Clinical Trials /

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

NCT03279692

Description:

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

Related Conditions:
  • Meningioma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Trial of Pembrolizumab in Recurrent or Residual High Grade Meningioma
  • Official Title: Phase II Trial of Pembrolizumab in Recurrent or Residual High Grade Meningioma

Clinical Trial IDs

  • ORG STUDY ID: 17-296
  • NCT ID: NCT03279692

Conditions

  • High Grade Meningioma

Interventions

DrugSynonymsArms
PembrolizumabKeytrudaPembrolizumab

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
PembrolizumabExperimentalPembrolizumab will be administered every 3 weeks Pembrolizumab will be administered through IV infusion
  • Pembrolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:Every 6 weeks, up to 6 months
Safety Issue:
Description: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

Measure:Overall Survival
Time Frame:3 months and 6 months
Safety Issue:
Description: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.
Measure:Toxicity
Time Frame:Baseline to 21 days
Safety Issue:
Description: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.
Measure:Intracranial response
Time Frame:6 months
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Massachusetts General Hospital

Trial Keywords

  • Meningioma

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