Recombinant Oncolytic Poliovirus PVS-RIPO in Treating Patients with Recurrent Grade IV Malignant Glioma
Basic Trial Information
|Phase I||Biomarker/Laboratory analysis, Treatment||18 and over||Pro00031169|
NCI-2013-01899, 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) or optimal 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 obtain information about clinical response rates to intratumoral inoculation of PVSRIPO.
III. To estimate the efficacy of PVSRIPO administered at the optimal dose.
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.
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
At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis of frozen sections
The patient must have received a boost immunization with trivalent inactivated IPOL™ (poliovirus vaccine inactivated) (Sanofi-Pasteur) at least 2 weeks prior to administration of the study agent
Hemoglobin >= 9
Neutrophil count >= 1000
Alkaline phosphatase =< 2.5 x normal
Serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) =< 2.5 x normal
Total bilirubin =< 2.5 x normal
Positive serum anti-poliovirus titer
Prothrombin and partial thromboplastin times =< 1.2 x normal
Platelet count >= 125,000/ul
The patient must have a Karnofsky performance score (KPS) of >= 70% at the time of entry
Patients may be included in the study independent of the regimen of previous surgical, radiation, or chemotherapy treatments administered; however, the exclusions listed below must be followed
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
Creatinine =< 1.2 x normal
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 worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to PVSRIPO infusion
Patients must not have diagnosis of agammaglobulinemia; patients with the following will be excluded:
Immunoglobulin G (IgG) levels < 400 mg/dL (4 g/L)
Undetectable anti-tetanus toxoid IgG
Known history of agammaglobulinemia
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 cerebrospinal fluid (CSF) will 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 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 have received investigational drugs =< 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy
Patients must have completed all standard of care treatments including resection and concurrent chemo-radiation prior to participating in this trial
A history of neurological complications due to poliovirus infection
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
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 two forms of IRB approved birth control; one method must be a barrier method
Sexually active men, whose partner is a female of child bearing potential, must use a barrier method of contraception and either have had a vasectomy or use spermicide
If patients meet any of the following they will be excluded:
Active infection requiring 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 lung (forced expiratory volume in 1 second [FEV1] < 50%) disease, uncontrolled diabetes mellitus
Albumin allergy; patients with a known allergy will be excluded
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
Duke University Medical Center
- National Cancer Institute
Duke University Medical Center
Allan Howard Friedman
Allan Howard Friedman
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01491893
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.