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An Open-Label Phase Ib/II Study of the Safety, Tolerability and Efficacy of G207, a Genetically Engineered Herpes Simplex Type-1 Virus, Administered Intracerebrally to Patients With Recurrent Malignant Glioma


Phase 1/Phase 2
19 Years
N/A
Not Enrolling
Both
Glioma, Astrocytoma, Glioblastoma

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Trial Information

An Open-Label Phase Ib/II Study of the Safety, Tolerability and Efficacy of G207, a Genetically Engineered Herpes Simplex Type-1 Virus, Administered Intracerebrally to Patients With Recurrent Malignant Glioma


Protocol NG1-003 is an open-label, phase Ib/II study of the safety and efficacy of G207, a
genetically engineered herpes simplex type-1 virus. Up to 21 patients will be enrolled in
the phase Ib portion and will receive doses of G207 that are higher than tested in the
previous trials. The highest G207 dose tested in a previous phase I trial (NG1-001) was 3E9
plaque forming units (pfu). G207 was generally well tolerated and safe in NG1-001, and
there was no dose-limiting toxicity. Patients' deaths were due to progressive cancer
disease except for one (due to radiation necrosis), and two patients remain alive today.

Patients in the phase Ib portion of NG1-003 will receive G207 in divided doses. Initially,
15% of the assigned dose will be injected into the tumor. Two days later, the tumor will be
removed, and the assigned dose of G207 will be injected into the tumor bed at the time of
resection. The assigned doses are as follows: 1E9, 3E9, and 1E10 pfu. Patient status will
be followed by MRI, Karnofsky performance, neurologic examination and the presence of G207
virus in the body, in addition to other medical tests done at specific study visits.

The phase II portion of protocol NG1-003 is a two-stage study. The phase II portion will
begin only if there are no safety concerns in the phase Ib portion. The goals are to
determine the safety of G207 and survival at six months. Enrollment of up to 14 patients is
planned for stage one. Additional patients will be enrolled (up to 30 additional patients
and 44 overall) in stage II if at least 6 of the 14 patients in stage 1 survive 6 months or
longer. Participants in phase II will receive a single dose of G207 at the highest dose
determined to be safe from phase Ib. G207 will be injected into the tumor bed at the time
of resection. Again, patient status will be followed as previously described and survival
will be evaluated.


Main

Inclusion Criteria:



- Age 19 years and older

- Phase Ib: Histologically confirmed recurrent glioblastoma multiforme or gliosarcoma
(recurrent anaplastic astrocytoma also included in phase Ib) that is progressive
despite previous radio- or chemotherapy

- Phase II: Histologically confirmed recurrent glioblastoma multiforme or gliosarcoma
that is progressive despite previous radio- or chemotherapy

- Enhancing brain tumor measures at least 1.0 cm in diameter and evaluable by MRI
within 14 days of G207 administration (and proposed area of study drug inoculation
appears to be resectable en bloc--for phase Ib only)

- Steroid regimen stable for at least 1 week prior to G207 inoculation

- Karnofsky Performance Status 70% or greater

- Failed external beam radiotherapy of at least 5000 cGy 4 weeks or longer prior to
G207 administration

- Candidate for brain tumor resection

- Females: negative urine pregnancy test within 24 hours prior to G207 administration

- Willing to use effective barrier birth control

- Able to give informed consent

Main Exclusion Criteria:

- Multiple (more than one) intracranial malignant glioma lesions

- Documented extracranial metastases

- Laboratory test values (CBC, platelets, clinical chemistry, liver and renal function
tests) outside protocol specified limits

- Chemotherapy, cytotoxic or immunotherapy within 6 weeks of G207 administration

- Any contraindication for undergoing MRI such as pacemakers, infusion pumps, aneurysm
clips, metal prosthesis, former welders etc.

- Surgical resection within 4 weeks of G207 administration

- Pregnant or nursing females

- History of any of the following: HIV seropositive (historical or known); other
investigational agents or vaccinations within 30 days; encephalitis, multiple
sclerosis or other CNS infection; prior gene transfer therapy or prior therapy with a
cytolytic virus of any type

- Any of the following concurrent conditions: evidence of active herpes infection;
requires antiviral therapy for HSV at baseline; previous history or current diagnosis
of other cancer except curative cervical cancer in situ or basal or squamous cell
carcinoma of the skin; active uncontrolled infection, granulocytopenia, any unstable
or severe medical condition that precludes surgery; alcohol or other substance abuse

Type of Study:

Interventional

Study Design:

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

Authority:

United States: Food and Drug Administration

Study ID:

NG1-003

NCT ID:

NCT00028158

Start Date:

December 2001

Completion Date:

October 2003

Related Keywords:

  • Glioma
  • Astrocytoma
  • Glioblastoma
  • Antineoplastic agents
  • Herpes virus
  • Brain tumor
  • Oncolytic virs
  • Astrocytoma
  • Glioblastoma
  • Glioma

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