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

NCT00528684 | Completed Phase 1 DMC

• 1 other identifier: REO 007
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 3

Brief Summary

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.)

Conditions

Malignant Glioma

Keywords

Oncolytics Biotech; cancer alternative therapies; malignant glioma; glioblastoma multiforme; oncolytic virus; reovirus; REOLYSIN

Outcome Measures

Primary Outcomes (3)

• determine the maximum tolerated dose

  in the first 28 days following REOLYSIN® administration

• and response rate of treated tumors

  evaluated monthly for 6 months following REOLYSIN® administration

• determine the dose limiting toxicity

  in the first 28 days following REOLYSIN® administration

Secondary Outcomes (3)

• Determine the patient survival

  patients are in follow up for up to six months

• functional status using the Karnofsky Performance Status scale and Clinical Neurological Assessment

  evaluated monthly for up to 6 months

• time to progression for the treated tumor

  evaluated monthly for up to 6 months

Interventions

REOLYSIN® BIOLOGICAL

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.

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oncolytics Biotech: lead

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

The Ohio State University Medical Center and Arthur G. James Cancer Hospital and Richard J. Solove Research Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

reolysin

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

Study Officials

• James M Markert, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2007
• First Posted: September 12, 2007
• Study Start: July 1, 2006
• Primary Completion: April 1, 2010
• Study Completion: June 1, 2010
• Last Updated: October 2, 2014

Record last verified: 2011-09

Locations

US (3)