A Trial of Pembrolizumab for Refractory Atypical and Anaplastic Meningioma

NCT03016091 | Terminated Phase 2 Results

• 1 other identifier: MK-3475-415
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase II, Open-label, Single Arm Trial of Pembrolizumab for Refractory Atypical and Anaplastic Meningioma

Conditions

Atypical Meningioma; Anaplastic Meningioma; Hemangiopericytoma

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS)

  6 months PFS refers to the percentage of patients in a study who remain alive and whose disease has not worsened 6 months after starting treatment. To determine the 6 months PFS rate for patients with recurrent or progressive meningioma on pembrolizumab therapy we used the RANO meningioma criteria. The Response Assessment in Neuro-Oncology meningioma criteria are guidelines used to evaluate treatment response in meningioma patients, incorporating both radiological and clinical factors. Tumor response is classified into categories such as: complete response (CR), where the tumor disappears. Partial response (PR) with a 50% or more reduction in tumor size. Minor response (MR) between 25% to 50% reduction in tumor size. Stable disease (SD) indicating minimal change, and progressive disease (PD) defined by at least a 25% increase in tumor size, new lesions, or worsening clinical symptoms. these criteria emphasize the use of consistent imaging techniques such as MRI.

  6 months after starting treatment

• Progression Free Survival (PFS)

  12 months PFS refers to the percentage of patients in a study who remain alive and whose disease has not worsened 12 months after starting treatment. To determine the 12 months PFS rate for patients with recurrent or progressive meningioma on pembrolizumab therapy we used the RANO meningioma criteria. The Response Assessment in Neuro-Oncology meningioma criteria are guidelines used to evaluate treatment response in meningioma patients, incorporating both radiological and clinical factors. Tumor response is classified into categories such as: complete response (CR), where the tumor disappears. Partial response (PR) with a 50% or more reduction in tumor size. Minor response (MR) between 25% to 50% reduction in tumor size. Stable disease (SD) indicating minimal change, and progressive disease (PD) defined by at least a 25% increase in tumor size, new lesions, or worsening clinical symptoms. these criteria emphasize the use of consistent imaging techniques such as MRI.

  12 months after starting treatment

Secondary Outcomes (2)

• Overall Survival (OS)

  from date of diagnosis until date of death from any cause

• Overall Progression Free Survival (PFS)

  From the initiation of treatment to the occurrence of disease progression or death.

Study Arms (1)

Arm 1

EXPERIMENTAL

IV Pembrolizumab 200mg, given every 3 weeks until disease progression or intolerable toxicity

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

anti PD-L1

Arm 1

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Be 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Histologically, previously proven, grade II or III meningioma, HPC or classic radiographic features of a recurrent surgically inaccessible atypical or anaplastic meningioma.
• All patients would have to have recurrence despite radiotherapy, unless radiotherapy is contraindicated.
• No limit on the number of prior surgeries, radiation or radiosurgery treatments.
• No limit on prior systemic therapies - chemotherapy or biological agents.
• Patients who received stereotactic radiosurgery (SRS) are eligible without histologic documentation of recurrence if at least 6 months have passed from previous SRS treatment, and preferably, but not necessarily a 2-fluoro-2-deoxy-D-glucose PET imaging demonstrated hypermetabolism.
• KPS≥50%
• At least 4 weeks since any prior therapy.
• Life expectancy of at least 4 months.
• Dexamethasone use will be allowed up to a dose of 2mg per day. Steroids dose should be reduced or stopped 7 days prior to treatment with study drug.
• Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
• Table 1 Adequate Organ Function Laboratory Values
• Hematological Absolute neutrophil count (ANC)≥1,500 /mcL Platelets≥100,000 / mcL Hemoglobin≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment) Renal Serum creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl)≤1.5 X upper limit of normal (ULN) OR

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Patients who are steroid dependent and cannot reduce the dexamethasone dose to a maximal dose of 2mg per day.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent.
• Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• 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.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• 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.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

Sponsors & Collaborators

• Rabin Medical Center: lead

Study Sites (2)

Rabin Medical Center

Petah Tikva, Israel

Location

Tel Aviv Medical Center

Tel Aviv, Israel

Location

MeSH Terms

Conditions

Meningioma; Hemangiopericytoma

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

Limitations and Caveats

Twenty-five patients were required for the analysis to have 80% power to detect improvement in PFS-6 from 5% to 25% with a significance level of 0.05, and accounting for a 10% drop-out rate. The study was terminated after accrual of 18 patients, due to slow accrual and lack of efficacy

Results Point of Contact

• Title: Shlomit Yust-Katz MD
• Organization: Davidoff Cancer Center at Rabin Medical Center

shlomit2@clalit.org.il

92739378002

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: December 22, 2016
• First Posted: January 10, 2017
• Study Start: January 1, 2018
• Primary Completion: July 1, 2022
• Study Completion: December 1, 2022
• Last Updated: February 18, 2025
• Results First Posted: January 22, 2025

Record last verified: 2018-01

Locations

IL (2)