G207 Followed by Radiation Therapy in Malignant Glioma

Malignant Glioma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00157703
• Other study ID #: CT2001
• Status: Completed
• Phase: Phase 1
• First received: September 8, 2005
• Last updated: December 12, 2008
• Start date: May 2005
• Est. completion date: December 2008

Study information

• Verified date: December 2008
• Source: MediGene
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: December 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioma
• Malignant Glioma

Intervention

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

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (2)

Lead Sponsor	Collaborator
MediGene	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events		from 1st dose to end of study visit	Yes
Secondary	Radiographic response		Withdrawal or death of last patient	No
Secondary	Performance scale		Last patient out	Yes
Secondary	Overall survival		Withdrawal or death of last patient	No
Secondary	Immune response		Last patient out	No
Secondary	Presence of G207 in blood and saliva		Last patient out	Yes