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Trial record 1 of 1 for:    NCT02986178
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PVSRIPO in Recurrent Malignant Glioma

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02986178
Recruitment Status : Active, not recruiting
First Posted : December 8, 2016
Last Update Posted : June 18, 2020
Sponsor:
Collaborator:
Duke University
Information provided by (Responsible Party):
Istari Oncology, Inc.

Tracking Information
First Submitted Date  ICMJE December 6, 2016
First Posted Date  ICMJE December 8, 2016
Last Update Posted Date June 18, 2020
Actual Study Start Date  ICMJE June 1, 2017
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • Objective Radiographic Response Rate [ Time Frame: 24 months after initial PVSRIPO infusion and through study completion. ]
    Assess objective anti-tumor response based on iRANO criteria.
  • Objective Radiographic Response Rate [ Time Frame: 36 months after initial PVSRIPO infusion and through study completion. ]
    Assess objective anti-tumor response based on iRANO criteria.
  • Duration of Objective Radiographic Response [ Time Frame: 24 months after initial PVSRIPO infusion and through study completion. ]
    Assess time of confirmed response to confirmed progressive disease/death.
  • Duration of Objective Radiographic Response [ Time Frame: 36 months after initial PVSRIPO infusion and through study completion. ]
    Assess time of confirmed response to confirmed progressive disease/death.
Original Primary Outcome Measures  ICMJE
 (submitted: December 6, 2016)
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 10, 2020)
  • Overall Survival [ Time Frame: 24 and 36 months after initial PVSRIPO infusion and through study completion. ]
    Overall Survival, relative to external control group(s)
  • Landmark Survival [ Time Frame: 24 and 36 months post-infusion and through study completion. ]
    Overall survival at 24 and 36 months and greater
  • Disease Control Rate Following PVSRIPO Infusion [ Time Frame: 24 and 36 months after initial PVSRIPO infusion and through study completion. ]
    The percentage of patients classified as non-progressive by radiographic response based on standard criteria.
  • Safety of PVSRIPO: proportion of patients who experience grade 3, 4, or 5 AEs [ Time Frame: While on study; average of 12 to 36 months after initial PVSRIPO infusion. ]
    Within each cohort for those randomized prior to protocol version 7, as well as for those patients retreated with PVSRIPO, the proportion of patients who experience grade 3, 4, or 5 AEs that are possibly, probably, and definitely related to protocol treatment will be estimated.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2016)
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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PVSRIPO in Recurrent Malignant Glioma
Official Title  ICMJE A Multicenter Phase 2 Study of Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) in Recurrent WHO Grade IV Malignant Glioma Patients
Brief Summary This is a phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma.
Detailed Description

This is a Phase 2 study of oncolytic polio/rhinovirus recombinant (PVSRIPO) in adult patients with recurrent World Health Organization (WHO) grade IV malignant glioma. The objective of this study is to investigate the safety and efficacy (anti-tumor response and survival) of PVSRIPO in recurrent WHO grade IV malignant glioma.

Patients will be administered PVSRIPO intratumorally via convection-enhanced delivery (CED) using an intracerebral catheter placed within the enhancing portion of the tumor. Retreatment with PVSRIPO is allowed, provided retreatment eligibility criteria are met.

All patients who receive PVSRIPO treatment will be included in efficacy and safety analyses.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Glioma
Intervention  ICMJE Biological: PVSRIPO
A single dose of an oncolytic polio/rhinovirus recombinant (PVSRIPO)
Study Arms  ICMJE Experimental: Polio/Rhinovirus Recombinant (PVSRIPO)
Polio/Rhinovirus Recombinant (PVSRIPO)
Intervention: Biological: PVSRIPO
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 10, 2020)
122
Original Estimated Enrollment  ICMJE
 (submitted: December 6, 2016)
62
Estimated Study Completion Date  ICMJE December 2023
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

INCLUSION CRITERIA SUMMARY:

  1. Patients must have a recurrent (first or second recurrence only, including this recurrence; transformation from a lower grade tumor to a WHO grade IV malignant glioma will be considered a first recurrence) supratentorial WHO grade IV malignant glioma based on imaging studies with measurable disease (a minimum measurement of 1 cm and maximum of 5.5 cm of contrast-enhancing tumor) with prior histopathology consistent with a WHO grade IV malignant glioma confirmed by the site's neuropathologist or the neuropathologist's designate.
  2. Male patients who are sexually active are eligible if he and/or his partner(s) meets the criteria outlined in the protocol. Female subjects are eligible if he and/or his partner(s) meets the criteria outlined in the protocol.
  3. Age ≥ 18 years of age.
  4. Karnofsky Performance Status (KPS) Score ≥ 70%.
  5. Prothrombin and Partial Thromboplastin Times ≤ 1.2 x normal prior to biopsy.
  6. Total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase ≤ 2.5 x normal prior to biopsy.
  7. Neutrophil count ≥ 1000 prior to biopsy.
  8. Hemoglobin ≥ 9 prior to biopsy.
  9. Platelet count ≥ 100,000/μL unsupported is necessary for eligibility on study; however, because of risks of intracranial hemorrhage with catheter placement, platelet count ≥ 125,000/μL is required for the patient to undergo biopsy and catheter insertion, which can be attained with the help of platelet transfusion.
  10. Creatinine ≤ 1.2 x normal range prior to biopsy.
  11. Positive serum anti-PV titer prior to biopsy.
  12. The patient must have received a boost immunization with trivalent inactivated IPOL™ (Sanofi-Pasteur) at least 1 week, but less than 6 weeks, prior to administration of the study agent.
  13. At the time of biopsy, prior to administration of virus, the presence of recurrent tumor must be confirmed by histopathological analysis.
  14. A signed IRB-approve informed consent form (ICF).
  15. Able to undergo brain MRI with and without contrast.

EXCLUSION CRITERIA SUMMARY:

  1. Females who are pregnant or breast-feeding.
  2. Patients with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons, their designate, and the reviewer designated by the sponsor.
  3. Patients with severe, active co-morbidity, defined as in the protocol.
  4. Patients with a previous history of neurological complications due to PV infection.
  5. 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.
  6. Patients may not have received tumor treating fields (≤ 1 week), chemotherapy or bevacizumab ≤ 4 weeks [except for nitrosourea and lomustine (≤ 6 weeks); metronomic dosed chemotherapy, such as daily temozolomide, etoposide or cyclophosphamide (≤ 1 week)] prior to starting the study drug.
  7. Patients may not have received immunotherapy ≤ 4 weeks prior to starting the study drug unless patients have recovered from side effects of such therapy.
  8. Patients may not be less than 12 weeks from radiation therapy of the brain, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation.
  9. Prior to enrollment, has not completed all standard of care treatments, including surgical procedure and radiation therapy (at least 59Gy) as outlined in the protocol.
  10. Patients with neoplastic lesions in the brainstem, cerebellum, or spinal cord; radiological evidence of multiple areas of active (growing) disease (active multifocal disease); tumors with contrast-enhancing tumor component crossing the midline (crossing the corpus callosum); extensive subependymal disease (tumor touching subependymal space is allowed); or extensive leptomeningeal disease (tumor touching leptomeninges is allowed).
  11. Patients with undetectable anti-tetanus toxoid immunoglobulin G (IgG).
  12. Patients with known history of agammaglobulinemia.
  13. Patients on greater than 4 mg per day of dexamethasone within the 2 weeks prior to admission for PVSRIPO infusion.
  14. Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups).
  15. 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.
  16. For patients randomized prior to V7, a known history of hypersensitivity to lomustine, dacarbazine, or any components of lomustine.
  17. Patients with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02986178
Other Study ID Numbers  ICMJE Pro00077024
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Istari Oncology, Inc.
Study Sponsor  ICMJE Istari Oncology, Inc.
Collaborators  ICMJE Duke University
Investigators  ICMJE
Principal Investigator: Dina Randazzo, DO Duke University
PRS Account Istari Oncology, Inc.
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP