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

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ClinicalTrials.gov Identifier: NCT02718443
Recruitment Status : Completed
First Posted : March 24, 2016
Last Update Posted : October 19, 2018
Sponsor:
Information provided by (Responsible Party):
Vaximm GmbH

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Glioblastoma Drug: VXM01 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 Start Date : May 2016
Actual Primary Completion Date : August 2017
Actual Study Completion Date : July 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: VXM01
VXM01 10E6 or 10E7 CFU
Drug: VXM01
Oral immunotherapy targeting VEGFR2




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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)

  5. 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

  6. Clinical Response including time to progression, progression free survival, overall survival [ Time Frame: 12 months ]
  7. 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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): NCT02718443


Locations
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Germany
Neurology Clinic and National Center for Tumor Diseases
Heidelberg, Germany, 69120
Sponsors and Collaborators
Vaximm GmbH
Investigators
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Principal Investigator: Wolfgang Wick, MD Neurology Clinic and National Center for Tumor Diseases

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Responsible Party: Vaximm GmbH
ClinicalTrials.gov Identifier: NCT02718443     History of Changes
Other Study ID Numbers: VXM01-02-DE
First Posted: March 24, 2016    Key Record Dates
Last Update Posted: October 19, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Additional relevant MeSH terms:
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Glioblastoma
Recurrence
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Disease Attributes
Pathologic Processes