A Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2

  • STATUS
    Recruiting
  • End date
    Dec 21, 2023
  • participants needed
    56
  • sponsor
    Dana-Farber Cancer Institute
Updated on 21 August 2021
cyclophosphamide
ependymoma
MRI
cytotoxic chemotherapy
experimental drug
neutrophil count
bevacizumab
aptt
temozolomide
astrocytoma
malignant glioma
brain tumor
oligodendroglioma
low grade glioma
anaplastic oligodendroglioma
astrocytoma, anaplastic
oligoastrocytoma
therapeutic agent
recurrent malignant glioma
oligodendroglioma, anaplastic
ganglioglioma
absolute lymphocyte count
stereotactic biopsy
immunotherapeutic agent

Summary

This research study is evaluating an investigational drug, an oncolytic virus called rQNestin34.5v.2. This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug as a possible treatment for this diagnosis of recurrent or progressive brain tumor.

Description

This research study is a Phase I clinical trial, which tests the safety of an investigational drug and also tries to define the appropriate dose of the investigational drug as a possible treatment for this diagnosis. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has not approved rQNestin34.5v.2 as a treatment for any disease. This is the first time that rQnestin34.5v.2 will be given to humans.

The research drug, rQNestin34.5v.2, is an oncolytic viral vector made from the herpes simplex virus type 1 (HSV1). The large majority of humans already have regular HSV1 in their nervous system. Normally, this virus can cause cold sores in areas like the lips, fingers and genitals in humans by making copies of itself in normal healthy cells. In some cases, HSV1 can cause severe infection of the brain and liver and/or death. However, scientists have removed or changed parts of the rQNestin virus being used on this study so it can only make copies of itself in glioma cells and not normal healthy cells.

If it is effective, the rQNestin34.5v.2 drug will spread to a glioma cell, kill it, and then make a copy of itself and spread again. This should be repeated over and over until all glioma cells are reached. If rQNestin34.5v.2 moves into a normal brain cell, it should not grow and make copies, and therefore should not spread to other normal brain cells.

The purpose of this research study is to test if rQnestin34.5v.2 is safe to use in humans, and if it is effective in treating malignant glioma. This study is also looking for the highest dose of rQNestin34.5v.2 that can be given safely to people with malignant brain tumors.

Details
Condition Ependymoma, Oligodendroglioma, Astrocytoma, Glioma, Glioblastoma Multiforme, Malignant neoplasm of brain, Ganglioglioma, Brain Tumor (Pediatric), Malignant Glioma of Brain, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma, Brain Cancer, Gliomas, Brain Tumor, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma, glioblastoma, gangliogliomas, astrocytoma, anaplastic, malignant brain tumor, glial tumor, brain tumors, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma, Anaplastic Oligodendroglioma of Brain (Diagnosis), Pylocytic/Pylomyxoid Astrocytoma
Treatment cyclophosphamide, rQNestin34.5v.2, Stereotactic biopsy, rQNestin
Clinical Study IdentifierNCT03152318
SponsorDana-Farber Cancer Institute
Last Modified on21 August 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

At the time of surgery, frozen biopsy confirmation of high grade or malignant glioma by neuropathologist. Biopsy confirmation of glioma or infiltrative glioma at time of surgery will be acceptable, provided that subject has prior pathology confirmation of high-grade glioma. If subject had previous diagnosis of low grade glioma, then the biopsy must show high grade glioma. To be confirmed at time of surgery, after registration in OnCore
Participants must have prior diagnosis of glioma (astrocytoma, malignant astrocytoma, oligodendroglioma, anaplastic oligodendroglioma, mixed oligo-astrocytoma), exclusive of ependymoma, ganglioglioma, pylocytic/pylomyxoid astrocytoma as confirmed by a neuropathologist or by a previous local pathology report
Prior history of external beam radiotherapy 5,000 cGy delivered to the tumor at least 4 weeks prior to registration. Participants over the age of 70 with prior history of hypofractionated external beam radiotherapy will also be accommodated, in accordance with NCCN guidelines; For participants with diagnosis of oliogodendroglioma or anaplastic oligodendroglioma, prior history of external beam radiotherapy < 5,000 cGy or no history of radiation are both acceptable
Prior history of temozolomide chemotherapy provided concurrent to external beam radiotherapy and after as per current standard of care. However, temozolomide would not be required to have been provided concomitantly or after radiation if the patient had unmethylated MGMT promoter or if the patient initially was diagnosed with a low grade glioma. At least 4 weeks must have passed from the last dose of temozolomide and first dose of cyclophosphamide and/or rQNestin34.5v.2; [3.1.4.1](telnet://3.1.4.1) For participants with diagnosis of oliogodendroglioma or anaplastic oligodendroglioma, chemotherapy may have been administered before, during, or after radiation or not at all
If participant was treated with bevacizumab, at least 4 weeks must elapse before treatment with either agent (Cyclophosphamide or rQNestin34.5v.2)
Recurrent lesion must be 1.0 cm in diameter as determined by MRI
Normal hematological, renal and liver function as defined below: Leukocytes 3,000/mcL; Absolute lymphocyte count > 500/ mcL; Absolute neutrophil count 1,500/mcL; platelets 100,000/mcL; PT or PTT <1.5 x institutional upper limit; Hemoglobin >10.0 g/dL; Total serum bilirubin within normal institutional limits; AST(SGOT)/ALT(SGPT) 2.5 institutional upper limit of normal; Serum creatinine within normal institutional limits OR Creatinine clearance 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal
Karnofsky Performance Score 70
Age 18 years
Ability to understand and the willingness to sign a written informed consent document
The effects of rQNestin34.5v.2 and cyclophosphamide on the developing human fetus are unknown. For this reason and because cytotoxic & immunomodulating agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation including 3 months following the study. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation including 3 months following the study. Women of child-bearing potential must have a negative serum pregnancy test within 48 hours of study registration
Steroid regimen stable or decreasing for at least 7 days prior to inoculation
Ability to undergo MRI scanning with contrast
Subjects with any recurrence (first, second, third, etc recurrence) will be able to be enrolled

Exclusion Criteria

Participants who exhibit any of the following conditions prior to initiating
study treatment will not be eligible for this study
Participants with significant renal or liver disease
Participants with progressive systemic malignancy
Known chronic infections with HIV, hepatitis B or C; participants with a history of resolved Hepatitis A may be included in the trial
Participants with active viral, bacterial or fungal infection requiring concurrent antiviral or antibiotics
Subjects with active HSV1 infection on current valacyclovir, acyclovir or ganciclovir therapy must be off treatment with any of these agents at least 7 days prior to surgery
History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide (only for arm B)
Active, known, or suspected immunosuppressive disorders, such as acquired or congenital immune deficiency syndromes and autoimmune diseases
Unacceptable anesthesia risk
Serious cardiopulmonary medical condition
Pregnant or lactating females
Recurrent glioma where injection in either arm A or B of the biologic agent would require access and/or considerable spillage into the ventricular system
Prior participant in another protocol using an investigational agent or device within 5 half-lives or 4 weeks of the investigational agent, whichever is shorter
Known HIV seropositivity
Concurrent therapy with drugs active against HSV (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir). Participants must be off treatment with these agents for at least 7 days prior to surgery
Active oral or genital herpes lesions
Participants who have had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
Participants who are receiving any other investigational agents. Previous rQNestin34.5v.2 participants may be re-enrolled if they completed at least the day 56 assessment without DLT
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Participants with tumor 1 cm proximity to the ventricles will be allowed to enroll. However the study agent (rQNestin34.5v.2) may not be injected in any area that is within 1 cm of the ventricle regardless of where the tumor is located
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