Safety and Efficacy Study of REOLYSIN® in the Treatment of Recurrent Malignant Gliomas

September 30, 2014 updated by: Oncolytics Biotech

A Phase I/II Clinical Trial to Evaluate Dose Limiting Toxicity and Efficacy of Intralesional Administration of REOLYSIN® for the Treatment of Patients With Histologically Confirmed Recurrent Malignant Gliomas

RATIONALE: Oncolytic viruses such as reovirus (REOLYSIN®) can specifically kill tumor cells while leaving healthy cells unharmed.

PURPOSE: This phase I/II study investigates the maximum tolerated dose (MTD), dose limiting toxicity (DLT) and anti-tumor effect of intralesional administration of REOLYSIN® therapeutic reovirus in patients with malignant glioma with evaluable disease which is progressive/recurrent despite surgery and/or radiotherapy with or without chemotherapy. (The phase I portion of the study is currently enrolling patients.)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Oncolytic viruses, such as reovirus, are those viruses which specifically destroy cancer cells. Reovirus is a common virus that does not cause disease, and has been shown to be associated with only minor flu-like symptoms. REOLYSIN® is a formulation of the live, replication-competent wild-type reovirus that selectively replicates in tumor cells, while leaving healthy cells unharmed.

This phase I/II multi-center study follows a standard design utilizing therapeutic viral dosage escalation. The phase I portion of the trial will evaluate the doses of intralesional REOLYSIN titrated to a maximum tolerated dose (MTD). The objective of the phase II portion of the study is to assess tumor response. The proportion of patients surviving to six months and the safety of REOLYSIN® are secondary objectives.

Each patient enrolled in the study will receive a single infusion of REOLYSIN® over 72 hours. Patients will remain in hospital for at least 90 hours after initiation of infusion. Following REOLYSIN® administration, each patient will be followed for at least 12 weeks (Phase I) and at least 6 months (Phase II) with regular evaluation visits (weekly and then monthly). Evaluations will include tumor measurements, serial neurologic exams and functional performance status assessments at baseline, prior to hospital discharge, and at weeks 4, 8, 12, 16 and 24 after REOLYSIN® therapy. Changes in performance will be assessed using the Karnofsky Performance Status scale. Subjects will also undergo serial blood sampling for evaluation of viral RNA, hematology and biochemistry.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • California
      • Los Angeles, California, United States, 90048
        • Cedars-Sinai Medical Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Medical Center and Arthur G. James Cancer Hospital and Richard J. Solove Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Abbreviated Inclusion Criteria:

  • PHASE I: 1st, 2nd or 3rd recurrence of: glioblastoma multiforme; gliosarcoma; anaplastic astrocytoma; anaplastic mixed glioma; or anaplastic oligodendroglioma
  • PHASE II: 1st recurrence of glioblastoma multiforme (only)
  • Progressing/recurrent lesion which is ≥1cmx1cm. For the Phase II study the lesion must be ≤5cmx5cm, defined by MRI only
  • Be fully recovered from any prior therapy
  • Have been treated at the time of original diagnosis by surgery and external beam radiation to a dose of at least 5000 cGy; radiotherapy completed at least 6 weeks before REOLYSIN® therapy
  • Any intracranial surgery, except for stereotactic needle biopsy, must have occurred at least 4 weeks before REOLYSIN® therapy
  • Any anti-cancer drug therapy must have been completed at least 4 weeks (6 weeks in the case of prior nitrosourea therapy) before REOLYSIN® therapy
  • Have a life expectancy of ≥8 weeks and a Karnofsky Performance Status (KPS) of ≥60
  • Absolute neutrophils ≥1.5 x10^9/L; hemoglobin ≥100g/L; platelets ≥100 x 10^9/L
  • ALT ≥1.5 x ULN; total bilirubin ≥1.5 x ULN
  • Serum creatinine ≤1.5 x ULN
  • EKG with no evidence of active, acute cardiovascular disease
  • PT within normal limit
  • Women of childbearing potential must have a negative pregnancy test
  • Reside or have suitable living arrangements within a reasonable geographical area of the study site and be able to participate in all follow-up visits
  • Patients requiring corticosteroids must be on a stable dose of steroid for at least two weeks prior to baseline MRI and when entered in the study. Maximum daily dose of 24 mg/day of dexamethasone/decadron or equivalent

Abbreviated Exclusion Criteria:

  • Patients who are sexually active and not willing to use barrier methods of contraception; women who are breastfeeding
  • Patients with unstable or serious concurrent medical or psychiatric conditions that would interfere with study treatment or follow-up
  • Patients with more than one discrete enhancing lesion on MRI, or radiographic evidence of satellite lesions or leptomeningeal disease not obviously contiguous by FLAIR imaging
  • Patients who may require further neurosurgery within 4 weeks after REOLYSIN® treatment
  • Patients with a prior history of encephalitis, multiple sclerosis or other significant chronic CNS disease
  • Patients who have evidence of a current CNS infection, meningeal gliomatosis or gliomatosis cerebri
  • Patients with tumor that to be treated would require needle or catheter passage through a ventricle, the posterior fossa or basal ganglia; or patients with tumors invading the ventricle
  • Patients who have previously participated in experimental viral therapy protocols
  • Patients who have had prior intratumoral gene therapy or other intratumoral therapies
  • Patients who have had Gliadel wafer therapy less than 6 months prior to enrollment
  • Patients who have a history of bleeding disorders including congenital or acquired coagulopathies
  • Patients who have a known history of hepatitis or tuberculosis
  • Patients who have a known history of hereditary or acquired immunodeficiency including HIV infection
  • Patients who have impaired non-neurological organ function (>Grade 1)
  • Patients who have used systemic antiviral (or potentially antiviral) therapies within 28 days of enrollment
  • Patients who have had brachytherapy or radiosurgery to the brain at any time
  • Patients with previous or concurrent malignancies at other sites (except surgically-cured carcinoma in situ of the cervix and non-melanoma skin cancer)
  • Prior or current medical history indicating that a patient may be significantly immunosuppressed

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
determine the maximum tolerated dose
Time Frame: in the first 28 days following REOLYSIN® administration
in the first 28 days following REOLYSIN® administration
and response rate of treated tumors
Time Frame: evaluated monthly for 6 months following REOLYSIN® administration
evaluated monthly for 6 months following REOLYSIN® administration
determine the dose limiting toxicity
Time Frame: in the first 28 days following REOLYSIN® administration
in the first 28 days following REOLYSIN® administration

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Determine the patient survival
Time Frame: patients are in follow up for up to six months
patients are in follow up for up to six months
functional status using the Karnofsky Performance Status scale and Clinical Neurological Assessment
Time Frame: evaluated monthly for up to 6 months
evaluated monthly for up to 6 months
time to progression for the treated tumor
Time Frame: evaluated monthly for up to 6 months
evaluated monthly for up to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Oncolytics Biotech

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: James M Markert, MD, University of Alabama at Birmingham

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 10, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 10, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 12, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 2, 2014

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 30, 2014

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • REO 007

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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