Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03267836|
Recruitment Status : Recruiting
First Posted : August 30, 2017
Last Update Posted : December 11, 2018
|Condition or disease||Intervention/treatment||Phase|
|Meningioma Meningioma, Adult||Drug: Avelumab Radiation: Proton Therapy Procedure: Surgery||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 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 :||July 31, 2020|
|Estimated Study Completion Date :||July 31, 2020|
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 2 years after start of treatment) ]-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: 30 days after completion of treatment (estimated to be 7 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 ]
- 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 ]-Median OS and their 95% confidence intervals will be assessed using Kaplan-Meier product limit methods.
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
|Contact: Jiayi Huang, M.D.||firstname.lastname@example.org|
|United States, Missouri|
|Washington University School of Medicine||Recruiting|
|Saint Louis, Missouri, United States, 63110|
|Contact: Jiayi Huang, M.D. 314-362-8567 email@example.com|
|Principal Investigator: Jiayi Huang, M.D.|
|Sub-Investigator: Jian Campian, M.D., Ph.D.|
|Sub-Investigator: Michael Chicoine, M.D.|
|Sub-Investigator: Gavin Dunn, M.D., Ph.D.|
|Sub-Investigator: Albert Kim, M.D., Ph.D.|
|Sub-Investigator: Clifford Robinson, M.D.|
|Sub-Investigator: Xiaowei Wang, Ph.D.|
|Sub-Investigator: George Ansstas, M.D.|
|Sub-Investigator: Milan Chheda, M.D., Ph.D.|
|Sub-Investigator: Tanner Johanns, M.D., Ph.D.|
|Sub-Investigator: Ting Wang, Ph.D.|
|Sub-Investigator: Marco Colonna, M.D.|
|Sub-Investigator: Marina Cella, M.D.|
|Sub-Investigator: Leping Wan, M.P.H.|
|Principal Investigator:||Jiayi Huang, M.D.||Washington University School of Medicine|