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IL-12-Expressing HSV-1 in Treating Patients with Recurrent or Progressive Glioblastoma, Anaplastic Astrocytoma, or Gliosarcoma

Trial Status: Active

This phase I trial studies the side effects and best dose of interleukin (IL)-12-expressing human herpesvirus 1 (HSV-1) in treating patients with glioblastoma, anaplastic astrocytoma, or gliosarcoma that has come back or is growing, spreading, or getting worse. A virus, called IL-12-expressing HSV-1, which has been changed in a certain way, may be able to kill tumor cells without damaging normal cells.

Inclusion Criteria

  • Patients must have histologically or cytologically confirmed glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma
  • Patients must have failed external beam radiotherapy >= 5,000 cGy to the brain, and if eligible and tolerated, undergone appropriate treatment with temozolomide chemotherapy; all radiation and additional chemotherapies must have been completed at least 4 weeks prior to enrollment; prior therapy with nitrosoureas must have been completed at least 6 weeks prior to enrollment
  • Karnofsky performance status (KPS) >= 70%
  • Life expectancy of greater than 4 weeks
  • Leukocytes >= 3,000/ul
  • Absolute neutrophil count >= 1,500/ul
  • Platelets >= 100,000/ul
  • Total bilirubin within normal institutional limits
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
  • Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Residual lesion must be >= 1.0 cm in diameter as determined by magnetic resonance imaging (MRI)
  • Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the first six months after receiving M032; a barrier method of birth control must be employed and for six (6) months following the administration of the study drug; should a woman become pregnant while participating in this study, she should inform her treating physician immediately; for two weeks after receiving M032, subjects should avoid intimate contact with pregnant women, infants and young children and individuals with decreased immunity (ability to fight infection); subjects should also refrain from donating blood during the trial
  • Ability to understand and the willingness to sign a written informed consent document
  • Females of childbearing potential must not be pregnant; this will be confirmed by a negative serum pregnancy test within 14 days prior to starting study treatment
  • Steroid use is allowed as long as dose has not increased within 2 weeks of scheduled M032 administration; whenever possible, the patient should be on a steroid dose that is equivalent to a dexamethasone dose of =< 2 mg daily at the time of treatment

Exclusion Criteria

  • Patients who have had chemotherapy, cytotoxic therapy, immunotherapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas), surgical resection within 4 weeks prior to entering the study, or have received experimental viral therapy or gene therapy at any time (e.g., adenovirus, retrovirus or herpes virus protocol); however, this does not preclude re-treatment with M032 at a later date
  • Patients who have not recovered from adverse events due to therapeutic interventions administered more than 4 weeks earlier
  • Patients may not be receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar biologic composition to M032 or to IL-12
  • 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
  • Prior history of encephalitis, multiple sclerosis, or other central nervous system (CNS) infection
  • Required steroid increase within 2 weeks of scheduled M032 administration; when possible, the patient should be on a dexamethasone equivalent dose of =< 2 mg daily at the time of treatment
  • Active herpes lesion
  • Concurrent therapy with any drug active against simplexvirus (HSV) (acyclovir, valacyclovir, penciclovir, famcyclovir, gancyclovir, foscarnet, cidofovir)
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other medical condition that precludes surgery; also, psychiatric illness/social situations that would limit compliance with study requirements
  • Excluded patient groups: * Pregnant women are excluded from this study; breastfeeding women will not be included in the study * Human immunodeficiency virus (HIV)-seropositive patients are excluded from this study
  • Patients with known history of allergic reaction to intravenous (IV) contrast material that is not amenable to pre-treatment by University of Alabama at Birmingham (UAB) protocol
  • Patients with pacemakers, ferro-magnetic aneurysm clips, metal infusion pumps, metal or shrapnel fragments or certain types of stents
  • Receipt of Gliadel therapy
  • Receipt of bevacizumab (Avastin) therapy within 4 weeks of scheduled M032 administration; (receipt of bevacizumab [Avastin] greater than 4 weeks of scheduled M032 administration does not exclude patient)

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: ACTIVE
Contact: Kristen Riley
Phone: 205-966-2461

PRIMARY OBJECTIVES:

I. To determine, in patients who would not be eligible for resection of recurrent glioma, the safety and tolerability of stereotactic intracerebral injections of escalating doses of IL-12-expressing HSV-1 (M032 virus [NSC 733972]), and to determine the maximally tolerated dose (MTD) of M032.

SECONDARY OBJECTIVES:

I. To obtain preliminary information about the potential benefit of M032 in the treatment of patients with recurrent malignant gliomas (progression-free survival, overall survival).

TERTIARY OBJECTIVES:

I. To delineate the local and systemic immune response to M032 administration.

II. To characterize the in situ biologic activity of M032 after intratumoral inoculation, where possible.

OUTLINE: This is a dose-escalation study.

Patients receive IL-12-expressing HSV-1 intratumorally over 6 hours on day 1 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at day 10 and months 1, 2, 3, 4, 5, 6, 9, and 12.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
University of Alabama at Birmingham Cancer Center

Principal Investigator
Kristen Riley

  • Primary ID UAB1317
  • Secondary IDs NCI-2016-01806
  • Clinicaltrials.gov ID NCT02062827