Combination of PVSRIPO and Atezolizumab for Adults With Recurrent Malignant Glioma

NCT03973879 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: Pro00100677
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluates the safety of PVSRIPO treatment in combination with Atezolizumab in patients with WHO grade IV malignant glioma. All patients will receive a single PVSRIPO infusion followed by atezolizumab infusions every three weeks for up to two years.

Conditions

Malignant Glioma

Keywords

PVSRIPO; Atezolizumab; Glioblastoma; Glioma; Bigner; Randazzo; Brain tumor; Duke; Istari; Pro00100677; Genentech

Outcome Measures

Primary Outcomes (2)

• Number of unacceptable adverse events

  Any Grade 3 or any Grade 4 toxicity that is not reversible within 2 weeks, or any life-threatening event, or treatment-related death.

  14 days after first atezolizumab treatment

• Proportion of patients alive

  Proportion of patients alive at 24 months after PVSRIPO infusion

  24 months after PVSRIPO infusion

Study Arms (1)

PVSRIPO + Atezolizumab

EXPERIMENTAL

Single PVSRIPO infusion at a dose of 5x10\^7 tissue culture infected dose (TCID50). Atezolizumab infusions at a dose of 1200 mg every three weeks for up to two years.

Biological: PVSRIPO; Drug: Atezolizumab

Interventions

PVSRIPO BIOLOGICAL

Oncolytic polio/rhinovirus recombinant

PVSRIPO + Atezolizumab

Atezolizumab DRUG

Antibody

Also known as: Tecentriq

PVSRIPO + Atezolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 WHO grade IV malignant glioma confirmed by the study pathologist, Roger McLendon, or his designate. Assuming patient meets all other criteria, the treating neurosurgeon must confirm placement of infusion catheter tip can occur ≥ 1cm from ventricles and that procedures can be completed per their medical judgement and in keeping with the protocol, when considering individual lesion characteristics including location relative to eloquent brain function.
• Patient or partner(s) meets one of the following criteria:
• Non-childbearing potential (i.e. not sexually active, physiologically incapable of becoming pregnant, including any female who is post-menopausal or surgically sterile, or any male who has had a vasectomy). 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
• Childbearing potential 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.
• 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 ≥ 100,000/µl unsupported is necessary for eligibility on the study; however, because of risks of intracranial hemorrhage with catheter placement, platelet count ≥ 120,000/µl is required for the patient to undergo biopsy and catheter insertion, which can be attained with the help of platelet transfusion
• 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, but less than 6 weeks, 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

You may not qualify if:

• Females who are pregnant or breast-feeding
• 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 intravenous 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 unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4)
• Patients with known lung (forced expiratory volume in the first second of expiration (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 PV 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 of the brain, 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 for recurrent glioma, including surgical procedure and radiation therapy (at least 59 Gy)

Sponsors & Collaborators

• Darell Bigner: lead
• Istari Oncology, Inc.: collaborator
• Genentech, Inc.: collaborator

Related Links

• The Preston Robert Tisch Brain Tumor Center
• Duke Health

MeSH Terms

Conditions

Glioma; Glioblastoma; Brain Neoplasms

Interventions

atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Darell D Bigner, MD, PhD

  Istari Oncology, Inc.

  STUDY DIRECTOR

• Dina M Randazzo, DO

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: May 31, 2019
• First Posted: June 4, 2019
• Study Start: February 1, 2020
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: February 11, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share