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Safety and Efficacy Study of REOLYSIN® in the Treatment of Recurrent Malignant Gliomas
This study is currently recruiting participants.
Verified by Oncolytics Biotech, August 2009
First Received: September 10, 2007   Last Updated: August 20, 2009   History of Changes
Sponsor: Oncolytics Biotech
Information provided by: Oncolytics Biotech
ClinicalTrials.gov Identifier: NCT00528684
  Purpose

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.)


Condition Intervention Phase
Malignant Glioma
Biological: REOLYSIN®
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Oncolytics Biotech:

Primary Outcome Measures:
  • determine the maximum tolerated dose [ Time Frame: in the first 28 days following REOLYSIN® administration ] [ Designated as safety issue: Yes ]
  • and response rate of treated tumors [ Time Frame: evaluated monthly for 6 months following REOLYSIN® administration ] [ Designated as safety issue: No ]
  • determine the dose limiting toxicity [ Time Frame: in the first 28 days following REOLYSIN® administration ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine the patient survival [ Time Frame: patients are in follow up for up to six months ] [ Designated as safety issue: No ]
  • functional status using the Karnofsky Performance Status scale and Clinical Neurological Assessment [ Time Frame: evaluated monthly for up to 6 months ] [ Designated as safety issue: No ]
  • time to progression for the treated tumor [ Time Frame: evaluated monthly for up to 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: July 2006
Estimated Study Completion Date: March 2010
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: REOLYSIN®
    REOLYSIN® is administered as a single intratumoral infusion over 72 hours. Dose levels in Phase 1 will be 1x10E8, 3x10E8, 1x10E9, 3x10E9, 1x10E10 TCID50. The dose level for Phase 2 will be the top dose reached in Phase 1.
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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00528684

Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Beth D. Casey, RN     205-934-1848     bdean@uab.edu    
Principal Investigator: James M Markert, MD            
United States, California
Cedars-Sinai Medical Center Recruiting
Los Angeles, California, United States, 90048
Contact: John S Yu, MD     310-423-7900     John.Yu@cshs.org    
Principal Investigator: John S Yu, MD            
United States, Ohio
The Ohio State University Medical Center and Arthur G. James Cancer Hospital and Richard J. Solove Research Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Susan D Bell, RN     614-293-3143     Susan.Bell@osumc.edu    
Principal Investigator: E. Antonio Chiocca, MD, PhD            
Sponsors and Collaborators
Oncolytics Biotech
Investigators
Principal Investigator: James M Markert, MD University of Alabama at Birmingham
  More Information

Additional Information:
No publications provided

Responsible Party: Oncolytics Biotech Inc. ( Karl Mettinger, MD, PhD/Chief Medical Officer )
Study ID Numbers: REO 007
Study First Received: September 10, 2007
Last Updated: August 20, 2009
ClinicalTrials.gov Identifier: NCT00528684     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by Oncolytics Biotech:
Oncolytics Biotech
cancer alternative therapies
malignant glioma
glioblastoma multiforme
oncolytic virus
reovirus
REOLYSIN

Additional relevant MeSH terms:
Neuroectodermal Tumors
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Glioma
Neoplasms, Neuroepithelial
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 25, 2009