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Phase 1b Study PVSRIPO for Recurrent Malignant Glioma in Children

This study is currently recruiting participants.
Verified November 2017 by Duke University
Sponsor:
ClinicalTrials.gov Identifier:
NCT03043391
First Posted: February 6, 2017
Last Update Posted: December 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
Solving Kids’ Cancer
Musella Foundation for Brain Tumor Research & Information, Inc.
The Andrew McDonough B+ Foundation
Istari Oncology, Inc.
Information provided by (Responsible Party):
Duke University
  Purpose
The purpose of the study is to confirm the safety of the selected dose and potential toxicity of oncolytic poliovirus (PV) immunotherapy with PVSRIPO for pediatric patients with recurrent WHO grade III or IV malignant glioma, but evidence for efficacy will also be sought. The primary objective is to confirm the safety of the selected dose of PVSRIPO when delivered intracerebrally by convection-enhanced delivery (CED) in children with recurrent WHO Grade III malignant glioma (anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, anaplastic pleomorphic xanthoastrocytoma) or WHO Grade IV malignant glioma (glioblastoma, gliosarcoma). A secondary objective is to estimate overall survival (OS) in this population.

Condition Intervention Phase
Malignant Glioma Anaplastic Astrocytoma Anaplastic Oligoastrocytoma Anaplastic Oligodendroglioma Glioblastoma Gliosarcoma Biological: Polio/Rhinovirus Recombinant (PVSRIPO) Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:
Phase Ib study to evaluate feasibility, safety, and preliminary evidence of efficacy of the optimal adult dose in a pediatric population
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Study of Oncolytic Polio/Rhinovirus Recombinant Against Recurrent Malignant Glioma in Children

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Percentage of participants with unacceptable toxicity [ Time Frame: 14 days after treatment with PVSRIPO ]
    Percentage of participants with unacceptable toxicity during the 14-day period post-PVSRIPO treatment


Secondary Outcome Measures:
  • 24-month overall survival [ Time Frame: 24 months after administration of PVSRIPO ]
    The percentage of participants alive at 24 months after the administration of PVSRIPO. Overall survival is defined as the time from the date of administration of PVSRIPO until the date of death, or the date of last follow-up if alive. Kaplan-Meier methods will be used to estimate overall survival.


Estimated Enrollment: 12
Anticipated Study Start Date: December 2017
Estimated Study Completion Date: July 1, 2021
Estimated Primary Completion Date: July 1, 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Polio/Rhinovirus Recombinant (PVSRIPO)
PVSRIPO is an altered form of the live polio vaccine. It was produced by removing a piece of the virus and replacing it with a piece from a common cold virus. This was done to make sure PVSRIPO cannot cause polio even when injected into the brain.
Biological: Polio/Rhinovirus Recombinant (PVSRIPO)
PVSRIPO will be delivered intratumorally by convection-enhanced delivery (CED) using an intracerebral catheter placed within the enhancing portion of the tumor. A stereotactic biopsy will be performed prior to virus administration. Immediately following the stereotactically-guided tumor biopsy, a catheter will be implanted in the operating room at a site the same or different from that used for the biopsy using sterile techniques under general anesthesia. The entire volume of PVSRIPO to be delivered will be pre-loaded into a syringe by the investigational pharmacist and connected to the catheter under sterile conditions in the Pediatric Intensive Care Unit (PICU) just prior to beginning of infusion.

Detailed Description:
PVSRIPO will be delivered intratumorally by CED using an intracerebral catheter placed within the enhancing portion of the tumor. The population group are patients with recurrent WHO grade III or IV malignant glioma who are aged 12 through 18 years old. After a single dose of PVSRIPO, subjects will return for periodic visits to monitor tumor status, adverse events, and changes in blood immune profiles. A maximum of 12 pediatric patients will be treated with PVSRIPO, and then carefully monitored for safety for at least a year after treatment.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a recurrent supratentorial WHO Grade III malignant glioma (anaplastic astrocytoma, anaplastic oligoastrocytoma, anaplastic oligodendroglioma, anaplastic pleomorphic xanthoastrocytoma, ependymoma) or WHO Grade IV malignant glioma (glioblastoma, gliosarcoma) based on imaging studies with measurable disease (≥ 1 cm and ≤ 5.5 cm of contrast-enhancing tumor). The prior histopathology must be consistent with a World Health Organization (WHO) Grade III or IV malignant glioma confirmed by the study pathologist, Roger McLendon, or his designee. There is no standard of care treatment for children with Grade III/IV gliomas. Patients must have completed first-line treatments including surgical procedure and a minimum of 54 Gray of radiation prior to participating in this trial.
  • Due to the potential implications of the treatment on the developing CNS, all patients must be ≥ 12 years of age and ≤ 18 years of age at the time of entry into the study.
  • The patient must have a Lansky or Karnofsky Performance Score (KPS) of ≥ 70% at the time of entry.
  • Laboratory Studies:
  • Platelet count ≥ 125,000 per microliter prior to biopsy (unsupported). Platelets ≥ 100,000 per microliter prior to infusion (unsupported);
  • Prothrombin and Partial Thromboplastin Times ≤ 1.2 x upper limit of normal (ULN) prior to biopsy;
  • Positive serum anti-poliovirus titer ≥ 1:8 prior to biopsy;
  • Creatinine ≤ 1.2 x ULN prior to biopsy;
  • Total bilirubin, AST, ALT, alkaline phosphatase ≤ 2.5 x ULN prior to biopsy;
  • Neutrophil count ≥ 1000 per microliter prior to biopsy (unsupported);
  • Hemoglobin ≥ 9 gm/dl prior to biopsy (can be transfused).
  • The patient must have received a boost immunization with trivalent inactivated IPOL™ (Sanofi-Pasteur) ≥ 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 (if 18 years old) or their parent(s) or guardian(s) 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. All children will have to provide assent to the study.
  • Able to undergo brain MRI with and without contrast without requiring general anesthesia.

Exclusion Criteria:

  • Pregnant or breast-feeding. Female patients of child-bearing potential or female sexual partners (who are of child-bearing potential) of male patients must use at least one of the following methods of medically acceptable contraceptives: approved hormonal contraceptives (such as birth control pills, patches, implants or infusions), an intrauterine device (IUD), or a barrier method of contraception (such as a condom or diaphragm) used ith spermicide. Because all patients are required to have a boost immunization of trivalent inactivated IPOL™, there should be no risk of transmission of a mother to her fetus after receiving intracranial PVSRIPO. As such, patients who become pregnant after receiving PVSRIPO will continue to be monitored in the same manner, i.e. per protocol, unless the assessment is contra-indicated during pregnancy. Partners who become pregnant will sign a Pregnant Partner Information Form and information regarding the pregnancy and its outcome may be collected.
  • Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeon.
  • Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5°F).
  • Patients with known immunosuppressive disease or known human immunodeficiency virus infection.
  • Patients with unstable or severe intercurrent medical conditions such as severe heart (New York Heart Association Class 3 or 4) or lung (FEV1 < 50%) disease, uncontrolled diabetes mellitus.
  • Patients with albumin allergy.
  • Gadolinium allergy.
  • A history of neurological complications due to past PV 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.
  • Patients who have not recovered from the toxic effects of prior chemo- and/or radiation therapy. Guidelines for this recovery period are dependent upon the specific therapeutic agent being used:
  • Patients who are less than 12 weeks from radiation therapy, unless progressive disease outside of the radiation field or 2 consecutive scans with disease progression or histopathologic confirmation of recurrent tumor.
  • Patients who 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 who have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy.
  • Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord, tumors extending into or crossing the corpus callosum, intraventricular tumors, pineal tumors, pituitary tumors, radiological evidence of active (growing) multifocal disease, leptomeningeal disease, or other locations at the discretion of the treating neurosurgeon.
  • Patients with a diagnosis of agammaglobulinemia, that is:
  • Undetectable anti-tetanus toxoid IgG
  • Known history of agammaglobulinemia
  • Patients who are on dexamethasone receiving > 4 mg/day in the two weeks prior to admission for intra-cerebral delivery of PVSRIPO.
  • 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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03043391


Contacts
Contact: David Ashley, MBBS, FRACP, PhD 919-684-0000 david.ashley@duke.edu
Contact: Eric Thompson, MD 919-684-0000 eric.thompson@duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: David Ashley, MBBS, FRACP, PhD    919-684-0000    david.ashley@duke.edu   
Contact: Eric Thompson, MD    919-684-0000    eric.thompson@duke.edu   
Principal Investigator: David Ashley, MBBS, FRACP, PhD         
Principal Investigator: Eric Thompson, MD         
Sponsors and Collaborators
Duke University
Solving Kids’ Cancer
Musella Foundation for Brain Tumor Research & Information, Inc.
The Andrew McDonough B+ Foundation
Istari Oncology, Inc.
Investigators
Study Director: Darell Bigner, MD, PhD Istari Oncology, Inc.
Principal Investigator: David Ashley, MBBS, FRACP, PhD Duke University
Principal Investigator: Eric Thompson, MD Duke University
  More Information

Additional Information:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT03043391     History of Changes
Other Study ID Numbers: Pro00071228
First Submitted: February 2, 2017
First Posted: February 6, 2017
Last Update Posted: December 5, 2017
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Duke University:
Pediatric Malignant Glioma
PVSRIPO
Pro00071228
Eric Thompson
Darell Bigner
Oncolytic Poliovirus
David Ashley

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Gliosarcoma
Oligodendroglioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue