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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

Phase 1
18 Years
Not Enrolling
Malignant Glioma

Thank you

Trial Information

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

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.


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®

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

determine the maximum tolerated dose

Outcome Time Frame:

in the first 28 days following REOLYSIN® administration

Safety Issue:


Principal Investigator

James M Markert, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Alabama at Birmingham


United States: Food and Drug Administration

Study ID:

REO 007



Start Date:

July 2006

Completion Date:

June 2010

Related Keywords:

  • Malignant Glioma
  • Oncolytics Biotech
  • cancer alternative therapies
  • malignant glioma
  • glioblastoma multiforme
  • oncolytic virus
  • reovirus
  • Glioma



Cedars-Sinai Medical Center Los Angeles, California  90048
University of Alabama at Birmingham Birmingham, Alabama  35294-3300
The Ohio State University Medical Center and Arthur G. James Cancer Hospital and Richard J. Solove Research Center Columbus, Ohio  43210