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.
