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Malignant GliomaPhase 1/2NCT03973879

Combination of PVSRIPO and Atezolizumab for Adults With Recurrent Malignant Glioma

A Phase 1/2 study testing PVSRIPO and Atezolizumab in people with Malignant Glioma, run by Darell Bigner.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Glioma
What is being tested?
PVSRIPO and Atezolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Feb 2020to Jan 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
  • 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
  • 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%
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  • 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

Who cannot join

  • 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:
  • Patients with an active infection requiring intravenous 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 unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
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  • Patients with known lung (forced expiratory volume in the first second of expiration (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 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)
  • 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
  • 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.

About this study

Official title: A Phase 1b/2 Trial of PVSRIPO in Combination With Atezolizumab in Recurrent WHO Grade IV Malignant Glioma

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.

Read the 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.

Being tested
PVSRIPO, Atezolizumab
Keywords
PVSRIPO, Atezolizumab, Glioblastoma, Glioma, Bigner, Randazzo, Brain tumor, Duke, Istari, Pro00100677, Genentech
Medical subject headings
Glioma, Glioblastoma, Brain Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PVSRIPOBiological

    Oncolytic polio/rhinovirus recombinant

  • AtezolizumabDrug

    Also called Tecentriq

    Antibody

Study groups in NCT03973879
Study groupRoleWhat they receive
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.
Receives: Biological: PVSRIPO; Drug: Atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of unacceptable adverse events

    Any Grade 3 or any Grade 4 toxicity that is not reversible within 2 weeks, or any life-threatening event, or treatment-related death.

    Measured: 14 days after first atezolizumab treatment

  2. Proportion of patients alive

    Proportion of patients alive at 24 months after PVSRIPO infusion

    Measured: 24 months after PVSRIPO infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2019
  2. Study startFeb 2020 (estimated)
  3. Primary completionJan 2024 (estimated)
  4. Study completionJan 2024 (estimated)

Why it stopped: Re-submission Planned

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03973879
Sponsor's protocol ID
Pro00100677
Status last verified
Feb 2020
First submitted
31 May 2019
Last updated
11 Feb 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing PVSRIPO and Atezolizumab in people with Malignant Glioma, run by Darell Bigner.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 11 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of unacceptable adverse events (time frame: 14 days after first atezolizumab treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03973879.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2020.

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