G207 Followed by Radiation Therapy in Malignant Glioma

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
MediGene
ClinicalTrials.gov Identifier:
NCT00157703
First received: September 8, 2005
Last updated: December 12, 2008
Last verified: December 2008
  Purpose

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 Intervention Phase
Malignant Glioma
Drug: G207
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by MediGene:

Primary Outcome Measures:
  • Adverse events [ Time Frame: from 1st dose to end of study visit ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Radiographic response [ Time Frame: Withdrawal or death of last patient ] [ Designated as safety issue: No ]
  • Performance scale [ Time Frame: Last patient out ] [ Designated as safety issue: Yes ]
  • Overall survival [ Time Frame: Withdrawal or death of last patient ] [ Designated as safety issue: No ]
  • Immune response [ Time Frame: Last patient out ] [ Designated as safety issue: No ]
  • Presence of G207 in blood and saliva [ Time Frame: Last patient out ] [ Designated as safety issue: Yes ]

Enrollment: 9
Study Start Date: May 2005
Study Completion Date: December 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: G207
    1 x 10E9 plaque forming units, administered by stereotactic injections into the tumor (single administration)
  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00157703

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-3410
Sponsors and Collaborators
MediGene
Investigators
Study Director: Axel Mescheder, M.D. Medigene AG
  More Information

No publications provided by MediGene

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alice Chen, MediGene
ClinicalTrials.gov Identifier: NCT00157703     History of Changes
Other Study ID Numbers: CT2001
Study First Received: September 8, 2005
Last Updated: December 12, 2008
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 21, 2014