| Eligibility |
Inclusion Criteria:
1. Age >18 years of age
2. Disease recurrence of at least 1x1cm and a maximum of 3x3cm of enhancing tumor:
Dose escalation portion: patients with recurrent high-grade glioma, IDH wt or IDH
mutated, grade 3 or grade 4 based on imaging.
Dose expansion portion: Recurrent, IDH wt, glioblastoma, WHO grade 4. Diagnosis has be
made using the 2021 WHO Classification of Tumors of the CNS.
3. The neurosurgeon must confirm (a) the tumor location (> 1 cm from eloquent brain), (b)
that the placement of infusion catheter within or through the progressive enhancing
tumor is feasible and is at a safe distance to eloquent brain function. These aspects
will be determined prior catheter placement on the basis of prior (screening) MRI and
then at the time of catheter placement on the basis of a CT scan prior to infusion.
The tip of the catheter must be placed as follows:
1. Within the enhancing portion or in the vicinity of enhancement of target lesion
(i.e., infiltrative disease)
2. = 0.5 cm from ventricles
3. = 1 cm deep into the brain
4. = 0.5 cm from the corpus callosum
4. If a histological or pathological confirmation of recurrence (< 6 weeks) is not
available, a pre-infusion biopsy will be required to confirm recurrence.
5. Adequate pulmonary function, with a baseline pulse oximetry of at 90% on room air.
6. The subject must have received standard radiation therapy plus temozolomide and be
refractory to radiation therapy plus temozolomide prior to enrollment.
7. Prior to administration of MVR-C5252, the presence of recurrent tumor must be
confirmed by histopathological analysis. (Distinguishing between recurrent active
tumor and radiation necrosis is important to avoid delivering MVR-C5252 when there is
no active disease).
Should participants have further surgical resection at any time following their
participation in the study, patients will be invited to make any biospecimens
available for correlative research.
8. Karnofsky Performance Status (KPS) = 70%
9. Labs:
1. platelets = 100,000 unsupported at initial screening, but = 125,000 supported
prior to biopsy/catheter insertion
2. hemoglobin = 9 gm/dL, ANC = 1000/µL
3. creatinine = 1.5x upper limit of normal (ULN)
4. total bilirubin = 1.5 x ULN, AST/ALT = 2.5 x ULN (subjects with known or
suspected Gilbert's syndrome are excluded if total bilirubin > 3.0 x ULN or
direct bilirubin > 1.5 x ULN)
5. PT, aPTT = 1.2 x ULN prior to biopsy (if patient is taking warfarin, INR should
be obtained and be < 2.0)
10. Able to undergo MRI brain with and without contrast
11. If the patient is a sexually active female of childbearing potential, whose partner is
male, or if the patient is a sexually active male, whose partner is a female of child
bearing potential, the patient must use appropriate contraceptive measures for the
duration of the treatment and for 6 months afterwards. Female patients of childbearing
potential must have a negative serum pregnancy test at the time of screening and
within 48 hours of starting the MVR-C5252 infusion.
12. Signed informed consent approved by the Institutional Review Board
Exclusion Criteria:
1. 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
2. Patients who are pregnant or breastfeeding
3. Patients with contrast-enhancing tumor crossing the midline, multifocal tumor,
infratentorial tumor, tumor in eloquent brain regions, extensive tumor dissemination
(subependymal or leptomeningeal), or in unsafe brain regions per the opinion of the
treating neurosurgeon
4. Unstable systemic disease in the opinion of the treating physician.
5. Active infection requiring systemic therapy or causing fever (temperature > 38.1°C) or
subjects with unexplained fever (temperature > 38.1°C) within 7 days prior to the day
of investigational product administration.
6. Patients on >4 mg per day of dexamethasone within the 2 weeks prior to admission for
MVR-C5252 infusion or systemic therapy with immunosuppressive agents within 28 days
prior to admission for MVR-C5252 infusion
7. Patients who have not completed standard of care treatment prior to participation in
this trial
8. Less than 12 weeks from radiation therapy, unless progressive disease outside of the
radiation field or 2 progressive scans at least 4 weeks apart or histopathologic
confirmation of recurrent tumor
9. Treated with immunotherapeutic agents prior to MVR-C5252 treatment, within 4 weeks,
alkylating agents within 4 weeks, nitrosoureas within 6 weeks, or non-alkylating
chemotherapy within 2 weeks before enrollment, unless the patient has recovered from
the expected toxic effects of such therapy
10. Treated with antiangiogenic agents (i.e., bevacizumab) within 4 weeks before biopsy
11. Patients who require an attenuated or live vaccine within 28 days prior to the first
trial drug administration and during the study treatment period
12. Prior treatment with any oncolytic virus, cell therapy or gene therapy.
13. Prior antitumor treatment with intracranial implants, such as Carmustine
14. Previous history of allergic reactions to similar biological components such as HSV-1,
IL-12 or anti-PD-1 antibodies, or with known allergic reactions to any component of
the MVR-C5252 prescription, including glycerol.
15. Systemic use (other than topical) of anti-HSV drugs (including, but not limited to,
acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir,
etc.)
16. Patients with cardiac risks including congestive heart failure (as defined by New York
Heart Association Functional Classification III or IV), unstable angina, serious
uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to
study entry, or a history of myocarditis.
|
