Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma
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|ClinicalTrials.gov Identifier: NCT03267836|
Recruitment Status : Active, not recruiting
First Posted : August 30, 2017
Last Update Posted : September 28, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Meningioma Meningioma, Adult||Drug: Avelumab Radiation: Proton Therapy Procedure: Surgery||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase Ib Study of Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma|
|Actual Study Start Date :||January 10, 2018|
|Estimated Primary Completion Date :||March 31, 2023|
|Estimated Study Completion Date :||September 30, 2025|
Experimental: Avelumab + Proton Therapy
Other Name: Bavencio
Radiation: Proton Therapy
-Proton therapy will start concurrently with the first dose of avelumab (up to 3 days before or after is permissible) and will be administered once daily during weekdays (Monday through Friday).
-Standard of care
- Immunogenicity as measured by changes of CD8+/CD4+ tumor infiltrating lymphocytes (TILs) in recurrent radiation-refractory meningioma [ Time Frame: Through time of progression (up to 6 months after completion of treatment - estimated to be 12 months) ]-The change of CD8+/CD4+ TILs in the tumor specimens over time will be compared using paired t-test or Wilcoxon rank-sum test as appropriate and plotted using the box plot. The association between TILs increase and clinical response will also be explored by comparing the differences in theses biomarkers between responders versus non-responders using t-test or Mann-Whitney rank-sum test as appropriate.
- Safety of proton therapy and avelumab in combination as measured by The number and percentage of subjects experiencing each type of adverse event will be tabulated by severity, and relationship to treatment. [ Time Frame: 6 months after completion of treatment (estimated to be 12 months) ]If appropriate, confidence intervals will be used to characterize the precision of the estimate.
- Radiological response [ Time Frame: 3 months of immunotherapy ]
- 95% confidence intervals will be calculated
- Response and progression will be evaluated in this study using the modified updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline
- Pathologic response [ Time Frame: 3 months of immunotherapy ]-Will be evaluated by board-certified neuropathologist on formalin-fixed paraffin-embedded tumor specimens stained with hematoxylin and eosin, where responders are defined as ≥30% necrosis/reactive changes and ≤50% viable tumor.
- Progression-free survival (PFS) [ Time Frame: Through 2 years after completion of treatment (estimated to be 2.5 years) ]
- PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
- Median PFS and their 95% confidence intervals will be assessed using Kaplan-Meier product limit methods.
- Overall survival (OS) [ Time Frame: Through 2 years after completion of treatment (estimated to be 2.5 years) ]-Median OS and their 95% confidence intervals will be assessed using Kaplan-Meier product limit methods.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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 × 10⁹ cells per L
- Platelet count ≥ 100 × 10⁹ 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)
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03267836
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|Principal Investigator:||Jiayi Huang, M.D.||Washington University School of Medicine|
|Responsible Party:||Washington University School of Medicine|
|Other Study ID Numbers:||
|First Posted:||August 30, 2017 Key Record Dates|
|Last Update Posted:||September 28, 2022|
|Last Verified:||September 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||Yes|
|Product Manufactured in and Exported from the U.S.:||Yes|
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