A Toll-like Receptor Agonist as an Adjuvant to Tumor Associated Antigens (TAA) Mixed With Montanide ISA-51 VG With Bevacizumab for Patients With Recurrent Glioblastoma

January 8, 2020 updated by: NYU Langone Health
This is a phase II study to determine the immunogenicity and efficacy of a vaccine composed of tumor associated long synthetic peptides mixed with Montanide ISA-51 VG administered with polyinosinic-polycytidylic acid - poly-L-lysine carboxymethylcellulose (Poly-ICLC) and bevacizumab in adults with recurrent glioblastoma.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

All patients will receive the same dose of vaccine, Poly-ICLC and bevacizumab. The therapy consists of 3 blocks. During the first block, patients will receive bevacizumab every 2 weeks for 2 doses. During block 2, patients will receive vaccine + Poly-ICLC + bevacizumab on weeks 1, 3, 5 and 7. An MRI will be performed after week 7 therapy. If there is no significant progression, then the patients will continue with block 3. During block 3, therapy consists of vaccine + Poly-ICLC monthly and bevacizumab every 2 weeks for 10 months. Keyhole limpet hemocyanin (KLH) will be given as a positive control with the first vaccine. Immune studies will be performed in all patients enrolled in this study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10016
        • NYU Perlmutter Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Disease Status. Patients with first recurrence of glioblastoma (WHO IV). Patients must have histological confirmation of glioblastoma (WHO grade IV) either at diagnosis or at first recurrence. Patients with diffuse intrinsic pontine glioma (DIPG) are not eligible.
  • Karnofsky performance status > 50. Patients who are unable to walk because of paralysis but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
  • Adequate organ function:

Hematologic: absolute lymphocyte count > 200/mm3 Platelets > 100,000 Hepatic:AST/ALT < 5 x the upper limit of institutional normal Total bilirubin < 1.5 x the upper limit of institutional normal Renal: serum creatinine < 1.5 mg/ml; Urine protein/creatinine ratio < 2.0 at screening Cardiac: Hypertension must be well controlled on stable doses of medication. BP must be < 140/90.

  • Life expectancy >3 months
  • Patients must have fully recovered from previous surgery, chemotherapy, radiotherapy and biologic therapy. No surgery, chemotherapy, radiation therapy or immunotherapy within 4 weeks prior to the first dose of study agent or bevacizumab (6 weeks for nitrosureas).
  • Patients must have no measurable disease or minimal residual disease defined as <1.5cm2 enhancement. Patients may have surgery to achieve < 1.5cm2 residual.
  • Tumor tissue must be available either from initial diagnosis or relapse for testing of antigen expression.
  • Informed consent must be signed by the patient. Individuals who lack capacity to sign consent will be excluded. Patients must be able to read and/or understand the details of the study and provide written evidence of informed consent as approved by the IRB.

Exclusion Criteria:

  • Serious illness, such as uncontrolled infections requiring antibiotics
  • History of immunodeficiency disease (such as HIV) or autoimmune disease except vitiligo
  • Concomitant treatment with systemic dexamethasone (or it's equivalent) greater than 2mg/day. Topical (but not at the proposed vaccination site) or inhalational steroids are permitted
  • Participation in any other clinical trial involving another investigational agent within 4 weeks prior the first dose of study agent.
  • Pregnant or lactating women are not permitted.
  • Women of child-bearing potential not using medically acceptable means of contraception.
  • Prior vaccine therapy for high grade glioma is not allowed.
  • Other malignancy within 3 years prior to entry into the study, except for treated early-stage melanoma or non-melanoma skin cancer, or cervical carcinoma in situ
  • Significant bleeding history
  • Patients with serious or non-healing wound, ulcer, or bone fractures are not eligible.
  • Patients must not have a history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months prior to study entry.
  • Patients must not have a known bleeding diathesis or coagulopathy.
  • Patients must not have had significant vascular disease (eg, aortic aneurysm requiring surgical repair, deep venous or arterial thrombosis) within the last 6 months prior to study entry.
  • Patients must not have evidence of new CNS hemorrhage on baseline MRI obtained within 14 days prior to study enrollment.
  • Patients must not have a known thrombophilic condition (i.e. protein S, protein C or antithrombin III deficiency, Factor V Leiden, Factor II G20210A mutation, homocysteinemia or antiphospholipid antibody syndrome). Testing is not required in patients without thrombophilic history.
  • Patients must not have a history of stroke, myocardial infarction, transient ischemic attack (TIA), severe or unstable angina, peripheral vascular disease, or grade II or greater congestive heart failure within the past 6 months prior to study entry.
  • Patients must not have serious and inadequately controlled cardiac arrhythmias.
  • Patients must not have a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of bevacizumab or anticipation of need for major surgical procedure during the course of the study.
  • Patients must not have minor surgical procedures, fine needle aspirations, or core biopsies within 7 days prior to study enrollment.
  • Patients with organ allografts.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Block 1
Drug: Bevacizumab
Bevacizumab is a humanized monoclonal antibody that targets vascular endothelial growth factor (VEGF), a proangiogenic factor which aids in tumor vessel formation.
Other Names:
  • Hiltonol®
Experimental: Block 2
Drug: Bevacizumab
Bevacizumab is a humanized monoclonal antibody that targets vascular endothelial growth factor (VEGF), a proangiogenic factor which aids in tumor vessel formation.
Other Names:
  • Hiltonol®
Biological: Peptide Vaccine

Vaccine of long synthetic peptides encoding T cell epitopes in tumor associated antigens.

Vaccine Consists of:

EGFRvIII peptide 100 mcg IL13Ralpha peptide 100 mcg EphA2 peptide 100 mcg Her2/neu peptide 100 mcg YKL-40 peptide 100 mcg

Drug: Poly-ICLC as immune adjuvant
Poly-ICLC is a toll like receptor 3 agonist which directly activates dendritic cells and triggers natural killer cells to kill tumor cells.
Drug: Keyhole limpet hemocyanin (KLH)
Potent Immunogen used in vaccine approaches for a number of diseases including cancer, AIDS, and infectious diseases
Experimental: Block 3
Drug: Bevacizumab
Bevacizumab is a humanized monoclonal antibody that targets vascular endothelial growth factor (VEGF), a proangiogenic factor which aids in tumor vessel formation.
Other Names:
  • Hiltonol®
Biological: Peptide Vaccine

Vaccine of long synthetic peptides encoding T cell epitopes in tumor associated antigens.

Vaccine Consists of:

EGFRvIII peptide 100 mcg IL13Ralpha peptide 100 mcg EphA2 peptide 100 mcg Her2/neu peptide 100 mcg YKL-40 peptide 100 mcg

Drug: Poly-ICLC as immune adjuvant
Poly-ICLC is a toll like receptor 3 agonist which directly activates dendritic cells and triggers natural killer cells to kill tumor cells.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Assays to determine immunity to the vaccine's antigen
Time Frame: 9 Weeks
9 Weeks
Measure of Humoral Immune Responses measured by ELISA
Time Frame: 9 Weeks
9 Weeks
Antigen specific CD4+ and CD8+ T-cell reactivity to the peptide antigens measured by intracellular cytokine staining
Time Frame: 9 Weeks
Measured either ex-vivo (assayed directly from thawed PBMCs) or following in-vitro pre-sensitization.
9 Weeks
CD4+ and CD8+ T cell reactivity to KLH measured by T cell proliferation quantified by tritiated thymidine incorporation
Time Frame: 9 Weeks
9 Weeks
Measure of Tumor Responses measured by the Response Evaluation Criteria in Solid Tumors (RECIST).
Time Frame: 1 Day
1 Day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NYU Langone Health

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
MOUNT SINAI HOSPITAL

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sharon Gardner, MD, New York University Medical School

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2016

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2019

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 13, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 28, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 13, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 8, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 15-00044

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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