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G207 Followed by Radiation Therapy in Malignant Glioma

Primary Purpose

Malignant Glioma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
G207
Sponsored by
MediGene
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Glioma focused on measuring Malignant glioma, Glioblastoma multiforme, GBM, Gliosarcoma, Anaplastic astrocytoma, Brain cancer, Brain tumor, Glioma, recurrent/progressive malignant glioma

Eligibility Criteria

19 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Pathologically proven residual/recurrent glioblastoma multiforme, gliosarcoma or anaplastic astrocytoma which is progressive despite radiotherapy or chemotherapy Failed external beam radiotherapy > 5,000 CGy at least 4 weeks prior to enrollment Residual/recurrent lesion must be ≥ 1.0 cm and (for Stage 2 only) ≤ 4 cm in diameter as determined by magnetic resonance imaging (MRI) Normal hematological, renal and liver function Absolute neutrophil count > 1500/mm3 Platelets > 100,000/mm3 Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.3 x control Creatinine < 1.7 mg/dl Total bilirubin < 1.5 mg/dl Transaminases < 4 times above the upper limits of the institutional norm Karnofsky Performance Status score ≥ 70 Age > 19 years-old Capable of giving informed consent Must be willing to practice an effective barrier method of birth control for 2 months post G207 inoculation, whether male or female Females of childbearing potential: negative pregnancy test within 24 hours prior to G207 administration Exclusion Criteria: Surgical resection within 4 weeks of enrolment Acute infection, granulocytopenia or medical condition precluding surgery Pregnant or lactating females History of encephalitis, multiple sclerosis, or other central nervous system (CNS) infection Tumor involvement which would require ventricular, brainstem, basal ganglia, or posterior fossa inoculation or would require access through a ventricle in order to deliver treatment or tumor involving both hemispheres or with subependymal/cerebral spinal fluid (CSF) dissemination Tumor position that could, in the Investigator's opinion, pose the risk of penetration of the cerebral ventricular system during inoculation with the study drug (Note: If penetration of the ventricular system is suspected or confirmed, G207 administration must be aborted.) Tumor locations that would expose the patient to unacceptable risk with radiation therapy Prior participant in experimental viral therapy (e.g., adenovirus, retrovirus or herpesvirus protocol) Prior participant in chemotherapy, cytotoxic therapy, immunotherapy or gene therapy protocol within 6 weeks of enrolment Required steroid increase within 2 weeks prior to injection HIV seropositive Concurrent therapy with any drug active against herpes simplex virus (HSV) (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscavir, cidofovir) Active oral or genital herpes lesion Any contraindication for undergoing MRI such as pacemakers, infusion pumps, ferromagnetic aneurysm clips, metal prostheses, etc. Radiation treatment volume of greater than 4 cm maximum diameter (Stage 2 only)

Sites / Locations

  • University of Alabama at Birmingham

Outcomes

Primary Outcome Measures

Adverse events

Secondary Outcome Measures

Radiographic response
Performance scale
Overall survival
Immune response
Presence of G207 in blood and saliva

Full Information

First Posted
September 8, 2005
Last Updated
December 12, 2008
Sponsor
MediGene
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00157703
Brief Title
G207 Followed by Radiation Therapy in Malignant Glioma
Official Title
A Staged Phase 1 Study of the Treatment of Malignant Glioma With G207, a Genetically Engineered HSV-1, Followed by Radiation Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
December 2008
Overall Recruitment Status
Completed
Study Start Date
May 2005 (undefined)
Primary Completion Date
October 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
MediGene
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is an open-label, single site study to evaluate the safety and tolerability of intratumoral administration of G207 followed by treatment with radiation therapy in patients with recurrent/progressive malignant glioma. This study is a two stage phase 1 study, in which a de-escalating dosing scheme will be used, i.e. the first patients will receive the higher dose and if excessive toxicity occurs, the dose will be reduced for the following patients. The purpose of the dose de-escalation phase is to find the best safe dose of G207. In the first stage of the study, treatment with G207 will be followed by focal radiation therapy on the following day, and in the second stage treatment with G207 will be followed by gamma knife surgery also on the following day. All patients will return to the clinic 28 days and 3, 6, 9 and 12 months after G207 administration at which time clinical assessments will be performed, and will be followed for safety and survival at clinic visits or by telephone every 3 months for up to 2 additional years and annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Glioma
Keywords
Malignant glioma, Glioblastoma multiforme, GBM, Gliosarcoma, Anaplastic astrocytoma, Brain cancer, Brain tumor, Glioma, recurrent/progressive malignant glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
G207
Intervention Description
1 x 10E9 plaque forming units, administered by stereotactic injections into the tumor (single administration)
Primary Outcome Measure Information:
Title
Adverse events
Time Frame
from 1st dose to end of study visit
Secondary Outcome Measure Information:
Title
Radiographic response
Time Frame
Withdrawal or death of last patient
Title
Performance scale
Time Frame
Last patient out
Title
Overall survival
Time Frame
Withdrawal or death of last patient
Title
Immune response
Time Frame
Last patient out
Title
Presence of G207 in blood and saliva
Time Frame
Last patient out

10. Eligibility

Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically proven residual/recurrent glioblastoma multiforme, gliosarcoma or anaplastic astrocytoma which is progressive despite radiotherapy or chemotherapy Failed external beam radiotherapy > 5,000 CGy at least 4 weeks prior to enrollment Residual/recurrent lesion must be ≥ 1.0 cm and (for Stage 2 only) ≤ 4 cm in diameter as determined by magnetic resonance imaging (MRI) Normal hematological, renal and liver function Absolute neutrophil count > 1500/mm3 Platelets > 100,000/mm3 Prothrombin time (PT) or partial thromboplastin time (PTT) < 1.3 x control Creatinine < 1.7 mg/dl Total bilirubin < 1.5 mg/dl Transaminases < 4 times above the upper limits of the institutional norm Karnofsky Performance Status score ≥ 70 Age > 19 years-old Capable of giving informed consent Must be willing to practice an effective barrier method of birth control for 2 months post G207 inoculation, whether male or female Females of childbearing potential: negative pregnancy test within 24 hours prior to G207 administration Exclusion Criteria: Surgical resection within 4 weeks of enrolment Acute infection, granulocytopenia or medical condition precluding surgery Pregnant or lactating females History of encephalitis, multiple sclerosis, or other central nervous system (CNS) infection Tumor involvement which would require ventricular, brainstem, basal ganglia, or posterior fossa inoculation or would require access through a ventricle in order to deliver treatment or tumor involving both hemispheres or with subependymal/cerebral spinal fluid (CSF) dissemination Tumor position that could, in the Investigator's opinion, pose the risk of penetration of the cerebral ventricular system during inoculation with the study drug (Note: If penetration of the ventricular system is suspected or confirmed, G207 administration must be aborted.) Tumor locations that would expose the patient to unacceptable risk with radiation therapy Prior participant in experimental viral therapy (e.g., adenovirus, retrovirus or herpesvirus protocol) Prior participant in chemotherapy, cytotoxic therapy, immunotherapy or gene therapy protocol within 6 weeks of enrolment Required steroid increase within 2 weeks prior to injection HIV seropositive Concurrent therapy with any drug active against herpes simplex virus (HSV) (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscavir, cidofovir) Active oral or genital herpes lesion Any contraindication for undergoing MRI such as pacemakers, infusion pumps, ferromagnetic aneurysm clips, metal prostheses, etc. Radiation treatment volume of greater than 4 cm maximum diameter (Stage 2 only)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Axel Mescheder, M.D.
Organizational Affiliation
Medigene AG
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294-3410
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24572293
Citation
Markert JM, Razdan SN, Kuo HC, Cantor A, Knoll A, Karrasch M, Nabors LB, Markiewicz M, Agee BS, Coleman JM, Lakeman AD, Palmer CA, Parker JN, Whitley RJ, Weichselbaum RR, Fiveash JB, Gillespie GY. A phase 1 trial of oncolytic HSV-1, G207, given in combination with radiation for recurrent GBM demonstrates safety and radiographic responses. Mol Ther. 2014 May;22(5):1048-55. doi: 10.1038/mt.2014.22. Epub 2014 Feb 27.
Results Reference
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G207 Followed by Radiation Therapy in Malignant Glioma

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