Oncolytic HSV-1716 in Treating Younger Patients With Refractory or Recurrent High Grade Glioma That Can Be Removed By Surgery
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|ClinicalTrials.gov Identifier: NCT02031965|
Recruitment Status : Terminated
First Posted : January 9, 2014
Last Update Posted : May 30, 2016
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Childhood Anaplastic Astrocytoma Recurrent Childhood Anaplastic Oligoastrocytoma Recurrent Childhood Anaplastic Oligodendroglioma Recurrent Childhood Giant Cell Glioblastoma Recurrent Childhood Glioblastoma Recurrent Childhood Gliomatosis Cerebri Recurrent Childhood Gliosarcoma||Biological: oncolytic HSV-1716 Drug: dexamethasone Procedure: therapeutic conventional surgery Other: laboratory biomarker analysis||Phase 1|
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.
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 (Clinical Trial)|
|Actual Enrollment :||2 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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)|
|Study Start Date :||December 2013|
|Actual Primary Completion Date :||May 2016|
|Actual Study Completion Date :||May 2016|
Experimental: Treatment (oncolytic HSV-1716)
Patients receive oncolytic HSV-1716 IT and peritumorally after undergoing surgical tumor resection. Patients also receive dexamethasone IV prior to and 6 and 12 hours after surgery.
Biological: oncolytic HSV-1716
Other Name: herpes simplex virus 1716Drug: dexamethasone
Other Names:Procedure: therapeutic conventional surgery
Undergo surgical resectionOther: laboratory biomarker analysis
- 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.
- 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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02031965
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|Principal Investigator:||Mariko DeWire||Pediatric Brain Tumor Consortium|