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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Pediatric Brain Tumor Consortium
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier:
NCT02031965
First received: January 7, 2014
Last updated: NA
Last verified: January 2014
History: No changes posted
  Purpose

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.


Condition Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Pediatric Brain Tumor Consortium:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.


Secondary Outcome Measures:
  • Antiviral immune responses [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
    Summarized and reported descriptively.

  • Systemic viremia and viral shedding [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Changes in MR parameters (including diffusion and perfusion studies) (optional) [ Time Frame: Baseline up to 2 months post-injection ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Summary statistics and graphs used to describe changes in these quantitative imaging parameters.

  • Anti-tumor cellular responses [ Time Frame: Up to week 16 ] [ Designated as safety issue: No ]
  • Humoral immune responses [ Time Frame: Up to week 16 ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: December 2013
Estimated Primary Completion Date: February 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Given IT
Other Name: herpes simplex virus 1716
Drug: dexamethasone
Given IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Procedure: therapeutic conventional surgery
Undergo surgical resection
Other: laboratory biomarker analysis
Correlative studies

Detailed 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.

  Eligibility

Ages Eligible for Study:   16 Years to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 and are amenable to receiving 1 dose of HSV1716 into the periphery of the tumor cavity and within the residual disease if present during their resection without risk of intra-ventricular injection; patients whose tumors are within at least 1 cm of the ventricle are not eligible for this study; 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 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

      • For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
    • 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:

    • Craniospinal irradiation (> 24 Gray [Gy]) or total body irradiation > 3 months prior to registration
    • Focal irradiation to symptomatic metastatic sites > 4 weeks prior to registration
    • Local palliative external beam radiation therapy (XRT) (small port) >= 4 weeks
    • If prior total-body irradiation (TBI), craniospinal XRT or if >= 50% radiation of pelvis >= 6 months must have elapsed
    • If other substantial bone marrow (BM) radiation >= 6 weeks must have elapsed
  • Patient must be:

    • >= 6 months since allogeneic bone marrow transplant prior to registration
    • Stem cell transplant or rescue without TBI: No evidence of active graft vs. host disease and >= 3 months must have elapsed since transplant
  • 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:

    • Age 2 to < 6 years: maximum serum creatinine (mg/dL): 0.8 for males and 0.8 for females
    • Age 6 to < 10 years: maximum serum creatinine (mg/dL): 1 for males and 1 for females
    • Age 10 to < 13 years: maximum serum creatinine (mg/dL): 1.2 for males and 1.2 for females
    • Age 13 to < 16 years: maximum serum creatinine (mg/dL): 1.5 for males and 1.4 for females
    • Age >= 16 years: maximum serum creatinine (mg/dL): 1.7 for males and 1.4 for females
  • 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:

  • Patients with metastatic disease i.e. leptomeninges, multi-focal lesions in the CNS
  • Patients whose tumor lies within 1 cm of the ventricular system
  • Patients who are receiving any other investigational agents
  • Patients who are currently receiving other anti-cancer agents are excluded from this trial
  • Patients with history of prior HSV encephalitis or encephalitis due to other etiologies
  • There is no available information regarding human fetal or teratogenic toxicities
  • Pregnant women are excluded to avoid the risk of systemic intrauterine/neonatal HSV infection
  • Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method from the time of study entry to a period of no less than four months post the HSV1716 injection
  • Women who participate in this study must agree not to breastfeed from study entry to a period of no less than four months post the HSV1716 injection
  • Subjects whose primary physicians determine that anti-HSV antiviral therapy (such as acyclovir, ganciclovir, foscarnet, etc.) cannot be safely discontinued from 2 days prior to the injection to 28 days following the injection are excluded from this study
  • Patients on systemic anticoagulants are excluded from this study
  • Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that would compromise the patient's ability to tolerate protocol therapy or would likely interfere with the study procedures or results
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02031965

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Mariko D. DeWire, M.D.    513-636-4266    mariko.dewire@cchmc.org   
Contact: Timothy Cripe, M.D.    614-722-3552    timothy.cripe@nationwidechildrens.org   
Principal Investigator: Mariko D. DeWire         
Sponsors and Collaborators
Pediatric Brain Tumor Consortium
Investigators
Principal Investigator: Mariko DeWire Pediatric Brain Tumor Consortium
  More Information

No publications provided

Responsible Party: Pediatric Brain Tumor Consortium
ClinicalTrials.gov Identifier: NCT02031965     History of Changes
Other Study ID Numbers: PBTC-037, NCI-2013-00526, PBTC-037, PBTC-037, U01CA081457
Study First Received: January 7, 2014
Last Updated: January 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Astrocytoma
Glioblastoma
Oligodendroglioma
Gliosarcoma
Neoplasms, Neuroepithelial
Glioma
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 24, 2014