Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma
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|ClinicalTrials.gov Identifier: NCT02359565|
Recruitment Status : Recruiting
First Posted : February 10, 2015
Last Update Posted : July 3, 2018
|Condition or disease||Intervention/treatment||Phase|
|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||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||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||110 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||May 22, 2015|
|Estimated Primary Completion Date :||April 1, 2020|
|Estimated Study Completion Date :||April 1, 2020|
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.
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
Procedure: Perfusion Magnetic Resonance Imaging
Other Name: magnetic resonance perfusion imaging
- 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 ]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.
- 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.
- 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.
- 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.
- 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).
- 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.
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): NCT02359565
|United States, California|
|Children's Hospital Los Angeles||Suspended|
|Los Angeles, California, United States, 90027|
|Lucile Packard Children's Hospital Stanford University||Suspended|
|Palo Alto, California, United States, 94304|
|United States, Colorado|
|Children's Hospital Colorado||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Site Public Contact 888-823-5923 email@example.com|
|Principal Investigator: Kathleen M. Dorris|
|United States, District of Columbia|
|Children's National Medical Center||Suspended|
|Washington, District of Columbia, United States, 20010|
|United States, Georgia|
|Children's Healthcare of Atlanta - Egleston||Suspended|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|Lurie Children's Hospital-Chicago||Suspended|
|Chicago, Illinois, United States, 60611|
|United States, New York|
|Memorial Sloan Kettering Cancer Center||Suspended|
|New York, New York, United States, 10065|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center||Suspended|
|Cincinnati, Ohio, United States, 45229|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh of UPMC||Suspended|
|Pittsburgh, Pennsylvania, United States, 15224|
|United States, Tennessee|
|St. Jude Children's Research Hospital||Recruiting|
|Memphis, Tennessee, United States, 38105|
|Contact: Site Public Contact 888-823-5923 firstname.lastname@example.org|
|Principal Investigator: Zsila S. Sadighi|
|United States, Texas|
|Texas Children's Hospital||Suspended|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Eugene Hwang||Pediatric Brain Tumor Consortium|