Clinical Trial: Oncolytic HSV-1716 in Treating Younger Patients With Refractory or Recurrent High Grade Glioma That Can Be Removed By Surgery

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Phase I Study of Intratumoral/Peritumoral Herpes Simplex Virus-1 Mutant HSV1716 in Patients With Refractory or Recurrent High Grade Gliomas (HGG)

Brief Summary: 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.

Detailed Summary:

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 value
Sponsor: Pediatric Brain Tumor Consortium

Current Primary Outcome: 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 [ Time Frame: 56 days ]

Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Antiviral immune responses [ Time Frame: Up to 15 years ]
    Summarized and reported descriptively.
  • Systemic viremia and viral shedding [ Time Frame: Up to 15 years ]
    Summarized and reported descriptively.
  • 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) [ Time Frame: Baseline up to 2 months post-injection ]
    Summary statistics and graphs used to describe changes in these quantitative imaging parameters.
  • Changes in MRS and PET parameters (including diffusion and perfusion studies) (optional) [ Time Frame: Baseline up to 2 months post-injection ]
    Summary statistics and graphs used to describe changes in these quantitative imaging parameters.
  • Anti-tumor cellular responses [ Time Frame: Up to week 16 ]
  • Humoral immune responses [ Time Frame: Up to week 16 ]


Original Secondary Outcome: Same as current

Information By: Pediatric Brain Tumor Consortium

Dates:
Date Received: January 7, 2014
Date Started: December 2013
Date Completion:
Last Updated: May 26, 2016
Last Verified: May 2016