| Eligibility |
As a general principle, subjects eligible for access must:
- Have a serious or life-threatening condition;
- Have no appropriate, comparable, or satisfactory alternative treatment available, or
such alternatives have been tried without clinical success, including clinical
studies; and
- Be unable to participate in a PVSRIPO clinical trial that is currently open to
enrollment.
Subjects are eligible if all of the following criteria are met:
1. Age = 18 years at time of consent.
2. The subject is able and willing to provide written informed consent.
3. Subjects with:
1. Prior histologically confirmed supratentorial GBM based on imaging studies with
measurable disease (= 1 cm of contrast-enhancing tumor; multifocal acceptable if
total enhancing disease burden considered acceptable); OR
2. Subjects with GBM > 5.5 cm in diameter (these are excluded from current clinical
studies of PVSRIPO), but for whom PVSRIPO is judged by Investigator to be
appropriate for treatment. Such cases may include subjects with large resection
cavities with residual infusible tumor, where the cavity allows space for
expansion of peritumoral edema (PTE); OR
3. Subjects with recurrent GBM (rGBM) who benefitted from prior PVSRIPO treatment;
OR
4. Subjects with GBM who do not meet eligibility for a clinical trial of PVSRIPO
currently open to enrollment, but who would otherwise benefit from treatment. If
appropriate, comparable or satisfactory alternative treatments approved for GBM
must have been tried without clinical success, or in the opinion of the
Investigator the subject is not a good candidate for those treatments but is
anticipated to potentially benefit from PVSRIPO treatment without additional
risk.
4. Before catheter placement based on screening MRI and at the time of catheter placement
via CT prior to infusion, neurosurgical investigator should confirm placement of
infusion catheter within or through the progressive enhancing tumor is feasible and at
a safe distance relative to eloquent brain function, with the tip of the catheter
being placed within these guidelines:
1. Within the enhancing portion or in the vicinity of enhancement of target lesion
(ie, infiltrative disease)
2. = 0.5 cm from ventricles
3. = 1 cm deep into the brain
4. = 0.5 cm from the corpus callosum
Any changes from the above catheter tip placement guidelines require discussion and
prior approval from the Sponsor.
5. Women of childbearing potential must have a negative urine or serum (Beta-Human
Chorionic Gonadotropin, ß-hCG) pregnancy test prior to PVSRIPO infusion.
6. Women and men in the study, and female partners of men in the study, must use highly
effective birth control for 6 months after the last dose of PVSRIPO.
7. Karnofsky Performance Status (KPS) Score = 70%.
8. Undergone prior vaccination against PV and received a boost immunization with
trivalent IPOL® (Sanofi-Pasteur SA) at least 1 week, but less than 6 weeks, prior to
administration of PVSRIPO (within 6 months of PVSRIPO retreatment). Note: Patients who
are unsure of their prior vaccination status/who have not been vaccinated must provide
proof of vaccination and/or evidence of anti-PV immunity prior to enrollment, as
applicable.
9. Prior to biopsy (if required)/catheter placement, the following must be met: Platelet
count = 100,000/µL unsupported is necessary for eligibility; however, because of risks
of intracranial hemorrhage with catheter placement, platelet count = 125,000/µL is
required for the subject to undergo biopsy/catheter insertion, which can be attained
via platelet transfusion (ie, supported).
Subjects with any of the following are excluded:
1. Women who are pregnant or breast-feeding.
2. Have an impending, life-threatening cerebral herniation syndrome, based on the
assessment of the institution's neurosurgeons, and/or designee(s).
3. Have severe, active co-morbidity, defined as follows:
1. Have an active infection requiring intravenous treatment or having an unexplained
febrile illness (Tmax > 99.5°F/37.5°C).
2. Have known immunosuppressive disease or known human immunodeficiency virus
infection.
3. Have unstable or severe intercurrent medical conditions such as severe heart
disease (New York Heart Association Class 3 or 4).
4. Have known lung (forced expiratory volume in the first second of expiration
[FEV1] < 50%) disease or uncontrolled diabetes mellitus.
5. Have an albumin allergy or serious gadolinium allergy/anaphylaxis.
4. Local laboratory values within two weeks of biopsy/catheter placement that meet any of
the following:
1. Prothrombin (PT) and activated Partial Thromboplastin Times (aPTT) > 1.5 × upper
limit of normal (ULN)
2. Total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic
pyruvic transaminase (SGPT), alkaline phosphatase > 2.5 × ULN
3. Neutrophil count < 1000/µL
4. Hemoglobin < 9.0 g/dL
5. Creatinine > 1.2 x ULN
5. Previous history of neurological complications due to PV infection.
6. Not recovered from the toxic effects of prior chemo- and/or radiation therapy, if
applicable. Guidelines for this recovery period are dependent upon the specific
therapeutic agent received; the following are excluded relative to planned PVSRIPO
treatment:
1. Tumor treating fields: = 1 week
2. Chemotherapy or bevacizumab: = 4 weeks (except for nitrosourea and lomustine: = 6
weeks)
3. Metronomic dosed chemotherapy, such as daily temozolomide, etoposide or
cyclophosphamide: = 1 week
7. Prior, unrelated malignancy deemed unstable by the Investigator, except for cervical
carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the
skin.
8. May not have received immunotherapy = 4 weeks prior to PVSRIPO treatment unless the
subject has recovered from side effects of such therapy, as determined by the
Investigator.
9. 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.
10. Evidence of diffuse subependymal or leptomeningeal disease or tumor in the brainstem,
cerebellum, or spinal cord.
11. Undetectable anti-tetanus toxoid immunoglobulin G (IgG) (except for retreatment). If
undetectable, a tetanus booster will be required at least 1 week, but less than 6
weeks, prior to administration of PVSRIPO.
12. Known history of agammaglobulinemia.
13. On = 4 mg/day of dexamethasone within the 2 weeks prior to admission for PVSRIPO
infusion.
14. Worsening steroid myopathy (history of gradual progression of bilateral proximal
muscle weakness, and atrophy of proximal muscle groups).
15. Concomitant disease, condition, or disorder that deems the subject unsuitable for
treatment with PVSRIPO in the opinion of the Investigator.
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