Clinical trial NCT00157703: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignant Glioma
Keywords: Malignant glioma
Glioblastoma multiforme
GBM
Gliosarcoma
Anaplastic astrocytoma
Brain cancer
Brain tumor
Glioma
recurrent/progressive malignant glioma
Lead sponsor: MediGene
Sponsor class: INDUSTRY
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-09-12
Enrollment: 9
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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)

Primary outcomes:
measure: Adverse events
timeFrame: from 1st dose to end of study visit
Secondary outcomes:
measure: Radiographic response
timeFrame: Withdrawal or death of last patient
measure: Performance scale
timeFrame: Last patient out
measure: Overall survival
timeFrame: Withdrawal or death of last patient
measure: Immune response
timeFrame: Last patient out
measure: Presence of G207 in blood and saliva
timeFrame: Last patient out
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: Medigene AG
name: Axel Mescheder, M.D.
role: STUDY_DIRECTOR
References:
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.