Symptoms and General Pathology

All Conditions

Neoplasms

Nervous System Diseases

Rare Diseases

Recurrence

Meningioma

Disease Attributes

Neoplasms, Nerve Tissue

Neoplasms by Histologic Type

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Immunomodulating Agents

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants with recurrent grade II or III meningioma will receive stereotactic radiosurgery. in conjunction with pembrolizumab 200mg IV infusion on day 1 (to -1) of radiation and then every 3 weeks. Participants may be eligible for up to 17 additional cycles of pembrolizumab depending on disease status after completion of first course.

200mg given intravenously (IV) on day 1 (to -1) of radiation and then every 3 weeks until progression or unacceptable toxicity

Given in (a) single session treatment with margin dose of 15-20 Gy to the target for a maximum target volume of 8 cc or (b) five consecutive business days treatment to total dose of 25-30 Gy to the target for a maximum target volume of 20 cc when the target volume exceeds 8 cc or the target is in proximity to critical structures

Stereotactic Radiosurgery

Neuro-Oncology New Patient Coordinator

Nancy Oberheim Bush, MD, PhD

Steve Braunstein, MD

This phase II trial studies the effect of stereotactic radiosurgery and pembrolizumab in treating patients with meningioma that has come back (recurrent). Stereotactic radiosurgery is a type of external radiation therapy that uses special equipment to position the patient and precisely give a single large dose of radiation to a tumor. It is used to treat brain tumors and other brain disorders that cannot be treated by regular surgery. Pembrolizumab is a humanized monoclonal antibody. An antibody is a common type of protein made in the body in response to a foreign substance. Antibodies attack foreign substances and protect against infection. Antibodies can also be produced in the laboratory for use in treating patients; an antibody that is made in the lab is also known as a humanized monoclonal antibody. Pembrolizumab is a highly selective humanized monoclonal antibody that is designed to block the action of the receptor PD-1. It has been studied in lab experiments and in other types of cancer. The PD-1 receptor works to keep the immune system from noticing tumor cells. The addition of pembrolizumab to stereotactic radiosurgery may improve the progression free survival of patients with meningioma.

PRIMARY OBJECTIVE:

I. To determine the efficacy of stereotactic radiation and pembrolizumab for treatment of recurrent meningioma compared to historical control based on progression free survival at 12 months (PFS12).

SECONDARY OBJECTIVE:

I. To assess overall survival and further assess progression free survival of stereotactic radiation and pembrolizumab for treatment of recurrent meningioma.

EXPLORATORY OBJECTIVES:

I. To assess immune-related tumor effects pembrolizumab treatment in meningioma using magnetic resonance (MR) imaging in conjunction with assessment by Response Assessment in Neuro-Oncology Criteria (RANO) and Immunotherapy (i)RANO criteria.

II. To assess neurocognitive function and quality of life with pembrolizumab and radiation using the Neurologic Assessment in Neuro-Oncology (NANO) Scale, and European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire brain tumour module (QLQ-BN20).

III. To assess safety of the combined treatment modalities in meningioma, through evaluation of grade III adverse events (AEs) and dose-limiting toxicity (DLT).

OUTLINE:

Within -3 to 0 days from the start of stereotactic radiation therapy, patients receive pembrolizumab intravenously (IV) over 30 minutes on days 1 and 22. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo stereotactic radiosurgery on day 1 or days 1-5 of cycle 1 in the absence of disease progression or unacceptable toxicity.

All participants who have completed the first course, or stopped for complete response, may be eligible for up to an additional 17 cycles of pembrolizumab if there is investigator-determined progressive disease by iRANO after initial treatment.

After completion of study treatment, patients are followed up at 30 days, every 12 weeks for 2 years, and then every 6 months thereafter for up to 5 years.

Stereotactic Radiosurgery and Immunotherapy (Pembrolizumab) for the Treatment of Recurrent Meningioma

A Phase II Study of Stereotactic Radiosurgery in Conjunction With the PD-1 Inhibitor, Pembrolizumab for the Treatment of Recurrent Meningioma

Percentage of patients who are progression-free at the landmark of 12 months from start of treatment based on the target lesion(s) that are receiving radiation treatment will be reported. Tumor progression will be assessed using Immunotherapy Radiologic Assessment in Neuro-oncology Criteria (iRANO) and defined as \> 25% increase in sum of the products of perpendicular diameters of enhancing lesions (over baseline if no decrease) on stable or increasing doses of corticosteroids and/or a significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events.

Overall survival (OS) is defined as the duration of time from start of treatment to time of death estimated from the Kaplan-Meier method.

PFS is defined as the duration of time from start of treatment to time of progression using Immunotherapy Radiologic Assessment in Neuro-oncology Criteria (iRANO) or death estimated from the Kaplan-Meier method, and two-sided 95% confidence intervals (CI) will be computed based on the Greenwood's formula.

Spots Global Cancer Trial Database for grade i meningioma, adult