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PVSRIPO With/Without Lomustine

This study is currently recruiting participants.
Verified November 2017 by Duke University
Sponsor:
ClinicalTrials.gov Identifier:
NCT02986178
First Posted: December 8, 2016
Last Update Posted: November 6, 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:
Istari Oncology, Inc.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Duke University
  Purpose
This is a randomized phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) alone or in combination with the chemotherapy drug lomustine in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke.

Condition Intervention Phase
Malignant Glioma Biological: PVSRIPO Drug: Lomustine Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Phase 2 Study of Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) Alone or in Combination With Lomustine in Recurrent WHO Grade IV Malignant Glioma Patients

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary 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 calculated from the date of administration of PVSRIPO until the date of death, or the date of last follow-up if alive. Kaplan-Meier methods are used to estimate overall survival.


Secondary Outcome Measures:
  • Percentage of participants with grade 3, 4, or 5 treatment-related adverse events [ Time Frame: Up to 24 months; events will be assessed continuously from the time of catheter placement for PVSRIPO administration until 30 days after a participant goes off study. ]
    The percentage of particpants with grade 3, 4 or 5 adverse events possibly, probably or definitely related to administration of PVSRIPO or Lomustine.


Estimated Enrollment: 62
Actual Study Start Date: June 1, 2017
Estimated Study Completion Date: May 2023
Estimated Primary Completion Date: May 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Polio/Rhinovirus Recombinant (PVSRIPO)
Polio/Rhinovirus Recombinant (PVSRIPO)
Biological: PVSRIPO
A single dose of an oncolytic polio/rhinovirus recombinant (PVSRIPO)
Experimental: Polio/Rhinovirus Recombinant (PVSRIPO) + Lomustine
Polio/Rhinovirus Recombinant (PVSRIPO) + Lomustine
Biological: PVSRIPO
A single dose of an oncolytic polio/rhinovirus recombinant (PVSRIPO)
Drug: Lomustine
A single oral dose of 110 mg/m2 lomustine 8 weeks after PVSRIPO administration. If a subject has been treated with bevacizumab in the time since PVSRIPO infusion, the lomustine dose will be dispensed as an oral therapy at 90 mg/m2 one time 8 weeks after PVSRIPO infusion.
Other Name: Gleostine

Detailed Description:
This is a randomized phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) alone or in combination with the chemotherapy drug lomustine in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma at the Preston Robert Tisch Brain Tumor Center (PRTBTC) at Duke. The primary objective of this study is to assess the survival of subjects receiving PVSRIPO with or without a single dose of lomustine relative to the survival observed in a historical control group. The secondary objective is to assess the safety of PVSRIPO in combination with lomustine. Subjects will be randomized to receive either PVSRIPO alone, or PVSRIPO in combination with a single dose of lomustine 8 weeks after PVSRIPO infusion, to evaluate the impact of these treatment regimens on 24-month survival relative to historical controls. PVSRIPO will be delivered intratumorally by convection-enhanced delivery (CED) using an intracerebral catheter placed within the enhancing portion of the tumor. Subjects randomized to the lomustine arm will receive a single oral dose of 110 mg/m2 lomustine 8 weeks after PVSRIPO administration. If a subject has been treated with bevacizumab in the time since PVSRIPO infusion, the lomustine dose will be dispensed as an oral therapy at 90 mg/m2 one time only 8 weeks after PVSRIPO infusion. The target accrual for the study is 62 patients, 31 patients per arm. All patients who are randomized and receive PVSRIPO treatment will be included in efficacy and safety analyses.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Age ≥ 18 years of age at the time of entry into the study.
  • Karnofsky Performance Score (KPS) ≥ 70%.
  • Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy.
  • Total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase ≤ 2.5 x normal prior to biopsy.
  • Neutrophil count ≥ 1000 prior to biopsy.
  • Hemoglobin ≥ 9 prior to biopsy.
  • Platelet count ≥ 125,000/µl prior to biopsy; Platelet count ≥ 100,000/µl prior to infusion.
  • Creatinine ≤ 1.2 x normal range prior to biopsy.
  • Positive serum anti-poliovirus titer prior to biopsy.
  • The patient must have received a boost immunization with trivalent inactivated 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 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 MRI with and without contrast.

Exclusion Criteria:

  • Females who are 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 with 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 neurosurgeons or their designate.
  • Patients with severe, active co-morbidity, defined as follow:

    • Patients with an active infection requiring treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C).
    • Patients with known immunosuppressive disease or known human immunodeficiency virus infection.
    • Patients with impaired cardiac function or clinically significant cardiac disease, such as congestive heart failure requiring treatment (New York Heart Association Class ≥ 2), uncontrolled hypertension or clinically significant arrhythmia; QTcF > 470 msec on electrocardiogram (ECG) if performed or congenital long QT syndrome; acute myocardial infarction or unstable angina pectoris < 3 months prior to study.
    • Patients with known lung (FEV1 < 50%) disease or uncontrolled diabetes mellitus.
    • Patients with albumin allergy.
    • Patients with gadolinium allergy.
  • Patients with a previous history of neurological complications due to poliovirus infection.
  • 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 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 who have not completed all standard of care treatments, including surgical procedure and radiation therapy (at least 59Gy).

    • If the MGMT (O(6)-methylguanine-DNA methyltransferase) 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 methylation status is unknown at 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, subependymal or leptomeningeal disease.
  • Patients with undetectable anti-tetanus toxoid IgG (Immunoglobulin G).
  • Patients with 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.
  • Patients with a known history of hypersensitivity to lomustine, dacarbazine, or any components of lomustine.
  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): NCT02986178


Contacts
Contact: David Ashley, MBBS, FRACP, PhD 919-684-5301 dukebrain1@dm.duke.edu
Contact: Stevie Threatt 919-684-5301 dukebrain1@dm.duke.edu

Locations
United States, North Carolina
Preston Robert Tisch Brain Tumor Center at Duke University Recruiting
Durham, North Carolina, United States, 27710
Contact: David Ashley, MBBS, FRACP, PhD    919-684-5301      
Contact: Stevie Threatt    919-684-5301      
Sponsors and Collaborators
Duke University
Istari Oncology, Inc.
National Cancer Institute (NCI)
Investigators
Principal Investigator: David Ashley, MBBS, FRACP, PhD Duke University
Study Director: Darell Bigner, MD, PhD Istari Oncology, Inc.
  More Information

Additional Information:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02986178     History of Changes
Other Study ID Numbers: Pro00077024
First Submitted: December 6, 2016
First Posted: December 8, 2016
Last Update Posted: November 6, 2017
Last Verified: November 2017

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

Keywords provided by Duke University:
Glioblastoma
Glioma
PVSRIPO
Duke
Pro00077024
Ashley
Brain tumor
Bigner

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Lomustine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents