Phase II Trial of Pembrolizumab in Recurrent or Residual High Grade Meningioma

NCT03279692 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-296
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a drug as a possible treatment for High Grade Meningioma. The drug involved in this study is an immunotherapy drug called pembrolizumab

Conditions

High Grade Meningioma

Keywords

Meningioma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival at 6 Months (PFS6)

  Progression-free survival at 6 months is defined as not having disease progression per RANO (response assessment in neuro-oncology) criteria or death from any cause within six months of the first day of treatment with pembrolizumab. Contrast-enhanced cranial magnetic resonance imaging (MRI) was performed every 6 weeks to assess patient response to treatment. Progressive disease is defined per RANO criteria as the appearance of a new lesion, an increase in the size of a patient's existing lesions, or clear clinical worsening (seizures, medication side effects, complications of therapy, cerebrovascular events, infection, etc.)

  up to 6 months

Secondary Outcomes (5)

• Overall Survival (OS)

  Up to 35 months

• Overall Survival (OS) at 3 Months

  3 months

• Overall Survival (OS) at 6 Months

  6 months

• Percentage of Participants With Treatment-related Adverse Events

  Up to 26 months

• Number of Participants With Intracranial Response

  Up to 25 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

* Pembrolizumab will be administered every 3 weeks * Pembrolizumab will be administered through IV infusion

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells

Also known as: Keytruda

Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Documentation Of Disease
• Histologic Documentation: Histologically proven recurrent or residual intracranial or metastatic meningioma or meningioma with extracranial spread
• Progressive OR residual disease, as defined by the following:
• Progressive disease, as defined as an increase in size of the measurable primary lesion on imaging by 25% or more (bidirectional area). The change must occur between scans separated by no more than 24 months.
• Residual measurable disease: For Grade II or III meningioma, residual measurable disease immediately after surgery without requirement for progression. Residual measurable disease will be defined by bidimensionally measurable lesions with clearly defined margins by MRI scans, with a minimum diameter of 10mm in both dimensions.
• Post radiation patients: Patients with measurable and progressive meningioma who have received radiation are potentially eligible, but need to show evidence of progressive disease in the radiated field after completion of radiation. At least 24 weeks must have elapsed from completion of radiation to registration. Patients that have progressive disease outside of the radiation field do not need to wait 24 weeks from completion of radiation.
• Measurable Disease: Measurable disease is defined by a bidimensionally measurable main lesion on MRI or CT images (MRI preferred) with clearly defined margins and ≥ 10 mm. Multifocal disease is allowed as long as one lesion meets criteria for measurable disease and progressive disease.
• Prior Treatment
• Prior medical therapy is allowed but not required.
• Meningioma that have resulted from prior radiation therapy are allowed.
• No limit on number of prior therapies.
• No chemotherapy, other investigational agents within 14 days of study treatment.
• No other concurrent investigational agents or other meningioma-directed therapy (chemotherapy, radiation) while on study.
• For patients treated with external beam radiation, interstitial brachytherapy or radiosurgery, an interval \> 24 weeks must have elapsed from completion of XRT to registration.
• Stable dose of dexamethasone 2mg or less for 7 days prior to initiation of treatment

You may not qualify if:

• Participants who have had chemotherapy, targeted small molecule therapy or study therapy within 14 days of protocol treatment, or those who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 2 weeks earlier. Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study. If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Participants with brainstem lesions
• Participants who are receiving any other investigational agents.
• Participants who have a diagnosis of an immunodeficiency.
• Requires treatment with high dose systemic corticosteroids defined as dexamethasone \>2mg/day or bioequivalent within 7 days of initiating therapy.
• Has received systemic immunosuppressive treatments, aside from systemic corticosteroids as described in Section 5.7, within three months of start of study drug
• Hypersensitivity to pembrolizumab or any of its excipients
• Has a known history of active TB (Bacillus Tuberculosis)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer or stable NF-related neoplasms (Section 3.1.7).
• 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has known history of, or any evidence of active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• Massachusetts General Hospital: lead

Study Sites (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02214, United States

Location

Related Publications (1)

• Brastianos PK, Kim AE, Giobbie-Hurder A, Lee EQ, Wang N, Eichler AF, Chukwueke U, Forst DA, Arrillaga-Romany IC, Dietrich J, Corbin Z, Moliterno J, Baehring J, White M, Lou KW, Larson J, de Sauvage MA, Evancic K, Mora J, Nayyar N, Loeffler J, Oh K, Shih HA, Curry WT, Cahill DP, Barker FG, Gerstner ER, Santagata S. Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas. Nat Commun. 2022 Mar 14;13(1):1325. doi: 10.1038/s41467-022-29052-7.

  PMID: 35289329 DERIVED

MeSH Terms

Conditions

Meningioma

Interventions

pembrolizumab

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

Results Point of Contact

• Title: Priscilla Brastianos, MD
• Organization: Massachusetts General Hospital

pbrastianos@partners.org

617-724-8770

Study Officials

• Priscilla Brastianos, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: September 5, 2017
• First Posted: September 12, 2017
• Study Start: November 7, 2017
• Primary Completion: September 18, 2021
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 29, 2026
• Results First Posted: June 6, 2023

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)