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Trial record 17 of 27 for:    dipg | Recruiting, Not yet recruiting, Available Studies

Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, or Hypermutated Brain Tumors

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02359565
First received: February 9, 2015
Last updated: July 14, 2017
Last verified: June 2017
February 9, 2015
July 14, 2017
May 22, 2015
April 1, 2018   (Final data collection date for primary outcome measure)
  • Change in the percentage of CD8+ T cells that are PD-1+ due to treatment with pembrolizumab (Stratum C) [ Time Frame: Baseline to after 6 weeks of treatment ]
    A 1-sample t-distribution-based confidence interval (or its non-parametric counterparts, as needed) will be used to estimate the average change in the percentage of CD8+ T cells that are PD-1+ due to treatment with pembrolizumab.
  • Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Within 30 days of treatment ]
    All adverse events observed during the dose finding period as well as during later courses will be summarized by stratum and by dose (if applicable). Separate tables for adverse events attributable to pembrolizumab will also be provided for each of the three strata.
  • Sustained objective response (partial response [PR] + complete response [CR]) [ Time Frame: Within 12 courses (approximately 9 months) ]
    Stratum specific exact confidence interval estimates will be provided for the sustained objective response rates. In addition, if adequate number of responses is observed to make such analyses meaningful, stratum-specific confirmed sustained objective response rates observed during treatment will be estimated by cumulative incidence functions.
  • Incidence of adverse events graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Within 30 days of treatment ]
    All adverse events observed during the dose finding period as well as during later courses will be summarized by stratum and by dose (if applicable). Separate tables for adverse events attributable to pembrolizumab will also be provided for each of the two strata.
  • Sustained objective response (PR + CR) [ Time Frame: Within 12 courses (approximately 9 months) ]
    Stratum specific exact confidence interval estimates will be provided for the sustained objective response rates. In addition, if adequate number of responses is observed to make such analyses meaningful, stratum-specific confirmed sustained objective response rates observed during treatment will be estimated by cumulative incidence functions.
Complete list of historical versions of study NCT02359565 on ClinicalTrials.gov Archive Site
  • Biomarker expression levels [ Time Frame: Up to 18 courses (approximately 13.5 months) ]
    The biomarker data generated as part of this study will be summarized via descriptive statistics and plots. The association between response and potential biomarkers will be evaluated by Fisher's exact or Chi-square test for categorical outcomes and two sample t-tests (or appropriate non-parametric counterparts) for continuous outcomes. Log-ranks tests or Cox regression models will also be used to explore associations between biomarkers and PFS and OS. These analyses will be done in a stratum specific fashion.
  • Changes in quantitative imaging parameters [ Time Frame: Baseline to up to 34 courses (approximately 25.5 months) ]
    Observed values of the proposed quantitative imaging parameters as well as changes in these parameters across time will be described and summarized via descriptive statistics and plots. Mixed effects models will be used to explore differences in estimated slope parameters of the quantitative imaging. Pairwise changes in these imaging parameters across various time points will also be described. T-tests (or their non-parametric equivalent) will be used to compare differences in pairwise changes between patients with progression vs. pseudoprogression/tumor inflammation.
  • Event-free survival [ Time Frame: Up to 3 years ]
    Kaplan-Meier estimates of event free survival distribution for all evaluable patients within each stratum will be provided.
  • Overall survival (OS) [ Time Frame: Date of diagnosis to the earliest date of death from any cause or to the date of last contact for patients who remain at risk for failure, assessed bi-annually up to 3 years and then yearly thereafter ]
    Kaplan-Meier estimates of OS distribution for all evaluable patients within each stratum will be provided. Log-ranks tests or Cox regression models will be used to explore associations between biomarkers and progression free survival (PFS) and OS.
  • Progression-free survival (PFS) [ Time Frame: Date of initial treatment to the earliest date of disease progression or death from any cause for patients who fail and to the date of last contact for patients who remain at risk for failure, assessed bi-annually up to 3 years and then yearly thereafter ]
    Log-ranks tests or Cox regression models will be used to explore associations between biomarkers and PFS and OS.
  • Radiologic response (Stratum C) [ Time Frame: Up to 3 years ]
    Will report any objective radiological responses observed in subjects who were not part of the primary cohort of progressive/recurrent high-grade gliomas (HGGs).
  • Event-free survival [ Time Frame: Up to 3 years ]
    Kaplan-Meier estimates of event free survival distribution for all evaluable patients within each stratum will be provided.
  • Overall survival (OS) [ Time Frame: Date of diagnosis to the earliest date of death from any cause or to the date of last contact for patients who remain at risk for failure, assessed up to 3 years ]
    Kaplan-Meier estimates of OS distribution for all evaluable patients within each stratum will be provided. Log-ranks tests or Cox regression models will be used to explore associations between biomarkers and PFS and OS.
  • Progression-free survival [ Time Frame: Date of initial treatment to the earliest date of disease progression or death from any cause for patients who fail and to the date of last contact for patients who remain at risk for failure, assessed up to 3 years ]
    Log-ranks tests or Cox regression models will be used to explore associations between biomarkers and PFS and OS.
  • Biomarker expression levels [ Time Frame: Up to 18 courses (approximately 13.5 months) ]
    The biomarker data generated as part of this study will be summarized via descriptive statistics and plots. The association between response and potential biomarkers will be evaluated by Fisher's exact or Chi-square test for categorical outcomes and two sample t-tests (or appropriate non-parametric counterparts) for continuous outcomes. Log-ranks tests or Cox regression models will also be used to explore associations between biomarkers and PFS and OS. These analyses will be done in a stratum specific fashion.
  • Pharmacokinetic (PK) parameters (volume of the central compartment, elimination rate constant, half-life, clearance, and area under the plasma concentration time curve) of pembrolizumab [ Time Frame: Day 1: pre-dose, end of infusion, 3, 6, 24, 48, 96, 168, 336 hours after infusion (course 1); pre-dose, end of infusion, 3, 6, 24, and 168 after infusion (course 3); pre-dose, end of infusion, 6, 24, 96, 168, and 336 after infusion (course 5) ]
    Plasma drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form. Pharmacokinetic parameters of interest will be estimated using population PK analysis. Dose proportionality in pharmacokinetic parameters will be investigated by performing one-way analysis of variance on dose-normalized parameters. The population parameters using nonlinear mixed effects modeling methods will also be estimated. Once the population parameters and corresponding covariance matrix are estimated, individual estimates can be obtained using post hoc analysis.
  • Changes in quantitative imaging parameters [ Time Frame: Baseline to up to 34 courses (approximately 25.5 months) ]
    Observed values of the proposed quantitative imaging parameters as well as changes in these parameters across time will be described and summarized via descriptive statistics and plots. Mixed effects models will be used to explore differences in estimated slope parameters of the quantitative imaging. Pairwise changes in these imaging parameters across various time points will also be described. T-tests (or their non-parametric equivalent) will be used to compare differences in pairwise changes between patients with true vs. pseudoprogression.
Not Provided
Not Provided
 
Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, or Hypermutated Brain Tumors
A Safety and Preliminary Efficacy Trial of MK-3475 (Pembrolizumab; Anti-PD-1) in Children With Recurrent, Progressive or Refractory High-Grade Gliomas (HGG) and DIPGs and Hypermutated Brain Tumors
This phase I trial studies the side effects and best dose of pembrolizumab and to see how well it works in treating younger patients with high-grade gliomas (brain tumors that are generally expected to be fast growing and aggressive), diffuse intrinsic pontine gliomas (brain stem tumors), or brain tumors with a high number of genetic mutations that have come back, progressed, or have not responded to previous treatment. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells.

PRIMARY OBJECTIVES:

I. To establish the safety and describe adverse effects associated with administration of the adult recommended dose of pembrolizumab (MK-3475) in children with recurrent, progressive or refractory non-brainstem high grade glioma (NB-HGG) and diffuse intrinsic pontine glioma (DIPG).

II. To estimate the sustained objective response rate, (complete response [CR] + partial response [PR], sustained for at least 9 weeks) associated with pembrolizumab (MK-3475) treatment for pediatric patients with recurrent, progressive or refractory NB-HGG or DIPG.

III. To establish the safety and describe adverse effects associated with administration of the adult recommended dose of pembrolizumab (MK-3475) in pediatric patients with progressive or recurrent hypermutated tumors, including those with conditional mismatch-repair deficiency (CMMRD) syndrome.

IV. To estimate the sustained response rate of pediatric patients with progressive or recurrent hypermutated NB-HGG, including those with CMMRD syndrome, treated with pembrolizumab (MK-3475).

V. To determine changes in the immunophenotypic profile of PD-1hi CD8+ T cells from serial peripheral blood samples obtained before and during treatment with pembrolizumab (MK-3475) in pediatric patients with hypermutated brain tumors, including those with CMMRD syndrome.

SECONDARY OBJECTIVES:

I. To assess the relationship between outcome (response and progression-free survival [PFS]) and potential biomarkers, including PD-L1 expression, patient immunophenotype, ribonucleic acid (RNA) signature profile, and tumor gene expression profile.

II. To estimate the duration of objective response, progression-free/event-free survival and document overall survival for patients with NB-HGG and DIPG treated with pembrolizumab (MK-3475).

III. To evaluate PD-L1 expression on archival tissue obtained from patients with non-brainstem high-grade glioma.

IV. To examine the ability of quantitative magnetic resonance (MR) spectroscopy and diffusion/weighted imaging/apparent diffusion coefficient (ADC) mapping to provide early assessment of tumor behavior and specifically distinguish pseudoprogression/tumor inflammation from tumor progression.

V. To explore the use of serial MR permeability (dynamic contrast-enhanced [DCE]) and MR perfusion (dynamic susceptibility contrast [DSC]) to determine if elevated relative cerebral blood volume (rCBV) and transfer coefficient (ktrans) can distinguish pseudoprogression/tumor inflammation from tumor progression in tumors treated on this protocol.

VI. To characterize biomarkers, patient immunophenotyping, mutational load (as determined by whole exome sequencing) and the tumor gene expression profile in patients with HGG receiving pembrolizumab (MK-3475).

VII. To estimate the duration of objective response, PFS/event free survival and document overall survival of pediatric patients with progressive or recurrent hypermutated NB-HGG, including those with CMMRD syndrome, treated with pembrolizumab (MK-3475).

VIII. To estimate the PFS and sustained objective response rate of pediatric patients with hypermutated progressive low grade gliomas including those with CMMRD, treated with pembrolizumab (MK-3475).

IX. To categorize the T-cell receptor repertoire in PD-1+ cells obtained from peripheral blood or from tumor tissue, when available, before and after treatment with pembrolizumab (MK-3475) in pediatric patients treated in stratum C (hypermutated brain tumors).

X. To define the specificity of T-cell receptors against tumor antigens identified in objective IX.

XI. To characterize functional features of T-cell populations after pembrolizumab (MK-3475) treatment and relate these findings to epigenetic programs within these cells.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 34 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 6 months for 3 years, and annually thereafter.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
  • Constitutional Mismatch Repair Deficiency Syndrome
  • Lynch Syndrome
  • Malignant Glioma
  • Recurrent Brain Neoplasm
  • Recurrent Diffuse Intrinsic Pontine Glioma
  • Refractory Brain Neoplasm
  • Refractory Diffuse Intrinsic Pontine Glioma
  • Procedure: Diffusion Tensor Imaging
    Correlative studies
    Other Names:
    • DIFFUSION TENSOR MRI
    • DT-MRI
    • DTI
  • Procedure: Diffusion Weighted Imaging
    Correlative studies
    Other Names:
    • Diffusion Weighted MRI
    • Diffusion-Weighted Magnetic Resonance Imaging
    • Diffusion-Weighted MR Imaging
    • Diffusion-Weighted MRI
    • DW-MRI
    • DWI
    • DWI MRI
    • DWI-MRI
    • MR Diffusion-Weighted Imaging
  • Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
    Correlative studies
    Other Names:
    • DCE MRI
    • DCE-MRI
    • DYNAMIC CONTRAST ENHANCED MRI
  • Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
    Correlative studies
    Other Names:
    • DSC-MRI
    • Dynamic Susceptibility Contrast-Enhanced MRI
    • DYNAMIC SUSCEPTIBILITY-CONTRAST MRI
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Procedure: Magnetic Resonance Spectroscopic Imaging
    Correlative studies
    Other Names:
    • 1H- Nuclear Magnetic Resonance Spectroscopic Imaging
    • 1H-nuclear magnetic resonance spectroscopic imaging
    • Magnetic Resonance Spectroscopy
    • MRS
    • MRS Imaging
    • MRSI
    • proton magnetic resonance spectroscopic imaging
  • Biological: Pembrolizumab
    Given IV
    Other Names:
    • Keytruda
    • Lambrolizumab
    • MK-3475
    • SCH 900475
  • Procedure: Perfusion Magnetic Resonance Imaging
    Correlative studies
    Other Name: magnetic resonance perfusion imaging
Experimental: Treatment (pembrolizumab)
Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 34 courses in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Procedure: Diffusion Tensor Imaging
  • Procedure: Diffusion Weighted Imaging
  • Procedure: Dynamic Contrast-Enhanced Magnetic Resonance Imaging
  • Procedure: Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging
  • Other: Laboratory Biomarker Analysis
  • Procedure: Magnetic Resonance Spectroscopic Imaging
  • Biological: Pembrolizumab
  • Procedure: Perfusion Magnetic Resonance Imaging
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
75
April 1, 2018
April 1, 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Tumor:

    • A diffuse intrinsic pontine glioma (DIPG) that is recurrent, progressive or refractory; histologic diagnosis is not required for patients with typical imaging findings of DIPG (defined as patients with a diffuse expansile mass centered in and involving at least 2/3 of the pons); patients with brainstem tumors who have undergone biopsy with a diagnosis of high-grade glioma or diffuse infiltrating glioma are also eligible
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Patients with DIPG who have tissue available are requested to submit similar tissue as patients with NB-HGG; however, this is not required for eligibility
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): All subjects must have measurable disease in 2-dimensions on MRI scan of the brain; disease should be consistently measured with the two largest perpendicular dimensions
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Patients must have received prior radiation therapy and/or chemotherapy and recovered from the acute treatment related toxicities (defined as =< grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study; there is no upper limit to the number of prior therapies that is allowed
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks prior to study enrollment or at least six (6) weeks if prior nitrosourea
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Biologic or investigational agent (anti-neoplastic): patient must have received their last dose of the investigational or biologic agent >= 7 days prior to study enrollment

    • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration must be discussed with and approved by the study chair
    • Monoclonal antibody treatment and/or agents with prolonged half-lives: at least three half-lives must have elapsed prior to enrollment
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses, etc.) at least 42 days prior to enrollment
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Patients must have had their last fraction of:

    • Craniospinal irradiation >= 3 months prior to enrollment
    • Other substantial bone marrow irradiation >= 6 weeks prior to enrollment
    • Local palliative radiation therapy (XRT) (small port) >= 2 weeks
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Patient must be >= 12 weeks since autologous bone marrow/stem cell transplant prior to enrollment
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Patients must be fully recovered from all acute effects of prior surgical intervention
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): All races and ethnic groups are eligible for this study
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Patients with neurological deficits should have deficits that are completely stable for a minimum of 1 week (7 days) prior to enrollment
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Karnofsky performance scale (KPS for > 16 years of age) or Lansky performance score (LPS for =< 16 years of age) assessed within two weeks of enrollment must be >= 70; patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Absolute neutrophil count >= 1.0 x 10^9 cells/L
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Platelets >= 100,000/mm^3 (unsupported, defined as no platelet transfusion within 7 days)
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Hemoglobin >= 8 g/dl (may receive transfusions)
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Albumin >= 2 g/dl
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Serum creatinine based on age/gender as noted below; patients that do not meet the criteria below but have a 24 hour creatinine clearance or glomerular filtration rate (GFR) (radioisotope or iothalamate) >= 70 ml/min/1.73 m^2 are eligible

    • 1 to < 2 years: 0.6 mg/dl
    • 2 to < 6 years: 0.8 mg/dl
    • 6 to < 10 years: 1 mg/dl
    • 10 to < 13 years: 1.2 mg/dl
    • 13 to < 16 years: 1.5 mg/dl (male), 1.4 mg/dl (female)
    • >= 16 years: 1.7 mg/dl (male), 1.4 mg/dl (female)
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Pulse oximetry > 93% on room air and no evidence of dyspnea at rest
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Patients must be off all colony-forming growth factor(s) for at least 1 week prior to registration (i.e. filgrastim, sargramostim, erythropoietin); 2 weeks must have elapsed for long-acting formulations
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Patients must be willing to use brief courses (at least 72 hours) of steroids as directed for potential inflammatory side effects of the therapy if recommended by their treating physician
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Female subjects of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test 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; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is to be treated with MK-3475 (pembrolizumab)
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): Patients of childbearing or child fathering potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity while being treated on this study and for 4 months after the last dose of study medication
  • INCLUSION CRITERIA FOR DIPG (STRATUM A - CURRENTLY CLOSED TO ACCRUAL): The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document, inclusive of assent where appropriate, according to institutional guidelines
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Tumor:

    • Patients must have a histologically confirmed diagnosis of a non-brainstem high-grade glioma that is recurrent, progressive or refractory; spinal primary disease is eligible
  • NCLUSION CRITERIA FOR NB-NGG (STRATUM B): Patients with non-brainstem high grade glioma must have adequate pre-trial FFPE tumor material available for use in the biology studies and genome wide sequencing; while tissue is required for PD-1, PD-L1 and immunophenotyping, patients will be deemed eligible for the study with a minimum of 10 unstained slides for the PD-1/PD-L1 immunohistochemical analysis
  • NCLUSION CRITERIA FOR NB-NGG (STRATUM B): All subjects must have measurable disease in 2-dimensions on MRI scan of the brain; disease should be consistently measured with the two largest perpendicular dimensions
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Patients must have received prior radiation therapy and/or chemotherapy and recovered from the acute treatment related toxicities (defined as =< grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy or radiotherapy prior to entering this study; there is no upper limit to the number of prior therapies that is allowed
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Patients must have received their last dose of known myelosuppressive anticancer therapy at least three (3) weeks prior to study enrollment or at least six (6) weeks if prior nitrosourea
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Biologic or investigational agent (anti-neoplastic): patient must have received their last dose of the investigational or biologic agent >= 7 days prior to study enrollment

    • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration must be discussed with and approved by the study chair
    • Monoclonal antibody treatment and/or agents with prolonged half-lives: at least three half-lives must have elapsed prior to enrollment
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses, etc.) at least 42 days prior to enrollment
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Patients must have had their last fraction of:

    • Craniospinal irradiation >= 3 months prior to enrollment
    • Other substantial bone marrow irradiation >= 6 weeks prior to enrollment
    • Local palliative XRT (small port) >= 2 weeks
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Patient must be >= 12 weeks since autologous bone marrow/stem cell transplant prior to enrollment
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Patients must be fully recovered from all acute effects of prior surgical intervention
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): All races and ethnic groups are eligible for this study
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Patients with neurological deficits should have deficits that are completely stable for a minimum of 1 week (7 days) prior to enrollment
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Karnofsky performance scale (KPS for > 16 years of age) or Lansky performance score (LPS for =< 16 years of age) assessed within two weeks of enrollment must be >= 70; patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Absolute neutrophil count >= 1.0 x 10^9 cells/L
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Platelets >= 100,000/mm^3 (unsupported, defined as no platelet transfusion within 7 days)
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Hemoglobin >= 8 g/dl (may receive transfusions)
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): ALT (SGPT) =< 3 x institutional upper limit of normal
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Albumin >= 2 g/dl
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Serum creatinine based on age/gender as noted below; patients that do not meet the criteria below but have a 24 hour creatinine clearance or GFR (radioisotope or iothalamate) >= 70 ml/min/1.73 m^2 are eligible

    • 1 to < 2 years: 0.6 mg/dl
    • 2 to < 6 years: 0.8 mg/dl
    • 6 to < 10 years: 1 mg/dl
    • 10 to < 13 years: 1.2 mg/dl
    • 13 to < 16 years: 1.5 mg/dl (male), 1.4 mg/dl (female)
    • >= 16 years: 1.7 mg/dl (male), 1.4 mg/dl (female)
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Pulse oximetry > 93% on room air and no evidence of dyspnea at rest
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Patients must be off all colony-forming growth factor(s) for at least 1 week prior to registration (i.e. filgrastim; sargramostim; erythropoietin); 2 weeks must have elapsed for long-acting formulations
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Patients must be willing to use brief courses (at least 72 hours) of steroids as directed for potential inflammatory side effects of the therapy if recommended by their treating physician
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Female subjects of childbearing potential must not be pregnant or breast-feeding; female patients of childbearing potential must have a negative serum or urine pregnancy test 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; pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is to be treated with MK-3475 (pembrolizumab)
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): Patients of childbearing or child fathering potential must be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity while being treated on this study and for 4 months after the last dose of study medication
  • INCLUSION CRITERIA FOR NB-NGG (STRATUM B): The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document, inclusive of assent where appropriate, according to institutional guidelines
  • INCLUSION CRITERIA FOR HYPERMUTATED BRAIN TUMORS (STRATUM C): Patients with brain tumors and increased tumor mutation burden as determined by

    • Confirmed diagnosis of CMMRD syndrome by CLIA-certified germline gene sequencing OR
    • Confirmation of high mutation burden by whole genome/exome sequencing performed in a CLIA-certified laboratory and/or the use of Foundation One next generation sequence panel or another CLIA approved targeted sequencing lab with publicly available correlations between number of mutations found in the panel and mutations per megabase and/or genome; for protocol purposes a high mutation burden will be defined as at least 100 non-synonymous coding-region mutations by whole exome/genome sequencing (well above two standard deviations of the number of median similar mutations described in pediatric central nervous system [CNS] cancers) AND/OR a high tumor mutation burden (TMB) or intermediate TMB based on the reporting parameters of the panel; TMB parameters provided for the Foundation One reports are high tumor mutation burden is >= 20 mutations per megabase or intermediate TMB is between 6 to 19 mutations per megabase
    • Confirmed diagnosis of Lynch syndrome by CLIA-certified germline gene sequencing; patients with Lynch syndrome will not be accounted for in primary objective unless their tumors are determined to have the minimum number of mutations described above but they will still
Sexes Eligible for Study: All
1 Year to 29 Years   (Child, Adult)
No
United States
 
 
NCT02359565
NCI-2015-00130
NCI-2015-00130 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
PBTC-045
PBTC-045 ( Other Identifier: Pediatric Brain Tumor Consortium )
PBTC-045 ( Other Identifier: CTEP )
UM1CA081457 ( U.S. NIH Grant/Contract )
No
Not Provided
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Eugene Hwang Pediatric Brain Tumor Consortium
National Cancer Institute (NCI)
June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP