G207 Followed by Radiation Therapy in Malignant Glioma

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Malignant Glioma	Drug: G207	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	9 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	May 2005
Actual Primary Completion Date :	October 2008
Actual Study Completion Date :	December 2008

Arms and Interventions

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Intervention Details:

Drug: G207
1 x 10E9 plaque forming units, administered by stereotactic injections into the tumor (single administration)

Outcome Measures

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Primary Outcome Measures :

1. Adverse events [ Time Frame: from 1st dose to end of study visit ]

Secondary Outcome Measures :

1. Radiographic response [ Time Frame: Withdrawal or death of last patient ]
2. Performance scale [ Time Frame: Last patient out ]
3. Overall survival [ Time Frame: Withdrawal or death of last patient ]
4. Immune response [ Time Frame: Last patient out ]
5. Presence of G207 in blood and saliva [ Time Frame: Last patient out ]

Eligibility Criteria

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Ages Eligible for Study:	19 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

1. Pathologically proven residual/recurrent glioblastoma multiforme, gliosarcoma or anaplastic astrocytoma which is progressive despite radiotherapy or chemotherapy
2. Failed external beam radiotherapy > 5,000 CGy at least 4 weeks prior to enrollment
3. Residual/recurrent lesion must be ≥ 1.0 cm and (for Stage 2 only) ≤ 4 cm in diameter as determined by magnetic resonance imaging (MRI)

4. 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
5. Karnofsky Performance Status score ≥ 70
6. Age > 19 years-old
7. Capable of giving informed consent
8. Must be willing to practice an effective barrier method of birth control for 2 months post G207 inoculation, whether male or female
9. Females of childbearing potential: negative pregnancy test within 24 hours prior to G207 administration

Exclusion Criteria:

1. Surgical resection within 4 weeks of enrolment
2. Acute infection, granulocytopenia or medical condition precluding surgery
3. Pregnant or lactating females
4. History of encephalitis, multiple sclerosis, or other central nervous system (CNS) infection
5. 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
6. 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.)
7. Tumor locations that would expose the patient to unacceptable risk with radiation therapy
8. Prior participant in experimental viral therapy (e.g., adenovirus, retrovirus or herpesvirus protocol)
9. Prior participant in chemotherapy, cytotoxic therapy, immunotherapy or gene therapy protocol within 6 weeks of enrolment
10. Required steroid increase within 2 weeks prior to injection
11. HIV seropositive
12. Concurrent therapy with any drug active against herpes simplex virus (HSV) (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscavir, cidofovir)
13. Active oral or genital herpes lesion
14. Any contraindication for undergoing MRI such as pacemakers, infusion pumps, ferromagnetic aneurysm clips, metal prostheses, etc.
15. Radiation treatment volume of greater than 4 cm maximum diameter (Stage 2 only)

Contacts and Locations

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Locations

United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-3410

Sponsors and Collaborators

MediGene

National Cancer Institute (NCI)

Investigators

Study Director:	Axel Mescheder, M.D.	Medigene AG

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Alice Chen, MediGene
ClinicalTrials.gov Identifier:	NCT00157703 History of Changes
Other Study ID Numbers:	CT2001
First Posted:	September 12, 2005
Last Update Posted:	December 16, 2008
Last Verified:	December 2008

Keywords provided by MediGene:

Malignant glioma; Glioblastoma multiforme; GBM; Gliosarcoma; Anaplastic astrocytoma	Brain cancer; Brain tumor; Glioma; recurrent/progressive malignant glioma

Additional relevant MeSH terms:

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal	Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue