Clinical Trials /

PVSRIPO in Recurrent Malignant Glioma

NCT02986178

Description:

This is a phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma.

Related Conditions:
  • Diffuse Midline Glioma, H3 K27M-Mutant
  • Glioblastoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PVSRIPO in Recurrent Malignant Glioma
  • Official Title: A Multicenter Phase 2 Study of Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) in Recurrent WHO Grade IV Malignant Glioma Patients

Clinical Trial IDs

  • ORG STUDY ID: Pro00077024
  • NCT ID: NCT02986178

Conditions

  • Malignant Glioma

Interventions

DrugSynonymsArms
PVSRIPOPolio/Rhinovirus Recombinant (PVSRIPO)

Purpose

This is a phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma.

Detailed Description

      This is a Phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients
      with recurrent World Health Organization (WHO) grade IV malignant glioma. The objective of
      this study is to investigate the safety and efficacy (anti-tumor response and survival) of
      PVSRIPO in recurrent WHO grade IV malignant glioma.

      Patients will be administered PVSRIPO intratumorally via convection-enhanced delivery (CED)
      using an intracerebral catheter placed within the enhancing portion of the tumor. Retreatment
      with PVSRIPO is allowed, provided retreatment eligibility criteria are met.

      All patients who receive PVSRIPO treatment will be included in efficacy and safety analyses.
    

Trial Arms

NameTypeDescriptionInterventions
Polio/Rhinovirus Recombinant (PVSRIPO)ExperimentalPolio/Rhinovirus Recombinant (PVSRIPO)
  • PVSRIPO

Eligibility Criteria

        INCLUSION CRITERIA SUMMARY:

          1. Patients must have a recurrent (first or second recurrence only, including this
             recurrence; transformation from a lower grade tumor to a WHO grade IV malignant glioma
             will be considered a first recurrence) supratentorial WHO grade IV malignant glioma
             based on imaging studies with measurable disease (a minimum measurement of 1 cm and
             maximum of 5.5 cm of contrast-enhancing tumor) with prior histopathology consistent
             with a WHO grade IV malignant glioma confirmed by the site's neuropathologist or the
             neuropathologist's designate.

          2. Male patients who are sexually active are eligible if he and/or his partner(s) meets
             the criteria outlined in the protocol. Female subjects are eligible if he and/or his
             partner(s) meets the criteria outlined in the protocol.

          3. Age ≥ 18 years of age.

          4. Karnofsky Performance Status (KPS) Score ≥ 70%.

          5. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy.

          6. Total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic
             pyruvic transaminase (SGPT), alkaline phosphatase ≤ 2.5 x normal prior to biopsy.

          7. Neutrophil count ≥ 1000 prior to biopsy.

          8. Hemoglobin ≥ 9 prior to biopsy.

          9. Platelet count ≥ 100,000/μL unsupported is necessary for eligibility on study;
             however, because of risks of intracranial hemorrhage with catheter placement, platelet
             count ≥ 125,000/μL is required for the patient to undergo biopsy and catheter
             insertion, which can be attained with the help of platelet transfusion.

         10. Creatinine ≤ 1.2 x normal range prior to biopsy.

         11. Positive serum anti-PV titer prior to biopsy.

         12. The patient must have received a boost immunization with trivalent inactivated IPOL™
             (Sanofi-Pasteur) at least 1 week, but less than 6 weeks, prior to administration of
             the study agent.

         13. At the time of biopsy, prior to administration of virus, the presence of recurrent
             tumor must be confirmed by histopathological analysis.

         14. A signed IRB-approve informed consent form (ICF).

         15. Able to undergo brain MRI with and without contrast.

        EXCLUSION CRITERIA SUMMARY:

          1. Females who are pregnant or breast-feeding.

          2. Patients with an impending, life-threatening cerebral herniation syndrome, based on
             the assessment of the study neurosurgeons, their designate, and the reviewer
             designated by the sponsor.

          3. Patients with severe, active co-morbidity, defined as in the protocol.

          4. Patients with a previous history of neurological complications due to PV infection.

          5. Patients who have not recovered from the toxic effects of prior chemo- and/or
             radiation therapy. Guidelines for this recovery period are dependent upon the specific
             therapeutic agent being used.

          6. Patients may not have received tumor treating fields (≤ 1 week), chemotherapy or
             bevacizumab ≤ 4 weeks [except for nitrosourea and lomustine (≤ 6 weeks); metronomic
             dosed chemotherapy, such as daily temozolomide, etoposide or cyclophosphamide (≤ 1
             week)] prior to starting the study drug.

          7. Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study
             drug unless patients have recovered from side effects of such therapy.

          8. Patients may not be less than 12 weeks from radiation therapy of the brain, unless
             progressive disease outside of the radiation field or 2 progressive scans at least 4
             weeks apart or histopathologic confirmation.

          9. Prior to enrollment, has not completed all standard of care treatments, including
             surgical procedure and radiation therapy (at least 59Gy) as outlined in the protocol.

         10. Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord;
             radiological evidence of multiple areas of active (growing) disease (active multifocal
             disease); tumors with contrast-enhancing tumor component crossing the midline
             (crossing the corpus callosum); extensive subependymal disease (tumor touching
             subependymal space is allowed); or extensive leptomeningeal disease (tumor touching
             leptomeninges is allowed).

         11. Patients with undetectable anti-tetanus toxoid immunoglobulin G (IgG).

         12. Patients with known history of agammaglobulinemia.

         13. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to
             admission for PVSRIPO infusion.

         14. Patients with worsening steroid myopathy (history of gradual progression of bilateral
             proximal muscle weakness, and atrophy of proximal muscle groups).

         15. Patients with prior, unrelated malignancy requiring current active treatment with the
             exception of cervical carcinoma in situ and adequately treated basal cell or squamous
             cell carcinoma of the skin.

         16. For patients randomized prior to V7, a known history of hypersensitivity to lomustine,
             dacarbazine, or any components of lomustine.

         17. Patients with active autoimmune disease requiring systemic immunomodulatory treatment
             within the past 3 months.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Radiographic Response Rate
Time Frame:24 months after initial PVSRIPO infusion and through study completion.
Safety Issue:
Description:Assess objective anti-tumor response based on iRANO criteria.

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:24 and 36 months after initial PVSRIPO infusion and through study completion.
Safety Issue:
Description:Overall Survival, relative to external control group(s)
Measure:Landmark Survival
Time Frame:24 and 36 months post-infusion and through study completion.
Safety Issue:
Description:Overall survival at 24 and 36 months and greater
Measure:Disease Control Rate Following PVSRIPO Infusion
Time Frame:24 and 36 months after initial PVSRIPO infusion and through study completion.
Safety Issue:
Description:The percentage of patients classified as non-progressive by radiographic response based on standard criteria.
Measure:Safety of PVSRIPO: proportion of patients who experience grade 3, 4, or 5 AEs
Time Frame:While on study; average of 12 to 36 months after initial PVSRIPO infusion.
Safety Issue:
Description:Within each cohort for those randomized prior to protocol version 7, as well as for those patients retreated with PVSRIPO, the proportion of patients who experience grade 3, 4, or 5 AEs that are possibly, probably, and definitely related to protocol treatment will be estimated.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Istari Oncology, Inc.

Trial Keywords

  • Glioblastoma
  • Glioma
  • PVSRIPO
  • Duke
  • Pro00077024
  • Brain tumor
  • Istari
  • Recurrent
  • GBM
  • rGBM

Last Updated

June 22, 2021