Clinical Trials /

Combination of PVSRIPO and Atezolizumab for Adults With Recurrent Malignant Glioma

NCT03973879

Description:

This study evaluates the safety of PVSRIPO treatment in combination with Atezolizumab in patients with WHO grade IV malignant glioma. All patients will receive a single PVSRIPO infusion followed by atezolizumab infusions every three weeks for up to two years.

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

Withdrawn

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Combination of PVSRIPO and Atezolizumab for Adults With Recurrent Malignant Glioma
  • Official Title: A Phase 1b/2 Trial of PVSRIPO in Combination With Atezolizumab in Recurrent WHO Grade IV Malignant Glioma

Clinical Trial IDs

  • ORG STUDY ID: Pro00100677
  • NCT ID: NCT03973879

Conditions

  • Malignant Glioma

Interventions

DrugSynonymsArms
PVSRIPOPVSRIPO + Atezolizumab
AtezolizumabTecentriqPVSRIPO + Atezolizumab

Purpose

This study evaluates the safety of PVSRIPO treatment in combination with Atezolizumab in patients with WHO grade IV malignant glioma. All patients will receive a single PVSRIPO infusion followed by atezolizumab infusions every three weeks for up to two years.

Detailed Description

      The purpose of this phase1b/2 study of atezolizumab in combination with oncolytic
      polio/rhinovirus recombinant (PVSRIPO) in patients with recurrent World Health Organization
      (WHO) grade IV malignant glioma is to assess the safety of the combination of PVSRIPO +
      atezolizumab, as well as describe the survival of patients receiving this novel therapy
      combination. Patients will receive an intratumoral infusion of PVSRIPO followed by
      atezolizumab treatment with possible surgical resection after the first atezolizumab
      treatment at the discretion of the treating neurosurgeon.
    

Trial Arms

NameTypeDescriptionInterventions
PVSRIPO + AtezolizumabExperimentalSingle PVSRIPO infusion at a dose of 5x10^7 tissue culture infected dose (TCID50). Atezolizumab infusions at a dose of 1200 mg every three weeks for up to two years.
  • PVSRIPO
  • Atezolizumab

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 WHO grade IV malignant glioma confirmed
             by the study pathologist, Roger McLendon, or his designate. Assuming patient meets all
             other criteria, the treating neurosurgeon must confirm placement of infusion catheter
             tip can occur ≥ 1cm from ventricles and that procedures can be completed per their
             medical judgement and in keeping with the protocol, when considering individual lesion
             characteristics including location relative to eloquent brain function.

          -  Patient or partner(s) meets one of the following criteria:

               1. Non-childbearing potential (i.e. not sexually active, physiologically incapable
                  of becoming pregnant, including any female who is post-menopausal or surgically
                  sterile, or any male who has had a vasectomy). Surgically sterile females are
                  defined as those with a documented hysterectomy and/or bilateral oophorectomy or
                  tubal ligation. Postmenopausal for purposes of this study is defined as 1 year
                  without menses.; or

               2. Childbearing potential and agrees to use one of the following methods of birth
                  control: approved hormonal contraceptives (e.g. birth control pills, patches,
                  implants, or infusions), an intrauterine device, or a barrier method of
                  contraception (e.g. a condom or diaphragm) used with spermicide.

          -  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 ≥ 100,000/µl unsupported is necessary for eligibility on the study;
             however, because of risks of intracranial hemorrhage with catheter placement, platelet
             count ≥ 120,000/µl is required for the patient to undergo biopsy and catheter
             insertion, which can be attained with the help of platelet transfusion

          -  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, but less than 6 weeks, 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

          -  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:

               1. Patients with an active infection requiring intravenous treatment or having an
                  unexplained febrile illness (Tmax > 99.5°F/37.5°C)

               2. Patients with known immunosuppressive disease or known human immunodeficiency
                  virus infection

               3. Patients with unstable or severe intercurrent medical conditions such as severe
                  heart disease (New York Heart Association Class 3 or 4)

               4. Patients with known lung (forced expiratory volume in the first second of
                  expiration (FEV1) < 50%) disease or uncontrolled diabetes mellitus

               5. Patients with albumin allergy

               6. Patients with gadolinium allergy

          -  Patients with a previous history of neurological complications due to PV 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 of the brain, 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 for recurrent glioma,
             including surgical procedure and radiation therapy (at least 59 Gy)

               1. If the MGMT promoter in their tumor is known to be unmethylated, patients are not
                  mandated to have received chemotherapy prior to participating in this trial

               2. 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) 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).

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

          -  Patients with known history of agammaglobulinemia

          -  Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to the
             first atezolizumab 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 atezolizumab, or any components
             of atezolizumab

          -  Patients with active autoimmune disease requiring systemic immunomodulatory treatment
             within the past 3 months

        NOTE: If a patient is treated for an unrelated malignancy other than the exceptions noted
        within the past 3 years, a letter from their treating oncologist for the unrelated
        malignancy must be on file confirming that said unrelated malignancy does not require
        current active treatment (prophylactic like tamoxifen OK) and that the patient is stable
        with low risk of recurrence/death within 3 years from this other malignancy (i.e., disease
        is stable). If this letter is not on file, a consult with the Sponsor's medical designee is
        required prior to submitting the patient for consideration of enrollment in the trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of unacceptable adverse events
Time Frame:14 days after first atezolizumab treatment
Safety Issue:
Description:Any Grade 3 or any Grade 4 toxicity that is not reversible within 2 weeks, or any life-threatening event, or treatment-related death.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Darell D. Bigner, MD, PhD

Trial Keywords

  • PVSRIPO
  • Atezolizumab
  • Glioblastoma
  • Glioma
  • Bigner
  • Randazzo
  • Brain tumor
  • Duke
  • Istari
  • Pro00100677
  • Genentech

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