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Phase II Trial of Pembrolizumab in Recurrent or Residual High Grade 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: NCT03279692
Recruitment Status : Recruiting
First Posted : September 12, 2017
Last Update Posted : September 7, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Priscilla Brastianos, Massachusetts General Hospital

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


Condition or disease Intervention/treatment Phase
High Grade Meningioma Drug: Pembrolizumab Phase 2

Detailed Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved pembrolizumab for this specific disease but it has been approved for other uses.

In this research study, the investigators are studying pembrolizumab in participants with meningioma. Research studies have shown that meningioma tumor cells express a gene called PD-L1. The investigators will be looking to determine whether the study drug may may stop meningioma tumors from growing.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Pembrolizumab in Recurrent or Residual High Grade Meningioma
Actual Study Start Date : November 7, 2017
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : September 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab
  • Pembrolizumab will be administered every 3 weeks
  • Pembrolizumab will be administered through IV infusion
Drug: Pembrolizumab
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
Other Name: Keytruda




Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: Every 6 weeks, up to 6 months ]
    Contrast-enhanced cranial MRI will be performed every 6 weeks. PFS6 is defined as not having progressive disease or death within six months of the first day of treatment. Contrast-enhanced cranial magnetic resonance imaging (MRI) will be performed every 6 weeks.


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 3 months and 6 months ]
    The distributions of overall survival will be summarized using the method of Kaplan-Meier. The follow-up of patients who are alive at the time of analysis will be censored at the date of last assessment of vital status. Median OS will be presented and accompanied by 90% confidence intervals estimated using log(-log(survival)) methodology. Survival point estimates at 3 and 6 months will also be presented with confidence intervals.

  2. Toxicity [ Time Frame: Baseline to 21 days ]
    All adverse events recorded during the trial will be summarized for all patients having received one or more doses of pembrolizumab. The proportions of patients with grade-3 or higher hematologic toxicities or grade-3 or higher neurologic toxicities will be presented with 90% exact binomial confidence intervals.

  3. Intracranial response [ Time Frame: 6 months ]
    The proportion of patients with intracranial response (CR, PR or SD by RANO) will be presented with a two-sided, 90% exact binomial confidence interval.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

-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
  • Recovered to CTCAE grade 1 or less toxicity from other agents with exception of alopecia and fatigue.
  • No craniotomy within 28 days of registration.

    • Not pregnant and not nursing:
    • A female of childbearing potential is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.
    • Age ≥ 18 years
    • ECOG Performance Status < 2
    • Patient history: Patients with history of NF may have other stable CNS tumors (schwannoma, acoustic neuroma or ependymoma) if lesions have been stable for 6 months.
    • Metastatic meningiomas (as defined by extracranial meningiomas) and meningioma with extra-cranial spread are allowed.
    • Required Initial Laboratory Values
    • Participants must have normal organ and marrow function as defined in Table 1, all screening labs should be performed within 14 days of treatment initiation.
    • Required Initial Laboratory Values
  • System Laboratory Value
  • 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

    ≥60 mL/min for subject with creatinine levels > 1.5 X institutional ULN

  • Hepatic
  • Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN
  • Albumin >2.5 mg/dL
  • Coagulation
  • International Normalized Ratio (INR) or Prothrombin Time (PT)
  • Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

    ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

  • Creatinine clearance should be calculated per institutional standard.

    • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
    • Ability to understand and the willingness to sign a written informed consent document.
    • Stable dose of dexamethasone 2mg or less for 7 days prior to initiation of treatment

Exclusion Criteria:

  • 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.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). HIV-positive participants on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab. In addition, these participants are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated.
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Unable to undergo brain MRI.

Information from the National Library of Medicine

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): NCT03279692


Contacts
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Contact: Nicola Gribbin 617-726-9579 NGRIBBIN@PARTNERS.ORG

Locations
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United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Eudocia Lee, MD    617-632-2166      
Principal Investigator: Eudocia Lee, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02214
Contact: Priscilla K Brastianos, MD    617-724-8770    pbrastianos@mgh.harvard.edu   
Principal Investigator: Priscilla Brastianos, MD         
Sponsors and Collaborators
Massachusetts General Hospital
Merck Sharp & Dohme Corp.
Investigators
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Principal Investigator: Priscilla Brastianos, MD Massachusetts General Hospital
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Responsible Party: Priscilla Brastianos, Principal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03279692    
Other Study ID Numbers: 17-296
First Posted: September 12, 2017    Key Record Dates
Last Update Posted: September 7, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Priscilla Brastianos, Massachusetts General Hospital:
Meningioma
Additional relevant MeSH terms:
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Meningioma
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
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents