VXM01 Phase I Pilot Study in Patients With Operable Recurrence of a Glioblastoma

October 17, 2018 updated by: Vaximm GmbH

VXM01 Phase I Pilot Study in Patients With Operable Recurrence of a Glioblastoma to Examine Safety, Tolerability, Immune and Biomarker Response to the Investigational VEGFR-2 DNA Vaccine VXM01

VXM01 phase I pilot study in patients with operable recurrence of a glioblastoma to examine safety, tolerability, immune and biomarker response to the investigational VEGFR-2 DNA vaccine VXM01

Study Overview

Status

Status

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

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.

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

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

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 1

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

  • Germany
      • Heidelberg, Germany, 69120
        • Neurology Clinic and National Center for Tumor Diseases

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:

  1. Written informed consent, signed and dated
  2. Histologically diagnosed intracranial supratentorial malignant glioma (contrast-enhancing anaplastic astrocytoma WHO Grade III or glioblastoma WHO Grade IV).
  3. Male or female patients who must be post-menopausal for at least 2 years or surgically sterile.
  4. Age ≥18 years
  5. Evidence of tumor progression following at least one therapy regimen that must have contained radiation and chemotherapy with temozolamid, as measured by MRI
  6. Candidates for a tumor reoperation
  7. Neurosurgical intervention should be postponable for 30 days
  8. Laboratory results (clinical chemistry, hematology, urine, liver enzymes, creatinine) without clinically relevant abnormalities
  9. Patients must be able to undergo MRI
  10. No concomitant medication with dexamethasone at the time of vaccination
  11. No active infection at the time of vaccination
  12. Karnofsky performance status >70
  13. Appropriate hematologic parameters (for immunomonitoring): leukocytes ≥4.0 x 109 / L, lymphocytes ≥0.6 x 109 / L
  14. Tumor samples available for pathology review, central detection of T-cell responses in the peripheral blood and in the tumor tissue
  15. No medical or social conditions that may interfere with study outcome and follow-up

Exclusion Criteria:

  1. Treatment in any other clinical trial within 30 days before screening
  2. Known positive test results for Hepatitis B surface antigen , hepatitis C virus antibodies, human immunodeficiency virus antibodies -1/-2
  3. Any other condition or treatment that, in the opinion of the investigator, might interfere with the study or current drug or substance abuse
  4. Inability to understand the protocol requirements, instructions and study-related restrictions, the nature, scope, and possible consequences of the study
  5. Unlikely to comply with the protocol requirements, instructions and study-related restrictions; e.g., uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study
  6. Pregnancy or breast feeding
  7. Positive for anti-typhoid IgG/IgM antibodies according to the onsite test on Day 0

  8. Cardiovascular disease defined as:

    Uncontrolled hypertension (systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg)

    Arterial thromboembolic event within 6 months before randomization including:

    • Myocardial infarction
    • Unstable angina pectoris
    • Cerebrovascular accident
    • Transient ischemic attack
  9. Congestive heart failure New York Heart Association grade III to IV
  10. Serious ventricular arrhythmia requiring medication
  11. Clinically significant peripheral artery disease > grade 2b according to Fontaine
  12. Intracranial ischemic stroke within 6 months before randomization
  13. History of intracranial hemorrhage
  14. Hemoptysis within 6 months before randomization
  15. Esophageal varices
  16. Upper or lower gastrointestinal bleeding within 6 months before inclusion (Day 0)
  17. Significant traumatic injury or surgery within 4 weeks before randomization
  18. Non-healing wound, incomplete wound healing, bone fracture or any history of gastrointestinal ulcers within three years before inclusion, or positive gastroscopy within 3 months before inclusion
  19. Gastrointestinal fistula
  20. Thrombolysis therapy within 4 weeks before randomization
  21. Presence of any acute or chronic systemic infection
  22. Major surgical procedures, or open biopsy within 4 weeks before randomization

  23. Chronic concurrent therapy within 2 weeks before and during the treatment period up to Day 35 with:

    • Corticosteroids (except steroids for adrenal failure or emesis prophylaxis up to 4 mg daily dose) or immunosuppressive agents
    • Antibiotics
    • Bevacizumab
    • Any cancer anti-angiogenic treatment
  24. Chemotherapy from screening until reoperation (Day 35)
  25. Known multi-drug resistant gram-negative germ
  26. History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the study results or render the patient at high risk for treatment complications
  27. Women of childbearing potential
  28. Any condition which results in an undue risk for the patient during the study participation according to the investigator

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: N/A
  • Interventional Model: Single Group 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: VXM01
VXM01 10E6 or 10E7 CFU
Drug: VXM01
Oral immunotherapy targeting VEGFR2

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
Safety and tolerability taking into account treatment-limiting toxicities (TLTs)
Time Frame: 12 months
AEs listed together with information on onset, duration, severity, seriousness, relationship to the study drug, relationship to chemotherapy and to the underlying disease, outcome, and action taken. Frequency tables by System Organ Class and preferred term.
12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Immune Response by Enzyme Linked Immuno Spot (ELISpot)
Time Frame: 12 months
Patient-individual VEGFR-2 specific T cell responses will be determined by ELISpot using cryopreserved peripheral blood mononuclear cells
12 months
Serum biomarker Response by Enzyme Linked Immuno Sorbent Assay (ELISA)
Time Frame: 12 months
Biomarkers including VEGF A and Collagen IV determined from periphaeral blood samples
12 months
Vascular normalization index (VNI) including tumor perfusion acc. to Sorensen 2009
Time Frame: 12 months
Determined by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) (ktrans), dynamic susceptibility contrast imaging (DSC), blood volume maps (cerebral blood volume [CBV] of smaller vessels) and collagen IV
12 months
Tumor immune cell infiltration by tumor tissue immunohistochemistry
Time Frame: 35 days
Tumor tissue immunohistochemistry staining including Evaluations of effector T cell infiltration, regulatory T-cells (Treg), myeloid derived suppressor cells (MDSC)
35 days
Tumor response or progression on MRI acc. to Response Assessment in Neuro-Oncology (RANO) criteria
Time Frame: 12 months
MRI comprising the National Brain Tumor Society /EORTC protocol for gliomas
12 months
Clinical Response including time to progression, progression free survival, overall survival
Time Frame: 12 months
12 months
Biodistribution and shedding of VXM01 bacteria
Time Frame: 10 days
Bacterial vector tissue biodistribution, persistence, and shedding of viable Ty21a bacteria (VXM01) determined by cultivation of stool samples
10 days

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.
Vaximm GmbH

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: Wolfgang Wick, MD, Neurology Clinic and National Center for Tumor Diseases

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

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.
May 1, 2016

Primary Completion (Actual)

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.
August 1, 2017

Study Completion (Actual)

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.
July 1, 2018

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).
March 16, 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.
March 18, 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.
March 24, 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.
October 19, 2018

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.
October 17, 2018

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.
October 1, 2018

More Information

Terms related to this study

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.
  • VXM01-02-DE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

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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