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

NCT02031965 | Terminated Phase 1

• 3 other identifiers: PBTC-037NCI-2013-00526U01CA081457
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  56 days

Secondary Outcomes (8)

• Antiviral immune responses

  Up to 15 years

• Systemic viremia and viral shedding

  Up to 15 years

• Progression free survival

  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

  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)

  Baseline up to 2 months post-injection

Study Arms (1)

Treatment (oncolytic HSV-1716)

EXPERIMENTAL

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; Drug: dexamethasone; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis

Interventions

oncolytic HSV-1716 BIOLOGICAL

Given IT

Also known as: herpes simplex virus 1716

Treatment (oncolytic HSV-1716)

dexamethasone DRUG

Given IV

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Treatment (oncolytic HSV-1716)

therapeutic conventional surgery PROCEDURE

Undergo surgical resection

Treatment (oncolytic HSV-1716)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (oncolytic HSV-1716)

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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):
• Tumor is \>= 1 cm from the ventricular system
• Patients whose tumors that are =\< 1 cm from the ventricular system are eligible if there is sufficient space within the tumor cavity and/or residual tumor to perform the HSV 1716 injections that are \>= 1 cm from the ventricular system
• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pediatric Brain Tumor Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

MeSH Terms

Conditions

Astrocytoma; Oligodendroglioma; Glioblastoma; Neoplasms, Neuroepithelial

Interventions

Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Glioma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Mariko DeWire

  Pediatric Brain Tumor Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2014
• First Posted: January 9, 2014
• Study Start: December 1, 2013
• Primary Completion: May 1, 2016
• Study Completion: May 1, 2016
• Last Updated: May 30, 2016

Record last verified: 2016-05

Locations

US (1)