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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
2
Given IT
Given IV
Undergo surgical resection
Correlative studies
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
MTD of oncolytic HSV-1716, defined as the highest dose level at which 0 out of 3 or at most one out of 6 patients have been treated experiencing a dose limiting toxicity and the next higher dose level has been determined to be too toxic
Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
Time frame: 56 days
Antiviral immune responses
Summarized and reported descriptively.
Time frame: Up to 15 years
Systemic viremia and viral shedding
Summarized and reported descriptively.
Time frame: Up to 15 years
Progression free survival
Time frame: From the date of initial protocol treatment to the earliest date of disease progression, second malignancy or death for patients who fail; and to the date of last contact for patients who remain at risk for failure, assessed up to 15 years
Overall survival
Time frame: From the date of initial protocol treatment to the date of death for patients who fail; and to the date of last contact for patients who remain at risk for failure, assessed up to 15 years
Changes in MR parameters (including diffusion and perfusion studies) (optional)
Summary statistics and graphs used to describe changes in these quantitative imaging parameters.
Time frame: Baseline up to 2 months post-injection
Changes in MRS and PET parameters (including diffusion and perfusion studies) (optional)
Summary statistics and graphs used to describe changes in these quantitative imaging parameters.
Time frame: Baseline up to 2 months post-injection
Anti-tumor cellular responses
Time frame: Up to week 16
Humoral immune responses
Time frame: Up to week 16
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.