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PVSRIPO in Recurrent Malignant Glioma

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ClinicalTrials.gov Identifier: NCT02986178
Recruitment Status : Recruiting
First Posted : December 8, 2016
Last Update Posted : March 19, 2019
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 March 19, 2019
Actual Study Start Date  ICMJE June 1, 2017
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Current 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02986178 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2019)
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.
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
 (submitted: March 15, 2019)
  • The changes visualized on imaging due to intratumoral inoculation of PVSRIPO will be assessed [ Time Frame: Up to week 52 ]
    The components of the inflammatory reaction will be summarized
  • Assessment of immunologic changes stemming from the administration of PVSRIPO alone or in combination with lomustine utilizing peripheral blood samples collected at defined intervals. [ Time Frame: Up to 24 months ]
    Peripheral blood will be collected at defined intervals for correlative immune-monitoring study.
  • Assessment of tumor genetic markers as possible predictors of response. [ Time Frame: Up to 24 months ]
    The Cox model will explore the impact of various genetic tumor markers on survival time.
  • Assessment of quantitative gut microbiome profile. [ Time Frame: Up to 24 months ]
    Utilizing stool samples, the quantitative gut microbiome profile will be assessed before and after PVSRIPO for quantitive gut profile analysis
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 primary objective of this study is to assess the efficacy of a single dose of PVSRIPO among adults with WHO grade IV malignant glioma at first or second recurrence relative to the survival observed in a historical control group. The secondary objective is to determine the safety of PVSRIPO treatment in recurrent WHO grade IV malignant glioma patients. 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. Subjects will be receive PVSRIPO alone to evaluate the impact of the 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. Based on experience with a Phase 1 study at Duke, previously published reports, and institutional review board (IRB)- and FDA-approved trials using similar infusion techniques, patients will be infused at a rate of 0.5 mL/hr. A Medfusion™ 3500 infusion pump (Smiths Medical, Minneapolis, MN) or any other comparable FDA-cleared syringe infusion pump approved by the sponsor or their designee, will be pre-programmed to a delivery rate of 0.5 mL/hr. The target accrual for the study is 102 patients. All patients who are randomized and receive PVSRIPO treatment will be included in efficacy and safety analyses.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE 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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 10, 2019)
102
Original Estimated Enrollment  ICMJE
 (submitted: December 6, 2016)
62
Estimated Study Completion Date  ICMJE May 2023
Estimated Primary Completion Date May 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  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). Tumor size and location requirements will need to be confirmed by the reviewer designated by the Sponsor. Prior histopathology consistent with a WHO grade IV malignant glioma confirmed by the site's neuropathologist or the neuropathologist's designate

    1. Assuming patient meets all other criteria, site neurosurgeon must confirm placement of infusion catheter tip can occur ≥ 1cm from ventricles and at a safe distance relative to eloquent brain function.
    2. Tumor size and location requirements per protocol must be confirmed as qualifying and safe to proceed by the reviewer(s) designated by the Sponsor.
  2. If the subject is male and sexually active, he is eligible to enter and participate in this study if his partner(s) meets the criteria outlined in 2a or if he or his partner(s) is using one of the methods of birth control outlined in 2b. If the subject is female, she is eligible to enter and participate in this study if she meets the following criteria:

    1. Non-childbearing potential (i.e. physiologically incapable of becoming pregnant, including any female who is postmenopausal or surgically sterile). Surgically sterile females are defined as those with a documented hysterectomy and/or bilateral oophorectomy or tubal ligation. Postmenopausal for purposes of this study, is defined as 1 year without menses); or
    2. Childbearing potential, has a negative serum pregnancy test at screening, and agrees to use one of the following methods of birth control: approved hormonal contraceptives (e.g. birth control pills, patches, implants, or infusions), an intrauterine device, or a barrier method of contraception (e.g. a condom or diaphragm) used with spermicide.
    3. If the male has had a vasectomy or is using a condom with spermicide, the female partner does not need to use additional birth control noted in 2a and 2b.
  3. Age ≥ 18 years of age at the time of entry into the study
  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 informed consent form (ICF) approved by the IRB will be required for patient enrollment into the study. Patients or their legally authorized representative (LAR) 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
  15. Able to undergo brain MRI with and without contrast

Exclusion Criteria

  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 follow:

    1. Patients with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax > 99.5°F/37.5°C)
    2. Patients with known immunosuppressive disease or known human immunodeficiency virus infection
    3. Patients with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
    4. Patients with known lung (forced expiratory volume in the first second of expiration [FEV1] < 50%) disease or uncontrolled diabetes mellitus
    5. Patients with albumin allergy
    6. Patients with gadolinium allergy
  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, unless progressive disease outside of the radiation field or 2 progressive scans at least 4 weeks apart or histopathologic confirmation
  9. Patients who have not completed all standard of care treatments, including surgical procedure and radiation therapy (at least 59Gy)

    1. 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
    2. 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
  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. 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: Heny Friedman, MD 919-681-3138 hfriedman@istarioncology.com
Contact: Andrea True Kelly, PhD 919-943-5023 atkelly@istarioncology.com
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: Undecided
Responsible Party Istari Oncology, Inc.
Study Sponsor  ICMJE Istari Oncology, Inc.
Collaborators  ICMJE Duke University
Investigators  ICMJE
Principal Investigator: Dina Randazzo, DO Duke University
Study Director: Darell Bigner, MD, PhD Istari Oncology, Inc.
PRS Account Istari Oncology, Inc.
Verification Date March 2019

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