Recombinant Oncolytic Poliovirus PVS-RIPO in Treating Patients with Recurrent Grade IV Malignant Glioma
Basic Trial Information
|Phase I||Biomarker/Laboratory analysis, Treatment||Active||18 and over||Pro00031169|
NCI-2013-01899, PVSRIPO, NS20023, NCT01491893
This phase I trial studies the side effects and best dose of recombinant oncolytic poliovirus PVS-RIPO in treating patients with grade IV malignant glioma that has come back. Vaccines made from a gene-modified virus may help the body build an effective immune response to kill tumor cells.
Further Study Information
I. To determine the maximally tolerated dose (MTD) and phase II dose of PVSRIPO (recombinant oncolytic poliovirus PVS-RIPO) when delivered intracerebrally by convection-enhanced delivery.
I. To obtain correlative mechanistic evidence for PVSRIPO’s effects on infected World Health Organization (WHO) grade IV malignant glioma tumors and to estimate progression free survival (PFS) and overall survival (OS) in recurrent WHO grade IV malignant glioma patients.
II. To estimate the efficacy of PVSRIPO administered at the optimal dose.
I. Describe changes visualized on imaging due to intratumoral inoculation of PVSRIPO.
II. Evaluate parameters of general immune activation: frequency of immune cell subsets in peripheral blood and changes in serum levels of cytokines.
III. Evaluate CD8 and CD4 immunologic response against polio specific and glioblastoma multiforme (GBM) specific antigens to be determined.
IV. Identify genetic predictors of response or failure of response to treatment with PVSRIPO.
OUTLINE: This is a dose-escalation study.
Patients receive recombinant oncolytic poliovirus PVS-RIPO intratumorally over approximately 6.5 hours in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 2, 4, 8, 16, 24, 32, 40 and 48 weeks.
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 World Health Organization (WHO) grade IV malignant glioma confirmed by the study pathologist, Roger McLendon, or his designate
The patient must have a Karnofsky performance score (KPS) of >= 70% at the time of entry
Platelet count >= 125,000/ul prior to biopsy; platelets >= 100,000/ul prior to infusion
Prothrombin and partial thromboplastin times =< 1.2 x normal prior to biopsy
Positive serum anti-poliovirus titer prior to biopsy
Creatinine =< 1.2 x normal prior to biopsy
Total bilirubin =< 2.5 x normal prior to biopsy
Serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) =< 2.5 x normal prior to biopsy
Alkaline phosphatase =< 2.5 x normal prior to biopsy
Neutrophil count >= 1000 prior to biopsy
Hemoglobin >= 9 prior to biopsy
The patient must have received a boost immunization with trivalent inactivated poliovirus vaccine (IPOL) (Sanofi-Pasteur) at least 1 week 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 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
Able to undergo brain magnetic resonance imaging (MRI) with and without contrast
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 childbearing potential, must use a medically accepted birth control
Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons, Allan Friedman or John Sampson, or their designate, will be excluded
If patients meet any of the following they will be excluded:
Active infection requiring intravenous treatment or having an unexplained febrile illness (temperature maximum [Tmax] > 99.5 Fahrenheit [F]/37.5 Celsius [C])
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 (forced expiratory volume in 1 second [FEV1] < 50%) disease, uncontrolled diabetes mellitus
Albumin allergy; patients with a known allergy will be excluded
A history of neurological complications due to poliovirus infection
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 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 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 status is unknown at the 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) multifocal disease, or leptomeningeal disease will be excluded; patients with evidence of diffuse subependymal disease or tumor in the brainstem, cerebellum, spinal cord, or cerebrospinal fluid (CSF) will also be excluded
Patients with radiological evidence of active (growing) multifocal disease, tumors extending into or crossing the corpus callosum or leptomeningeal disease, will be excluded
Patients must not have diagnosis of agammaglobulinemia; patients with the following will be excluded:
Undetectable anti-tetanus toxoid IgG
Known history of agammaglobulinemia
Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to admission for PVSRIPO 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
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
Duke University Medical Center
- National Cancer Institute
Duke University Medical Center
Dina M. Randazzo
Dina M. Randazzo
Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01491893
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