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About
This phase I trial studies the side effects and the safety of injecting HSV1716 (a new experimental therapy) into or near the tumor resection cavity. The injection will be done at the time of surgery. HSV1716 is a virus that has a gene which has been changed or removed (mutated) in such a way that lets the virus multiply in dividing cells of the tumor and kills the tumor cells.
Full description
PRIMARY OBJECTIVES:
I. To determine whether intratumoral/peritumoral injection of HSV1716 (oncolytic HSV-1716) is safe in children with recurrent high-grade gliomas amenable to resection.
II. To estimate the maximum tolerated dose (MTD) or a recommended Phase II dose of intratumoral/peritumoral injection of HSV1716.
III. To describe any dose-limiting toxicities (DLT) of intratumoral/peritumoral injection of HSV1716 at the doses given to children with high-grade gliomas.
IV. To evaluate changes in tumor enhancement, quantitative magnetic resonance (MR) measures of tumor perfusion (relative cerebral blood volume [rCBV], transfer coefficient [k^trans], fractional blood-plasma volume [Vp] and extravascular extracellular space per unit volume tissue [Ve] values and apparent diffusion coefficient [ADC]) in response to HSV1716 injection.
SECONDARY OBJECTIVES:
I. To measure antiviral immune response in patients with refractory high-grade gliomas injected with HSV1716.
II. To measure the systemic viremia and viral shedding following intratumoral/peritumoral administration of HSV1716.
III. To preliminarily describe the antitumor activity of HSV1716 injection within the confines of a Phase I study.
IV. To evaluate anti-tumor immune cellular and humoral immune responses. V. To evaluate changes in fluorodeoxyglucose (FDG)- positron emission tomography (PET) uptake in response to HSV1716 injection.
VI. To evaluate changes in tumor choline values using magnetic resonance (MR) spectroscopy in response to HSV1716 injection and further delineate from progressive disease versus pseudo-progression post therapy.
OUTLINE: This is a dose-escalation study.
Patients receive oncolytic HSV-1716 intratumorally (IT) and peritumorally after undergoing surgical tumor resection. Patients also receive dexamethasone intravenously (IV) prior to and 6 and 12 hours after surgery.
After completion of study treatment, patients are followed up every 2 months for 1 year, every 6 months for 4 years, and then annually for 10 years.
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Inclusion criteria
Imaging evaluations necessary to establish eligibility for study entry must be done within three (3) weeks prior to registration; all other evaluations necessary to establish eligibility for study entry must be done within two (2) weeks prior to registration; in the event that the patient's condition deteriorates (performance score < 60) within 48 hours prior to the injection the patient is no longer eligible to receive HSV1716 injection
Patients must have a histologically-confirmed primary diagnosis of high-grade glioma (HGG) (such as glioblastoma multiforme, gliosarcoma, anaplastic oligodendroglioma, anaplastic ganglioglioma, high grade astrocytoma, not otherwise specified [NOS]) that is recurrent or refractory to conventional therapy; patients with metastatic disease are not eligible
Patients must be those for whom surgical resection is clinically indicated; the intent of surgical resection may include debulking or attempt to resect as much of the tumor as safely feasible; if a gross total or near total resection is not feasible, HSV1716 injection into the wall of the resection cavity, encompassing residual tumor, is permissible
Patients must be amenable to receiving 1 dose of HSV1716 intra-operatively with planned HSV1716 injection sites >= 1 cm from the ventricular system AND meet at least one of the criteria below based upon pre-surgical magnetic resonance imaging (MRI):
An intraoperative MRI upon resection will confirm the distance of the planned injection sites from the ventricular system prior to the HSV1716 injection; intra-operatively, the neurosurgeon may decide to not inject the HSV1716 or may revise the sites of HSV1716 injection if injection cannot be guaranteed >= 1 cm from the ventricular system; patient will removed from the study if there are not sufficient areas in the tumor cavity to guarantee injection of HSV1716 >= 1 cm from the ventricular system
Patients must have received prior therapy other than surgery and must have fully recovered from the acute treatment related toxicities of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
Patients must have received their last dose of known myelosuppressive anticancer chemotherapy at least three (3) weeks prior to study registration treatment or at least six (6) weeks if nitrosourea
Investigational/Biologic agent:
Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent >= 7 days prior to study registration
Monoclonal antibody treatment: At least three half-lives must have elapsed prior to registration; Note: A list of the half-lives of commonly used monoclonal antibodies is available on the Pediatric Brain Tumor Consortium (PBTC) webpage under Generic Forms and Templates
Patients must have had their last fraction of:
Patient must be:
Karnofsky performance scale (KPS for > 16 years of age) or Lansky performance score (LPS for =< 16 years of age) assessed within two weeks of registration must be >= 60
Hemoglobin: >= 10 g/dl
Absolute neutrophil count: >= 1000/mm^3
Platelets: >= 100,000/mm^3 (transfusion independent defined as not receiving platelet transfusions within 7 days prior to registration)
Total bilirubin: < 1.5 x upper limit of institutional normal for age
Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]): =< 2.5 × institutional upper limit of normal
Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age and gender as follows:
Albumin >= 2.5 g/dL
Partial thromboplastin time (PTT) < 1.2 X institutional upper limits of normal
Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration; this is to be documented at baseline
Patients with central nervous system (CNS) tumors who are receiving dexamethasone must have been on a stable or decreasing dose of dexamethasone for the 7 days prior to enrollment
Growth factors that support platelet or white cell number or function must not have been administered within the past 7 days; growth factors include: GCSF (filgrastim), PEG-GCSF (Neulasta), GM-CSF (sargramostim) and erythropoietin
Documented evidence of negative tests for the presence of hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus (HIV)1/2 antibodies within the three months preceding study entry; subjects who do not have such evidence must undergo appropriate testing prior to virus administration; HIV-positive patients on combination antiretroviral therapy are ineligible
Female patients of childbearing potential must have a negative serum or urine pregnancy test at the time of enrollment
Ability to understand and the willingness to sign a written informed consent document according to institutional guidelines
Exclusion criteria
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2 participants in 1 patient group
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Data sourced from clinicaltrials.gov
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