G207 Followed by Radiation Therapy in Malignant Glioma

A Staged Phase 1 Study of the Treatment of Malignant Glioma With G207, a Genetically Engineered HSV-1, Followed by Radiation Therapy

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.

Study Overview

• Status: Completed
• Conditions: Malignant Glioma
• Intervention / Treatment: Drug: G207

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events	from 1st dose to end of study visit

Secondary Outcome Measures

Outcome Measure	Time Frame
Radiographic response	Withdrawal or death of last patient
Performance scale	Last patient out
Overall survival	Withdrawal or death of last patient
Immune response	Last patient out
Presence of G207 in blood and saliva	Last patient out

Collaborators and Investigators

• Sponsor: MediGene
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Director: Axel Mescheder, M.D., Medigene AG

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (ACTUAL): October 1, 2008
• Study Completion (ACTUAL): December 1, 2008

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 8, 2005
• First Posted (ESTIMATE): September 12, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): December 16, 2008
• Last Update Submitted That Met QC Criteria: December 12, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: Glioma; GBM; Brain tumor; Anaplastic astrocytoma; Gliosarcoma; Glioblastoma multiforme; Malignant glioma; Brain cancer; recurrent/progressive malignant glioma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioma
• Other Study ID Numbers: CT2001