Inclusion Criteria:
1. Disease Status. Patients must have a recurrent supratentorial WHO Grade IV malignant
glioma based on imaging studies with measurable disease (≥ 1 cm or ≤ 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,
Roger McLendon, or his designate.
2. Age. Due to the potential implications of the treatment on the developing CNS, all
patients must be ≥ 18 years of age at the time of entry into the study.
3. Performance Status. The patient must have a Karnofsky Performance Score (KPS) of ≥
70% at the time of entry.
4. Laboratory Studies.
- - Platelet count ≥ 125,000/microliter prior to biopsy.
Platelets ≥
100,000/microliter prior to infusion.
- - Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy.
- - Positive serum anti-poliovirus titer prior to biopsy (except for retreatment)
- Creatinine ≤ 1.2 x normal prior to biopsy.
- - Total bilirubin, SGOT, SGPT, alkaline phosphatase ≤ 2.5 x normal prior to
biopsy.
- - Neutrophil count ≥ 1000 prior to biopsy.
- - Hemoglobin ≥ 9 prior to biopsy.
5. Poliovirus Immunization Booster. The subject must have received a boost immunization
with trivalent inactivated IPOL™ (Sanofi-Pasteur) at least 1 week prior to
administration of the study agent.
6. Disease Confirmation. At the time of biopsy, prior to administration of virus, the
presence of recurrent tumor must be confirmed by histopathological analysis.
7. Informed Consent. A signed informed consent form approved by the Duke University
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.
8. Brain MRI. Able to undergo brain MRI with and without contrast.
Exclusion Criteria:
1. Pregnancy. Because of the unknown risk of virus administration potentially affecting
a developing fetus or growing infant, females who are pregnant or breast-feeding
during the study period will be excluded. Adults of reproductive potential not
employing an effective method of birth control will be excluded. 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.
2. Disease Status. Because patients will receive drug intracerebrally, patients with an
impending, life-threatening cerebral herniation syndrome, based on the assessment of
the study neurosurgeons, Allan Friedman, John Sampson, or Peter Fecci, or their
designate, will be excluded.
3. Medical Conditions. Because the potential toxicities from the agent being studied in
this protocol may be similar to some known diseases or may be more dangerous in the
context of certain known diseases, the following patients will be excluded to avoid
confounding the study results:
- - 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.
- - Unstable or severe intercurrent medical conditions such as severe heart (New
York Heart Association Class 3 or 4) or known lung (FEV1 < 50%) disease,
uncontrolled diabetes mellitus.
Albumin is added to the agent as a stabilizer. Patients with a
known allergy will be excluded.
- - Current or history of anaphylactic reaction to gadolinium.
Gadolinium is used
as contrast for the MRI.
4. Previous Poliomyelitis. A history of neurological complications due to poliovirus
infection would imply previous virus replication in the CNS. Based on animal
studies, previous exposure to poliovirus administered intracerebrally can reduce
subsequent virus replication in the CNS.
5. Prior Therapy. Patients who have not recovered from the toxic effects of prior
chemotherapy and/or radiation therapy will be excluded. 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 d disease outside of the radiation field or 2 progressive scans at
least 4 weeks apart or histopathologic confirmation.
- - Patients must have completed all standard of care treatments including surgical
procedure and radiation therapy (at least 59Gy):
- 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 status is unknown at the time of screening, patients must have
received at least one chemotherapy regimen prior to participating in this
trial.
6. Location and Extent of Tumor. Because of the potential toxicities from the agent,
patients with neoplastic lesions in the brainstem, cerebellum or spinal cord,
radiological evidence of multifocal disease, or leptomeningeal disease. Patients
with evidence of diffuse subependymal disease or tumor in the brainstem, cerebellum,
spinal cord, or CSF will be excluded. Since the study agent is a local treatment,
patients with radiological evidence of active (growing) multifocal disease, tumors
extending into or crossing the corpus callosum or leptomeningeal disease, will be
excluded.
7. Subjects must not have diagnosis of agammaglobulinemia. Patients with the following
will be excluded:
- - Undetectable anti-tetanus toxoid IgG (except for retreatment)
- Known history of agammaglobulinemia.
8. Patient on greater than 4mg per day of dexamethasone within the 2 weeks prior to
admission for PVSRIPO infusion. 9. Patient has worsening steroid myopathy (history of gradual progression of bilateral
proximal muscle weakness, and atrophy of proximal muscle groups)
10. 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.Eligibility Criteria for Retreatment:
Subjects can be considered for PVSRIPO retreatment if they meet some of the pertinent
inclusion and exclusion criteria above. In addition, the subject must also satisfy the
following criteria:
- - Patient must have benefited from initial treatment with PVSRIPO (i.e. be at least 12
months following their initial PVSRIPO infusion).
- - Patient must have a recurrence of their supratentorial WHO grade IV malignant glioma
based on imaging studies with measurable disease (≥ 1 cm of contrast-enhancing
tumor).
- - At the time of biopsy, prior to administration of virus, the presence of recurrent
tumor must be confirmed by histopathological analysis, unless already proven within
the last 3 months via tissue sampling (biopsy or resection).
- - The patient must have received a new boost immunization with trivalent inactivated
IPOL™ (Sanofi-Pasteur) at least 1 week and no more than 4 weeks prior to
re-administration of the study agent.
The boost immunization may be obtained
locally, prior to signing consent, as long as the patient has been informed about
this study procedure via phone script.
- - A new signed informed consent form for retreatment approved by the Duke University
Institutional Review Board (IRB) will be required for retreatment.
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.
