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

  • STATUS
    Recruiting
  • End date
    Sep 30, 2025
  • participants needed
    12
  • sponsor
    Washington University School of Medicine
Updated on 4 March 2022
platelet count
medical therapy
karnofsky performance status
dexamethasone
neutrophil count
blood transfusion
proton therapy
ebrt
central nervous system tumor
definitive radiation therapy
recurrent meningioma
intracranial meningioma

Summary

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

Details
Condition Meningioma, Meningioma, Adult
Treatment Surgery, Avelumab, proton therapy
Clinical Study IdentifierNCT03267836
SponsorWashington University School of Medicine
Last Modified on4 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Diagnosis of recurrent or progressive histologically confirmed WHO grade I-III meningioma which has failed maximal safe resection and radiation therapy
At least one prior surgery with available archival formalin-fixed paraffin-embedded (FFPE) tumor blocks. In the case that tumor block is unavailable, unstained tissue sections may be used in its place
Prior treatment must include external beam radiation, radiosurgery, or combination of both
Deemed eligible for additional partial resection by treating physician and determined to be safe to receive 3 months of neoadjuvant therapy before planned surgery
Age 18 years old. 6. Karnofsky performance status (KPS) 60
Adequate organ and bone marrow function (as defined by the following laboratory values)
Absolute neutrophil count 1.5 10 cells per L
Platelet count 100 10 platelets per L
Hemoglobin 9 g/dL but transfusion allowed
Total bilirubin concentration of 1.5 the upper limit of normal [ULN] range
Aspartate aminotransferase and alanine aminotransferase concentrations of 2.5 ULN)
Estimated creatinine clearance 30 mL/min according to the Cockcroft-Gault formula
Dexamethasone dose 4mg daily
Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in the study, she must inform her treating physician immediately
Able to understand and willing to sign an IRB approved written informed consent document (or legally authorized representative, if applicable)

Exclusion Criteria

Previous treatment with PD-1 or PD-L1 directed therapy
Active infection requiring systemic therapy
Uncontrolled intercurrent illness including, but not limited to, clinically significant (i.e. active) cardiovascular disease: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), congestive heart failure ( NYHA class II), unstable angina pectoris, or serious cardiac arrhythmia requiring medication
Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive)
Currently receiving any other investigational agents
Current use of immunosuppressive medication, EXCEPT for the following
Intranasal, inhaled, topical steroids, or local steroid injection (e.g. intra-articular injection)
Systemic corticosteroids at physiologic doses 10 mg/day of prednisone or equivalent
Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible
Prior organ transplantation including allogeneic stem cell transplantation
Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis, or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines
History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition to avelumab or other agents used in the study (or monoclonal antibodies)
Persisting toxicity related to prior therapy (CTCAE > grade 1); however, alopecia, sensory neuropathy grade 2, or other grade 2 not constituting a safety risk based on the investigator's judgment are acceptable
Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry
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