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:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PVSRIPO With/Without Lomustine
  • Official Title: A Randomized Phase 2 Study of Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) Alone or in Combination With Lomustine 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)
LomustineGleostinePolio/Rhinovirus Recombinant (PVSRIPO) + Lomustine

Purpose

This is a randomized phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) alone or in combination with the chemotherapy drug lomustine in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.

Detailed Description

      This is a randomized phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) alone
      or in combination with the chemotherapy drug lomustine in adult patients with recurrent
      World Health Organization (WHO) grade IV malignant glioma at the Preston Robert Tisch Brain
      Tumor Center (PRTBTC) at Duke. The primary objective of this study is to assess the survival
      of subjects receiving PVSRIPO with or without a single dose of lomustine relative to the
      survival observed in a historical control group. The secondary objective is to assess the
      safety of PVSRIPO in combination with lomustine. Subjects will be randomized to receive
      either PVSRIPO alone, or PVSRIPO in combination with a single dose of lomustine 8 weeks
      after PVSRIPO infusion, to evaluate the impact of these treatment regimens on 24-month
      survival. PVSRIPO will be delivered intratumorally by convection-enhanced delivery (CED)
      using an intracerebral catheter placed within the enhancing portion of the tumor. Subjects
      randomized to the lomustine arm will receive a single oral dose of 110 mg/m2 lomustine 8
      weeks after PVSRIPO administration. The target accrual for the study is 62 patients, 31
      patients per arm. All patients who are randomized and receive PVSRIPO treatment will be
      included in efficacy and safety analyses..
    

Trial Arms

NameTypeDescriptionInterventions
Polio/Rhinovirus Recombinant (PVSRIPO)ExperimentalPolio/Rhinovirus Recombinant (PVSRIPO)
    Polio/Rhinovirus Recombinant (PVSRIPO) + LomustineExperimentalPolio/Rhinovirus Recombinant (PVSRIPO) + Lomustine
    • Lomustine

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients must have a recurrent supratentorial WHO grade IV malignant glioma based on
                 imaging studies with measurable disease (≥ 1 cm and ≤ 5.5 cm of contrast-enhancing
                 tumor). Prior histopathology consistent with a World Health Organization (WHO) grade
                 IV malignant glioma confirmed by the study pathologist
    
              -  Age ≥ 18 years of age at the time of entry into the study.
    
              -  Karnofsky Performance Score (KPS) ≥ 70%
    
              -  Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy
    
              -  Total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic
                 pyruvic transaminase (SGPT), alkaline phosphatase ≤ 2.5 x normal prior to biopsy
    
              -  Neutrophil count ≥ 1000 prior to biopsy
    
              -  Hemoglobin ≥ 9 prior to biopsy
    
              -  Platelet count ≥ 125,000/µl prior to biopsy; Platelet count ≥ 100,000/µl prior to
                 infusion
    
              -  Creatinine ≤ 1.2 x normal range prior to biopsy
    
              -  Positive serum anti-poliovirus titer prior to biopsy
    
              -  The patient must have received a boost immunization with trivalent inactivated IPOL™
                 (Sanofi-Pasteur) at least 1 week prior to administration of the study agent.
    
              -  At the time of biopsy, prior to administration of virus, the presence of recurrent
                 tumor must be confirmed by histopathological analysis.
    
              -  A signed informed consent form approved by the Institutional Review Board (IRB) will
                 be required for patient enrollment into the study. Patients must be able to read and
                 understand the informed consent document and must sign the informed consent
                 indicating that they are aware of the investigational nature of this study.
    
              -  Able to undergo brain MRI with and without contrast
    
            Exclusion Criteria:
    
              -  Females who are pregnant or breast-feeding. Adults of reproductive potential not
                 employing an effective method of birth control. Sexually active women of child
                 bearing potential, whose partner is male, must use medically accepted birth control.
                 Sexually active men, whose partner is a female of child bearing potential, must use a
                 medically accepted birth control.
    
              -  Patients with an impending, life-threatening cerebral herniation syndrome, based on
                 the assessment of the study neurosurgeons or their designate
    
              -  Patients with severe, active co-morbidity, defined as follow:
    
                   -  Patients with an active infection requiring treatment or having an unexplained
                      febrile illness (Tmax > 99.5°F/37.5°C)
    
                   -  Patients with known immunosuppressive disease or known human immunodeficiency
                      virus infection
    
                   -  Patients with impaired cardiac function or clinically significant cardiac
                      disease, such as congestive heart failure requiring treatment (New York Heart
                      Association Class ≥ 2), uncontrolled hypertension or clinically significant
                      arrhythmia; QTcF > 470 msec on electrocardiogram (ECG) if performed or
                      congenital long QT syndrome; acute myocardial infarction or unstable angina
                      pectoris < 3 months prior to study
    
                   -  Patients with known lung (FEV1 < 50%) disease or uncontrolled diabetes mellitus
    
                   -  Patients with albumin allergy
    
                   -  Patients with gadolinium allergy
    
              -  Patients with a previous history of neurological complications due to poliovirus
                 infection
    
              -  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.
    
              -  Patients may not have received chemotherapy or bevacizumab ≤ 4 weeks [except for
                 nitrosourea (6 weeks) or metronomic dosed chemotherapy such as daily etoposide or
                 cyclophosphamide (1 week)] prior to starting the study drug unless patients have
                 recovered from side effects of such therapy
    
              -  Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study
                 drug unless patients have recovered from side effects of such therapy.
    
              -  Patients may not be less than 12 weeks from radiation therapy, unless progressive
                 disease outside of the radiation field or 2 progressive scans at least 4 weeks apart
                 or histopathologic confirmation
    
              -  Patients who have not completed all standard of care treatments, including surgical
                 procedure and radiation therapy (at least 59Gy)
    
                   -  If the MGMT (O(6)-methylguanine-DNA methyltransferase) promoter in their tumor
                      is known to be unmethylated, patients are not mandated to have received
                      chemotherapy prior to participating in this trial.
    
                   -  If the MGMT promoter in their tumor is known to be methylated or the MGMT
                      promoter methylation status is unknown at time of screening, patients must have
                      received at least one chemotherapy regimen prior to participating in this trial.
    
              -  Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord,
                 radiological evidence of active (growing) multifocal disease, subependymal or
                 leptomeningeal disease
    
              -  Patients with undetectable anti-tetanus toxoid IgG (Immunoglobulin G)
    
              -  Patients with known history of agammaglobulinemia
    
              -  Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to
                 admission for PVSRIPO infusion
    
              -  Patients with worsening steroid myopathy (history of gradual progression of bilateral
                 proximal muscle weakness, and atrophy of proximal muscle groups)
    
              -  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
    
              -  Patients with a known history of hypersensitivity to lomustine, dacarbazine, or any
                 components of lomustine
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:24-month overall survival
    Time Frame:24 months after administration of PVSRIPO
    Safety Issue:
    Description:The percentage of participants alive at 24 months after the administration of PVSRIPO. Overall survival is calculated from the date of administration of PVSRIPO until the date of death, or the date of last follow-up if alive. Kaplan-Meier methods are used to estimate overall survival.

    Secondary Outcome Measures

    Measure:Percentage of participants with grade 3, 4, or 5 treatment-related adverse events
    Time Frame:Up to 24 months; events will be assessed continuously from the time of catheter placement for PVSRIPO administration until 30 days after a participant goes off study.
    Safety Issue:
    Description:The percentage of particpants with grade 3, 4 or 5 adverse events possibly, probably or definitely related to administration of PVSRIPO or Lomustine.

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Darell D. Bigner, MD, PhD

    Trial Keywords

    • Glioblastoma
    • Glioma
    • PVSRIPO
    • Duke
    • Pro00077024
    • Peters
    • Brain tumor
    • Bigner

    Last Updated

    March 22, 2017