near You

Who Is Running the Clinical Trial?

Academic and Community Cancer Research United

Lead Sponsor

Trials
54
Recruited
4,900+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

In a study of 45 patients with glioblastoma (GBM) treated with gamma knife stereotactic radiosurgery (SRS) and bevacizumab, the combination showed promising results with a median overall survival of 13.3 months after treatment.
The treatment was found to be safe, with no radiation-related adverse events reported, and factors like Karnofsky Performance Score (KPS) and radiation dose significantly influenced progression-free survival (PFS).
Gamma Knife Stereotactic Radiosurgery in Combination with Bevacizumab for Recurrent Glioblastoma.Morris, SL., Zhu, P., Rao, M., et al.[2020]
Re-irradiation combined with bevacizumab and temozolomide is a safe and feasible treatment option for patients with bevacizumab-refractory high-grade glioma, showing a median overall survival of 8.5 months across 54 patients.
Patients who were more than 36 months from their initial radiation treatment experienced a significantly longer median overall survival of 13.3 months, suggesting that timing of re-irradiation may influence treatment efficacy.
A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas.Dixit, KS., Sachdev, S., Amidei, C., et al.[2022]
In a retrospective study of 14 heavily pretreated patients with recurrent high-grade gliomas, re-irradiation combined with bevacizumab showed a median progression-free survival of 5.1 months and a median overall survival of 9.0 months, indicating potential efficacy for this treatment approach.
The study found that re-irradiation with either conventional 3D-conformal or intensified modulated radiotherapy (IMRT) was feasible and generally safe, with only one case of radionecrosis detected and other side effects being typical of bevacizumab treatment.
Re-irradiation with and without bevacizumab as salvage therapy for recurrent or progressive high-grade gliomas.Hundsberger, T., Brügge, D., Putora, PM., et al.[2022]

References

Gamma Knife Stereotactic Radiosurgery in Combination with Bevacizumab for Recurrent Glioblastoma. [2020]
A multi-center prospective study of re-irradiation with bevacizumab and temozolomide in patients with bevacizumab refractory recurrent high-grade gliomas. [2022]
Re-irradiation with and without bevacizumab as salvage therapy for recurrent or progressive high-grade gliomas. [2022]
Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas. [2022]
Bevacizumab in recurrent glioblastoma: five informative patient scenarios. [2016]
Phase II pilot study of bevacizumab in combination with temozolomide and regional radiation therapy for up-front treatment of patients with newly diagnosed glioblastoma multiforme: interim analysis of safety and tolerability. [2022]
Bevacizumab, temozolomide, and radiotherapy for newly diagnosed glioblastoma: comprehensive safety results during and after first-line therapy. [2022]
Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143. [2023]
Phase II study of bevacizumab plus temozolomide during and after radiation therapy for patients with newly diagnosed glioblastoma multiforme. [2022]
Clinical Benefit of Bevacizumab and Irinotecan (BEV+IRI) in Patients With Relapsed/Refractory Glioblastoma (r/rGBM) and its Potential Predictors. [2022]
Re-irradiation of recurrent IDH-wildtype glioblastoma in the bevacizumab and immunotherapy era: Target delineation, outcomes and patterns of recurrence. [2023]