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

NCT04659811 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 19109NCI-2020-11359
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Grade I Meningioma, Adult; Grade II Meningioma, Adult; Grade III Meningioma, Adult; Recurrent Meningioma

Keywords

PD-1 Inhibitor; Stereotactic Radiosurgery; Immunotherapy; Pembrolizumab

Outcome Measures

Primary Outcomes (1)

• Percentage of participants with Progression Free Survival at 12 months (PFS12)

  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.

  Up to 12 months

Secondary Outcomes (2)

• Median overall survival (OS)

  Up to 5 years

• Median progression free survival (PFS)

  Up to 5 years

Study Arms (1)

Treatment for recurrent meningioma (pembrolizumab, stereotactic radiosurgery)

EXPERIMENTAL

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.

Drug: Pembrolizumab; Procedure: Stereotactic Radiosurgery

Interventions

Pembrolizumab DRUG

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

Also known as: Keytruda, Pembrolizumab IV

Treatment for recurrent meningioma (pembrolizumab, stereotactic radiosurgery)

Stereotactic Radiosurgery PROCEDURE

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

Also known as: SRS

Treatment for recurrent meningioma (pembrolizumab, stereotactic radiosurgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed World Health Organization (WHO) grade II or III meningioma that is progressive or with one or more recurrences following surgical resection and radiotherapy
• Patients must be eligible/appropriate for treatment with radiation therapy, specifically, if radiation is given in a single session, the target volume cannot exceed 8 ccs or if given in five (consecutive business days) sessions, the target volume cannot exceed 20 ccs
• Prior therapy:
• There is no limit on the number of prior surgeries or systemically administered therapeutic agents
• An interval of \>= 28 days and full recovery (no ongoing safety issues) from surgical resection
• An interval of \> 7 days from stereotactic biopsy
• For prior systemic agents, participants must be at least 4 weeks (or 5 half-lives, whichever is shorter) from other prior cytotoxic chemotherapy (6 weeks from nitrosoureas) or biologic therapies
• Be \>= 18 years of age on day of signing informed consent
• Have a Karnofsky performance status (KPS) \>= 70
• Absolute neutrophil count (ANC) \>= 1500/microliter (uL) (within 28 days prior to enrollment)
• Platelets \>= 100000/uL (within 28 days prior to enrollment)
• Hemoglobin \>= 9.0 g/dL or \>= 5.6 mmol/L (within 28 days prior to enrollment)
• \* Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
• Creatinine =\< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance \>= 30 mL/min for participant with creatinine levels \> 1.5 x institutional ULN (within 28 days prior to enrollment) (glomerular filtration rate (GFR) can also be used in place of creatinine or creatinine clearance (CrCl))
• \* Creatinine clearance (CrCl) should be calculated per institutional standard

You may not qualify if:

• WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
• Tumors that are primarily localized to the brainstem or spinal cord, NOTE: patients with known tumors in these areas that are not progressive are not excluded
• Known metastasis outside if the central nervous system (CNS), however, no baseline staging is required
• Evidence of intratumoral or peritumoral hemorrhage on baseline MRI scan other than those that are grade =\< 1 and either post-operative or stable on at least 2 consecutive MRI scans
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137)
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
• Prior treatment with systemic immunosuppressive treatments, such as methotrexate, chloroquine, azathioprine, etc. within 3 months of start of study therapy
• No concurrent treatment on another clinical trial for 4 weeks (or 5 half-lives, whichever is shorter) for prior systemic agents, other prior cytotoxic chemotherapy (6 weeks from nitrosoureas) or biologic therapies. Supportive care trials or non- treatment trials, e.g. quality of life, are allowed
• Has severe hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. Steroids for cerebral edema are allowed if less than or equal to 2 mg of dexamethasone
• Has an active infection requiring systemic therapy
• Has a known history of human immunodeficiency virus (HIV) (testing not required)

Sponsors & Collaborators

• Nancy Ann Oberheim Bush, MD: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Meningioma

Interventions

pembrolizumab; Radiosurgery

Condition Hierarchy (Ancestors)

Neoplasms, Nerve Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Nancy Oberheim Bush, MD, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Steve Braunstein, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 30, 2020
• First Posted: December 9, 2020
• Study Start: March 25, 2021
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2031
• Last Updated: April 15, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)