Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma

Recruiting in Palo Alto (17 mi)

Overseen byJiayi Huang, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Washington University School of Medicine

Stay on Your Current Meds

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

Meningioma is the most common central nervous system (CNS) tumor and accounts for approximately 30% of all CNS tumors. For meningioma recurring after surgery and radiation therapy, there is no effective medical therapy. Repeat surgery or radiation therapy may be possible, but they are temporizing measures with limited durable relief. PD-L1 expression in meningioma is increased for recurrent tumors or prior radiation therapy, and a recent case study reported significant reduction of an intracranial meningioma after 6 months of PD-L1 blockade. Radiation has been shown to augment immune response when combined with PD-L1 blockade. Proton radiation therapy has higher relative biological effectiveness (RBE) and may further amplify the above immunological signals. Combination of proton radiation therapy administered concurrently with PD-L1 inhibitor may maximize immune response for recurrent meningioma. However, confirmation of the increased immunogenicity or increased tumor infiltrating lymphocytes using the combination of radiation therapy and PD-L1 blockade have not been confirmed in patients. The proposed study will be a single institution, single-arm, open-label, phase Ib study to combine neoadjuvant avelumab (a PD-L1 inhibitor) with hypofractionated proton therapy of 20 CGE (cobalt gray equivalent) over 5 fractions followed by planned surgery for recurrent radiation-refractory meningioma. This study is designed to provide proof of concept to demonstrate on-target effect of the combination to increase immunogenicity by directly examining the resected tumor for immune response and to evaluate preliminary clinical efficacy

Eligibility Criteria

Inclusion Criteria

Karnofsky performance status (KPS) ≥ 60.

Hemoglobin ≥ 9 g/dL but transfusion allowed

You have received radiation treatment in the past, either through external beam radiation or radiosurgery, or a combination of both.

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Exclusion Criteria

You are currently taking part in another study testing an experimental medication.

You have serious medical conditions such as immune colitis, inflammatory bowel disease, immune pneumonitis or psychiatric conditions like suicidal thoughts or behaviors. Additionally, if you have any laboratory abnormalities that may increase the risk of participating in the study or interfere with the study's results. The investigator will determine if you are appropriate for entry into the study.

Previous treatment with PD-1 or PD-L1 directed therapy.

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Treatment Details

Interventions

Avelumab (PD-L1 Inhibitor)
Proton Therapy (Proton Beam Therapy)
Surgery (Procedure)

Participant Groups

1Treatment groups

Experimental Treatment

Group I: Avelumab + Proton TherapyExperimental Treatment3 Interventions

* Avelumab will be started concurrently with proton therapy (up to 3 days before or after is permissible) and administered every 2 weeks for 3 months * Proton therapy 20 CGE (cobalt gray equivalent) will be given over 5 daily fractions of 4 CGE per day during weekdays * After 3 months of avelumab, patient will have a brain MRI evaluation, and radiological response will be assigned based on the iRANO criteria. Surgery will be performed as per routine clinical care * If the brain MRI after 3 months of avelumab shows complete response with no signs of residual tumor, no surgery will be indicated, and the patient may continue to take adjuvant avelumab for an additional 3 months. * After the patient has recovered from the surgery and if deemed medically eligible by the treating physician to receive additional immunotherapy, avelumab will be restarted and administered every 2 weeks for an additional 3 months

Avelumab is already approved in European Union, United States, Japan for the following indications:

🇪🇺 Approved in European Union as Bavencio for: