New DCVax Clinical Trial with Opdivo is on clinicaltrials.gov siliconinvestor.com Cell-Autologous Lung Tumor Vaccine and Nivolumab in Treating Patients With Recurrent Glioblastoma
https://clinicaltrials.gov/ct2/show/NCT03014804?term=dcvax&rank=7
This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2016 by Jonsson Comprehensive Cancer Center
Sponsor:
Jonsson Comprehensive Cancer Center
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT03014804
First received: November 30, 2016
Last updated: January 5, 2017
Last verified: November 2016
History of Changes
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 Purpose
This phase II trial studies the side effects of dendritic cell-autologous lung tumor vaccine and nivolumab and to see how well they work in treating patients with glioblastoma that has come back. Vaccines made from a person's tumor cells may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving dendritic cell-autologous lung tumor vaccine and nivolumab may work better in treating patients with glioblastoma.
Condition Intervention Phase Giant Cell Glioblastoma
Gliosarcoma
Oligodendroglioma
Recurrent Glioblastoma
Small Cell Glioblastoma
| Biological: Dendritic Cell-Autologous Lung Tumor Vaccine
Other: Laboratory Biomarker Analysis
Biological: Nivolumab
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
| Phase 2
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| Study Type: | Interventional | | Study Design: | Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment | | Official Title: | A Phase II Clinical Trial Evaluating Combination Therapy Using DCVax-L (Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen) and Nivolumab (an Anti-PD-1 Antibody) for Subjects With Recurrent Glioblastoma Multiforme |
Resource links provided by NLM:
Genetics Home Reference related topics: lung cancer
MedlinePlus related topics: Cancer Lung Cancer
Drug Information available for: Nivolumab
Genetic and Rare Diseases Information Center resources: Glioblastoma Gliosarcoma Oligodendroglioma Glioma Neuroepithelioma
U.S. FDA Resources
Further study details as provided by Jonsson Comprehensive Cancer Center:
Primary Outcome Measures:Incidence of adverse events assessed by National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.03 [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]
Will be compared between groups and to those reported for historical standards, including subjects treated with nivolumab in prior trials.
Overall Survival (OS) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
The overall survival curves will be displayed using a Kaplan-Meier curve for the pooled and individual treatments. A one-sample log-rank test will also be completed as a sensitivity analysis for the same survival rate assumption as the primary efficacy analysis, and a two-sample log-rank test will be used to compare the survival distribution between the two arms.
Secondary Outcome Measures:Overall Survival rate [ Time Frame: 9 months ] [ Designated as safety issue: No ]
The overall survival curves will also be displayed using a Kaplan-Meier curve for the pooled and individual treatments. Estimated proportions of surviving subjects at 9 months will be provided along with the two-sided 95% CIs.
Overall Survival rate [ Time Frame: 12 months ] [ Designated as safety issue: No ]
The overall survival curves will also be displayed using a Kaplan-Meier curve for the pooled and individual treatments. Estimated proportions of surviving subjects at 12 months will be provided along with the two-sided 95% CIs.
Overall Survival rate [ Time Frame: 18 months ] [ Designated as safety issue: No ]
The overall survival curves will also be displayed using a Kaplan-Meier curve for the pooled and individual treatments. Estimated proportions of surviving subjects at 18 months will be provided along with the two-sided 95% CIs.
Progression Free Survival (PFS) [ Time Frame: From treatment initiation to first progression or death assessed up to 12 months. ] [ Designated as safety issue: No ]
Kaplan Meier estimates will be provided along with the one-sided 95% lower bound on the survival rate. PFS survival will be compared between groups using a log-rank test.
Quality of Life (QoL) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
Will be summarized descriptively for available subjects, and shifts from day 0 will be summarized for post-baseline assessments using the European Organization for Research and Treatment of Cancer (EORTC) Overall Quality of Life (QoL) questionnaire.
Number of participants with complete response (CR) [ Time Frame: Up to 12 months of follow up after initiation of treatment ] [ Designated as safety issue: No ]
Rates of CR will be provided at fixed intervals where tumor size is evaluated. Exact two-sided CIs for the response rate will be provided and the denominator will include subjects with available information or who have previously died or progressed. A Fisher's exact test will be used to compare the test that the number of CR, CR+PR, and CR+PR+SD subjects is homogeneous across the treatment arms.
Number of participants with partial response (PR) [ Time Frame: Up to 12 months of follow up after initiation of treatment ] [ Designated as safety issue: No ]
Rates of PR will be provided at fixed intervals where tumor size is evaluated. Exact two-sided CIs for the response rate will be provided and the denominator will include subjects with available information or who have previously died or progressed. A Fisher's exact test will be used to compare the test that the number of CR, CR+PR, and CR+PR+SD subjects is homogeneous across the treatment arms.
Number of participants with stable disease (SD) [ Time Frame: Up to 12 months of follow up after initiation of treatment ] [ Designated as safety issue: No ]
Rates of SD will be provided at fixed intervals where tumor size is evaluated. Exact two-sided CIs for the response rate will be provided and the denominator will include subjects with available information or who have previously died or progressed. A Fisher's exact test will be used to compare the test that the number of CR, CR+PR, and CR+PR+SD subjects is homogeneous across the treatment arms.
Number of participants with progressive disease (PD) [ Time Frame: Up to 12 months of follow up after initiation of treatment ] [ Designated as safety issue: No ]
Rates of PD will be provided at fixed intervals where tumor size is evaluated. Exact two-sided CIs for the response rate will be provided and the denominator will include subjects with available information or who have previously died or progressed. A Fisher's exact test will be used to compare the test that the number of CR, CR+PR, and CR+PR+SD subjects is homogeneous across the treatment arms.
Objective response rate (ORR) defined as the percentage of participants with CR + PR [ Time Frame: Up to 12 months of follow up after initiation of treatment ] [ Designated as safety issue: No ]
Rates of ORR will be provided at fixed intervals where tumor size is evaluated.
Response/Stable Disease Rate (RSDR) defined as the percentage of participants demonstrating CR+PR+SD [ Time Frame: Up to 12 months of follow up after initiation of treatment ] [ Designated as safety issue: No ]
Rates of RSDR will be provided at fixed intervals where tumor size is evaluated.
Other Outcome Measures:Changes in PET in lymph nodes [ Time Frame: Baseline up to 12 months ] [ Designated as safety issue: No ]
Correlated with TIL density or clonality, clinical outcome, T cell measures in peripheral blood and clinical toxicity. Descriptive statistics, confidence intervals, or inferential analyses will comprise a set of exploratory analyses.
Changes in PET in organ tissue [ Time Frame: Baseline up to 12 months ] [ Designated as safety issue: No ]
Correlated with tumor infiltrating lymphocytes (TIL) density or clonality. Descriptive statistics, confidence intervals, or inferential analyses will comprise a set of exploratory analyses.
Changes of PET in tumor [ Time Frame: Baseline up to 12 months ] [ Designated as safety issue: No ]
Correlated with TIL density or clonality, clinical outcome, T cell measures in peripheral blood and clinical toxicity. Descriptive statistics, confidence intervals, or inferential analyses will comprise a set of exploratory analyses.
Effect of nivolumab on peripheral blood lymphocyte and TIL proliferation (CD8+/Ki-67+ staining) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
Descriptive statistics, confidence intervals, or inferential analyses will comprise a set of exploratory analyses.
Difference in Progression Free Survival (PFS) of participants treated with combination treatment (Group 1) versus single treatment (group 2) [ Time Frame: Up to 12 months follow up after initiation of treatment ] [ Designated as safety issue: No ]
Difference in the rates of contrast-enhanced tumor change over time of participants treated with combination treatment (Group 1) versus single treatment (group 2) [ Time Frame: Up to 12 months follow up after initiation of treatment ] [ Designated as safety issue: No ]
Difference in Overall Survival (OS) of participants treated with combination treatment (Group 1) versus single treatment (group 2) [ Time Frame: Up to 12 months follow up after initiation of treatment ] [ Designated as safety issue: No ]
Difference in Landmark survival at 9 month of participants treated with combination treatment (Group 1) versus single treatment (group 2) [ Time Frame: Up to 9 months follow up after initiation of treatment ] [ Designated as safety issue: No ]
Difference in Landmark survival at 12 month of participants treated with combination treatment (Group 1) versus single treatment (group 2) [ Time Frame: Up to 12 months follow up after initiation of treatment ] [ Designated as safety issue: No ]
Difference in Landmark survival at 18 month of participants treated with combination treatment (Group 1) versus single treatment (group 2) [ Time Frame: Up to 18 months follow up after initiation of treatment ] [ Designated as safety issue: No ]
Number of somatic mutations in each pre-treatment tumor sample [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
Correlated with T lymphocytic response in tumor after DCVax-L +/- nivolumab. Descriptive statistics, confidence intervals, or inferential analyses will comprise a set of exploratory analyses.
Oligoclonal T cell populations within tumor tissue [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
The magnitude of morphological changes correlated with clinical responses. Descriptive statistics, confidence intervals, or inferential analyses will comprise a set of exploratory analyses.
Association of Progression Free Survival (PFS) and Overall Survival (OS) with MGMT methylation status [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
The difference of PFS and OS between participants with methylated MGMT promotor and participants with unmethylated MGMT promotor enrolled in each treatment group
Analysis of PD-L1 membrane protein expression level on monocytes in two groups [ Time Frame: from baseline, up to 12 months follow up ] [ Designated as safety issue: No ]
Difference in expression level on monocytes at baseline and over time (Week 8, the End of Treatment, month 6 and month 18) compared between two groups
PD-1 and PD-L1 immunohistochemical expression [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
Immunohistochemical staining (IHC) will be used to determine the difference in expression between archived tumor tissue samples and on study tumor tissue samples. Archived tumor tissue samples and on study tumor tissue samples are obtained in paraffin blocks or FFPE tissue slides, and are processed by IHC technique for antitumor expression of PD-1 and PD-L1. Multi-plex IHC stained will be performed to assess: 1) the proportion of PD-L1 expression on GFAP+ tumor cells versus myeloid cells (CD68+ or CD163+) within the tumor microenvironment; and 2) the proportion of PD-1 expression on CD4 or CD8 TIL; and 3) the proximity of CD4/8 TIL to PD-L1+ cells in the tumor microenvironment.
PD-1 and PD-L1 immunohistochemistry density [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
Immunohistochemistry will be used to measure the difference in PD-1 and PD-L1 expression between density with clinical responses to combination therapy examined. Descriptive statistics, confidence intervals, or inferential analyses will comprise a set of exploratory analyses.
PD-1 and PD-L1 immunohistochemistry clonality [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
Immunohistochemistry will be used to measure the difference in PD-1 and PD-L1 expression between clonality with clinical responses to combination therapy examined. Descriptive statistics, confidence intervals, or inferential analyses will comprise a set of exploratory analyses.
Evaluate the effects of the study treatment on CD4+/8+ T cell ratios in two groups [ Time Frame: From baseline up to 12 months of follow up ] [ Designated as safety issue: No ]
Fluorescence-activated cell sorting assay will be used to measure T CD4+/8+ T cell ratios
Evaluate the effects of the study treatment on T cell subset proliferation and populations in two groups [ Time Frame: From baseline up to 12 months of follow up ] [ Designated as safety issue: No ]
Fluorescence-activated cell sorting assay will be used to measure T cell subset proliferation and population
Evaluate the effects of the study treatment on negative costimulatory molecule expression in two groups [ Time Frame: From baseline up to 12 months of follow up ] [ Designated as safety issue: No ]
Fluorescence-activated cell sorting assay will be used to measure negative costimulatory molecule expression
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| Estimated Enrollment: | 30 | | Study Start Date: | April 2017 | | Estimated Primary Completion Date: | April 2019 (Final data collection date for primary outcome measure) |
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