Safety and Effectiveness Study of G207, a Tumor-Killing Virus, in Patients With Recurrent Brain Cancer

June 23, 2005 updated by: MediGene

An Open-Label Phase Ib/II Study of the Safety, Tolerability and Efficacy of G207, a Genetically Engineered Herpes Simplex Type-1 Virus, Administered Intracerebrally to Patients With Recurrent Malignant Glioma

This clinical trial will study the safety and effectiveness of an engineered herpes virus, G207, administered directly into the brain of patients with recurrent brain cancer. G207 has been modified from the herpes virus that causes cold sores (called herpes simplex virus type 1 or HSV-1). G207 has been designed so that it should kill tumor cells, but not harm normal brain cells. G207 has been shown to be safe in animal testing completed to date and in previous studies in patients with brain tumors.

This is a phase Ib/II study. In the phase Ib portion of the study, patients will receive G207 at a dose that is higher than tested in previous human studies. Patients will initially receive 15% of the assigned dose injected directly into the brain tumor. Approximately two days later, as much of the tumor as possible will be surgically removed, and more G207 will be injected into the brain tumor bed. Patients will be monitored, and medical tests will be done at specific study timepoints.

The phase II portion will begin only if there are no safety concerns in the phase Ib portion. The goals of the phase II portion of the study are to determine the safety of G207 and to study patient survival at six months after G207 dosing. In the phase II portion of the study, patients will receive a single dose of G207 at the highest dose determined to be safe in the phase Ib portion of the study. The tumor will be removed, and G207 will be injected into any remaining tumor tissue in the brain tumor bed. Patients will be closely monitored, medical tests will be performed at specific study visits, and survival will be evaluated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Protocol NG1-003 is an open-label, phase Ib/II study of the safety and efficacy of G207, a genetically engineered herpes simplex type-1 virus. Up to 21 patients will be enrolled in the phase Ib portion and will receive doses of G207 that are higher than tested in the previous trials. The highest G207 dose tested in a previous phase I trial (NG1-001) was 3E9 plaque forming units (pfu). G207 was generally well tolerated and safe in NG1-001, and there was no dose-limiting toxicity. Patients' deaths were due to progressive cancer disease except for one (due to radiation necrosis), and two patients remain alive today.

Patients in the phase Ib portion of NG1-003 will receive G207 in divided doses. Initially, 15% of the assigned dose will be injected into the tumor. Two days later, the tumor will be removed, and the assigned dose of G207 will be injected into the tumor bed at the time of resection. The assigned doses are as follows: 1E9, 3E9, and 1E10 pfu. Patient status will be followed by MRI, Karnofsky performance, neurologic examination and the presence of G207 virus in the body, in addition to other medical tests done at specific study visits.

The phase II portion of protocol NG1-003 is a two-stage study. The phase II portion will begin only if there are no safety concerns in the phase Ib portion. The goals are to determine the safety of G207 and survival at six months. Enrollment of up to 14 patients is planned for stage one. Additional patients will be enrolled (up to 30 additional patients and 44 overall) in stage II if at least 6 of the 14 patients in stage 1 survive 6 months or longer. Participants in phase II will receive a single dose of G207 at the highest dose determined to be safe from phase Ib. G207 will be injected into the tumor bed at the time of resection. Again, patient status will be followed as previously described and survival will be evaluated.

Study Type

Interventional

Enrollment

65

Phase

  • Phase 2
  • Phase 1

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

Ages Eligible for Study

17 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Main Inclusion Criteria:

  • Age 19 years and older
  • Phase Ib: Histologically confirmed recurrent glioblastoma multiforme or gliosarcoma (recurrent anaplastic astrocytoma also included in phase Ib) that is progressive despite previous radio- or chemotherapy
  • Phase II: Histologically confirmed recurrent glioblastoma multiforme or gliosarcoma that is progressive despite previous radio- or chemotherapy
  • Enhancing brain tumor measures at least 1.0 cm in diameter and evaluable by MRI within 14 days of G207 administration (and proposed area of study drug inoculation appears to be resectable en bloc--for phase Ib only)
  • Steroid regimen stable for at least 1 week prior to G207 inoculation
  • Karnofsky Performance Status 70% or greater
  • Failed external beam radiotherapy of at least 5000 cGy 4 weeks or longer prior to G207 administration
  • Candidate for brain tumor resection
  • Females: negative urine pregnancy test within 24 hours prior to G207 administration
  • Willing to use effective barrier birth control
  • Able to give informed consent

Main Exclusion Criteria:

  • Multiple (more than one) intracranial malignant glioma lesions
  • Documented extracranial metastases
  • Laboratory test values (CBC, platelets, clinical chemistry, liver and renal function tests) outside protocol specified limits
  • Chemotherapy, cytotoxic or immunotherapy within 6 weeks of G207 administration
  • Any contraindication for undergoing MRI such as pacemakers, infusion pumps, aneurysm clips, metal prosthesis, former welders etc.
  • Surgical resection within 4 weeks of G207 administration
  • Pregnant or nursing females
  • History of any of the following: HIV seropositive (historical or known); other investigational agents or vaccinations within 30 days; encephalitis, multiple sclerosis or other CNS infection; prior gene transfer therapy or prior therapy with a cytolytic virus of any type
  • Any of the following concurrent conditions: evidence of active herpes infection; requires antiviral therapy for HSV at baseline; previous history or current diagnosis of other cancer except curative cervical cancer in situ or basal or squamous cell carcinoma of the skin; active uncontrolled infection, granulocytopenia, any unstable or severe medical condition that precludes surgery; alcohol or other substance abuse

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: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Collaborators and Investigators

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

Sponsor

MediGene

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

December 1, 2001

Study Completion

October 1, 2003

Study Registration Dates

First Submitted

December 17, 2001

First Submitted That Met QC Criteria

December 17, 2001

First Posted (Estimate)

December 18, 2001

Study Record Updates

Last Update Posted (Estimate)

June 24, 2005

Last Update Submitted That Met QC Criteria

June 23, 2005

Last Verified

December 1, 2001

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NG1-003

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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