Clinical Trials /

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

NCT02359565

Description:

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), brain tumors with a high number of genetic mutations, ependymoma or medulloblastoma that have come back (recurrent), progressed, or have not responded to previous treatment (refractory). Immunotherapy with monoclonal antibodies, such as pembrolizumab, may induce changes in the body's immune system, and may interfere with the ability of tumor cells to grow and spread.

Related Conditions:
  • Diffuse Intrinsic Pontine Glioma
  • Ependymoma
  • Glioma
  • Malignant Brain Neoplasm
  • Medulloblastoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma
  • Official Title: A Safety and Preliminary Efficacy Trial of MK-3475 (Pembrolizumab; Anti-PD-1) in Children With Recurrent, Progressive or Refractory Diffuse Intrinsic Pontine Glioma (DIPG), Non-Brainstem High-Grade Gliomas (NB-HGG), Ependymoma, Medulloblastoma or Hypermutated Brain Tumors

Clinical Trial IDs

  • ORG STUDY ID: NCI-2015-00130
  • SECONDARY ID: NCI-2015-00130
  • SECONDARY ID: PBTC-045
  • SECONDARY ID: PBTC-045
  • SECONDARY ID: PBTC-045
  • SECONDARY ID: UM1CA081457
  • NCT ID: NCT02359565

Conditions

  • Constitutional Mismatch Repair Deficiency Syndrome
  • Lynch Syndrome
  • Malignant Glioma
  • Progressive Ependymoma
  • Progressive Medulloblastoma
  • Recurrent Brain Neoplasm
  • Recurrent Childhood Ependymoma
  • Recurrent Diffuse Intrinsic Pontine Glioma
  • Recurrent Medulloblastoma
  • Refractory Brain Neoplasm
  • Refractory Diffuse Intrinsic Pontine Glioma
  • Refractory Ependymoma
  • Refractory Medulloblastoma

Interventions

DrugSynonymsArms
PembrolizumabKeytruda, Lambrolizumab, MK-3475, SCH 900475Treatment (pembrolizumab)

Purpose

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), brain tumors with a high number of genetic mutations, ependymoma or medulloblastoma 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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To establish the safety and describe adverse effects associated with administration of the
      adult recommended dose of pembrolizumab (MK-3475) in each stratum separately.

      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 diffuse intrinsic
      pontine glioma (DIPG), non-brainstem high grade glioma (NB-HGG), ependymoma or
      medulloblastoma.

      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 constitutional 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) and
      potential biomarkers, including PD-L1 expression, patient immunophenotype, ribonucleic acid
      (RNA) signature profile, mutational profile, tumor gene expression and circulating tumor
      deoxyribonucleic acid (DNA) (ctDNA).

      II. To estimate the duration of objective response in patients with measurable disease at
      baseline and estimate progression-free/event-free/overall survival for patients in each
      stratum treated with pembrolizumab (MK-3475).

      III. To evaluate PD-L1 expression on archival tissue obtained from pediatric patients with
      eligible primary central nervous system (CNS) tumors.

      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), the tumor gene expression profile and ctDNA in patients receiving
      pembrolizumab (MK-3475).

      VII. To estimate the duration of objective response, progression-free survival/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 progression-free survival (PFS) of all patients enrolled on stratum C
      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 at 30 days, every 3 months for
      1 year, then every 6 months for up to 3 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pembrolizumab)ExperimentalPatients 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.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  INCLUSION CRITERIA FOR STRATA A, B, D AND E

          -  Tumor: patient must have one of the following diagnoses to be eligible:

          -  Stratum A, currently closed to enrollment: Patients must have a recurrent, progressive
             or refractory DIPG following radiation therapy with or without chemotherapy

               -  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

          -  Stratum B: Patients must have a histologically confirmed diagnosis of a non-brainstem
             high-grade glioma (NB-HGG) that is recurrent, progressive or refractory following
             therapy which included radiotherapy; spinal primary disease is eligible

          -  Stratum D: Patients must have a histologically confirmed diagnosis of ependymoma that
             is recurrent, progressive or refractory following therapy which included radiotherapy

          -  Stratum E: Patients must have a histologically confirmed diagnosis of medulloblastoma
             that is recurrent, progressive or refractory following therapy which included
             radiotherapy

          -  Patients must have adequate pre-trial formalin-fixed paraffin-embedded (FFPE) tumor
             material available for use in the biology studies mutational analysis and genome wide
             sequencing for each stratum

               -  Patients with DIPG who have tissue available are requested to submit similar
                  tissue as patients in other strata; however, this is not required for eligibility

          -  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

          -  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

          -  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

          -  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

          -  Patient must have completed immunotherapy (e.g. tumor vaccines, oncolytic viruses,
             etc.) at least 42 days prior to enrollment

          -  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

          -  Patient must be >= 12 weeks since autologous bone marrow/stem cell transplant prior to
             enrollment

          -  Patients must be fully recovered from all acute effects of prior surgical intervention

          -  All races and ethnic groups are eligible for this study

          -  Patients with neurological deficits should have deficits that are completely stable
             for a minimum of 1 week (7 days) prior to enrollment

          -  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

          -  Absolute neutrophil count >= 1000 cells/uL

          -  Platelets >= 75,000 cells /uL (unsupported, defined as no platelet transfusion within
             7 days)

          -  Hemoglobin >= 8 g/dl (may receive transfusions)

          -  Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)

          -  Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x
             institutional upper limit of normal

          -  Albumin >= 2 g/dl

          -  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)

          -  Pulse oximetry > 93% on room air and no evidence of dyspnea at rest

          -  Patients must be off all colony-forming growth factor(s) for at least 1 week prior to
             registration (e.g. filgrastim, sargramostim, erythropoietin); 2 weeks must have
             elapsed for long-acting formulations

          -  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

          -  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)

          -  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 6 months after the last dose of study medication

          -  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 STRATUM C: Diagnosis of hypermutated brain tumors Patients with
             brain tumors and increased tumor mutation burden as determined by

               -  Confirmed diagnosis of CMMRD syndrome by Clinical Laboratory Improvement Act
                  (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 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 be eligible for this study

               -  Low-grade tumors in patients with CMMRD or Lynch syndrome do not have to reach
                  the threshold of 100 mutations for study inclusion

          -  INCLUSION CRITERIA FOR STRATUM C: Patients must have a histologically confirmed
             primary brain tumor that is recurrent, progressive or refractory; inclusion criteria
             encompasses all types of brain tumors (e.g. gliomas, embryonal tumors or any other
             type of brain tumor as long as other eligibility criteria are met;

               -  Patients with high-grade gliomas are eligible for this clinical trial at least 2
                  weeks after completion of radiotherapy independent of tumor
                  progression/recurrence as long as they are not enrolled on any other therapeutic
                  clinical trial and there is macroscopic residual disease

               -  Patients with other concomitant tumors associated with CMMRD syndrome including
                  gastrointestinal polyps/adenomas and carcinomas, lymphomas and leukemias will be
                  eligible as long as they are not requiring anticancer therapy directed against
                  these other cancers and meet all other eligibility criteria

          -  INCLUSION CRITERIA FOR STRATUM C: Patients must have adequate pre-trial FFPE tumor
             material available and be willing to provide a blood sample for use in the genome wide
             sequencing studies; while tissue is required for genome-wide sequencing of tumor and
             germline samples, patients will be deemed eligible for the study with a minimum of
             approximately 10 unstained slides for the planned analysis

          -  INCLUSION CRITERIA FOR STRATUM C: All subjects must have measurable disease in
             2-dimensions on MRI scan of the brain and/or spine; disease should be consistently
             measured with the two largest perpendicular dimensions

          -  INCLUSION CRITERIA FOR STRATUM C: Patients must have received prior radiotherapy
             and/or chemotherapy with the following exceptions:

               -  Patients with secondary CNS cancers after a previous medical problem/malignancy
                  who cannot receive full dose of radiotherapy (> 50 Gy) as long as they meet all
                  other eligibility criteria

               -  Patients with progressive low-grade gliomas and CMMRD or Lynch syndrome Patients
                  must have 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 STRATUM C: 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 STRATUM C: 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 STRATUM C: Patient must have completed immunotherapy (e.g.
             tumor vaccines, oncolytic viruses, etc.) at least 42 days prior to enrollment

          -  INCLUSION CRITERIA FOR STRATUM C: 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 STRATUM C: Patient must be:

               -  >= 12 weeks since autologous bone marrow/stem cell transplant prior to enrollment

               -  >= 5 years since allogeneic bone marrow transplant prior to enrollment with no
                  evidence of active graft versus (vs.) host disease

          -  INCLUSION CRITERIA FOR STRATUM C: Patients must be fully recovered from all acute
             effects of prior surgical intervention

          -  INCLUSION CRITERIA FOR STRATUM C: All races and ethnic groups are eligible for this
             study

          -  INCLUSION CRITERIA FOR STRATUM C: 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 STRATUM C: 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 >= 60; 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 STRATUM C: Absolute neutrophil count >= 1000 cells/uL

          -  INCLUSION CRITERIA FOR STRATUM C: Platelets >= 75,000 cells/uL (unsupported, defined
             as no platelet transfusion within 7 days)

          -  INCLUSION CRITERIA FOR STRATUM C: Hemoglobin >= 8 g/dl (may receive transfusions)

          -  INCLUSION CRITERIA FOR STRATUM C: Total bilirubin =< 1.5 times institutional upper
             limit of normal (ULN)

          -  INCLUSION CRITERIA FOR STRATUM C: ALT (SGPT) =< 3 x institutional upper limit of
             normal

          -  INCLUSION CRITERIA FOR STRATUM C: Albumin >= 2 g/dl

          -  INCLUSION CRITERIA FOR STRATUM C: 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 STRATUM C: Pulse oximetry > 93% on room air and no evidence of
             dyspnea at rest

          -  INCLUSION CRITERIA FOR STRATUM C: 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 STRATUM C: 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 STRATUM C: 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 STRATUM C: 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 6
             months after the last dose of study medication

          -  INCLUSION C
      
Maximum Eligible Age:29 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0
Time Frame:Within 30 days of treatment
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:Log-ranks tests or Cox regression models will be used to explore associations between biomarkers and PFS and OS.
Measure:Event-free survival
Time Frame:Up to 3 years
Safety Issue:
Description:Kaplan-Meier estimates of event free survival distribution for all evaluable patients within each stratum will be provided.
Measure: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
Safety Issue:
Description: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.
Measure:Radiologic response (Stratum C)
Time Frame:Up to 3 years
Safety Issue:
Description:Will report any objective radiological responses observed in subjects who were not part of the primary cohort of progressive/recurrent high-grade gliomas (HGGs).
Measure:Biomarker expression levels
Time Frame:Up to 18 courses (approximately 13.5 months)
Safety Issue:
Description: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.
Measure:Changes in quantitative imaging parameters
Time Frame:Baseline to up to 34 courses (approximately 25.5 months)
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

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