Trial of C134 in Patients With Recurrent GBM

NCT03657576 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: IRB-3000000571R01CA222903
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this project is to obtain safety information in small groups of individuals, scheduled to receive escalating doses of C134, a cancer killing virus (HSV-1) that has been genetically engineered to safely replicate and kill glioma tumor cells. Safety will be assessed at each dose level before proceeding to the next dose level. A special statistical technique called the Continual Reassessment Method (CRM) will be used to determine when higher doses of virus can be administered. Other objectives of the study include characterization of the activity of C134 after inoculation into the tumor and of the local and systemic immune responses to C134. Patients will also be followed with MRI scans for potential clinical response to C134. The clinical strategy takes advantage of the virus' ability to infect and kill tumor cells while making new virus within the tumors cells; a critical enhancement of this effect is accomplished by the induction of an anti-tumor immune response; both effects are produced by the IRS-1 gene that was placed into the virus by genetic engineering. An additional important component of the research are systematic assessments of the quality of life on treated patients.

Conditions

Glioblastoma Multiforme of Brain; Anaplastic Astrocytoma of Brain; Gliosarcoma of Brain

Keywords

oncolytic virus; glioma; glioblastoma; GBM; HSV; immunotherapy; Brain Tumors

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of C134 Treatment

  Dose modifications will utilize a modified Continual Reassessment Method (CRM) for each successive subject until an MTD or the maximal planned dose is reached.

  from baseline through month 12

Secondary Outcomes (5)

• Measure of Progression Free Survival

  pre-study, day 3, day 28, month 3, month 6, month 12

• Measure Overall Survival

  day 0, day 1, day 2, day 3, day 7, day 28, month 3, month 6, month 12

• Measurement of HSV Titer

  pre-study, day 28, month 3, month 6, month 12

• Composition of the White Blood Cells

  pre-study, day 2, day 7, day 28, month 3, month 6, month 12

• Measure Interferon Levels

  pre-study, day 2, day 7, day 28, month 3, month 6, month 12

Study Arms (1)

C134 Treatment

EXPERIMENTAL

All patients who enroll will receive C134 inoculation into their tumor (one time procedure with 1-5 inoculation sites)

Biological: C134

Interventions

C134 BIOLOGICAL

C134 is a virus that was created from an oncolytic Herpes Simplex Virus (oHSV) known to infect and kill tumor cells. The Investigators have made changes to the original virus to make C134. It efficiently infects tumor cells (not normal healthy cells) and induces an immune response to fight the cancer as well.

C134 Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed recurrent/progressive glioblastoma multiforme, anaplastic astrocytoma, or gliosarcoma.
• Prior therapy. Patients must have failed external beam radiotherapy to the brain at least 4 weeks prior to enrollment.
• Age 18 years or older, because no dosing or adverse event data are currently available on the use of IRSl-chimeric HSVl in patients below 18 years of age, children are excluded from this study but will be eligible for future pediatric phase 1 single-agent trials. Note: 18 is the age of majority in the state of Alabama for participation in clinical trials.
• Karnofsky Performance Status ≥70%
• Life expectancy of greater than 4 weeks.
• Patients must have normal organ and marrow function as defined below:
• leukocytes ≥3,000/uL
• absolute neutrophil count ≥1,500/uL
• platelets ≥100,000/uL
• total bilirubin within normal institutional limits
• AST(SGOT)/ ALT(SGPT) ≤2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits OR Creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels
• Residual lesion must be ≥1.0 and \< 5.5 cm in diameter without bilateral extension through the corpus callosum as determined by MRI as this is a locally delivered treatment. These parameters will be re-evaluated on imaging done on the day of catheter implantation and if the lesion no longer meets the criteria, the patient will not undergo catheter implantation or treatment with C134.
• The effects of IRS1-chimeric HSV1 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the first six months after receiving IRS1-chimeric HSVl. Because it is currently unknown if IRS1-chimeric HSV1 can be transmitted by sexual contact, a barrier method of birth control should be employed. Should a woman become pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document (Informed consent document in Appendix E).

You may not qualify if:

• Patients who have had chemotherapy, cytotoxic therapy, immunotherapy or gene therapy within 6 weeks prior to entering the study, surgical resection within 4 weeks prior to entering the study, or have received experimental viral therapy at any time (e.g., adenovirus, retrovirus or herpesvirus \* protocol). Also, those who have not recovered from adverse events due to therapeutic interventions administered more than 4 weeks earlier.
• Patients may not be receiving any other investigational agents.
• History of allergic reactions attributed to compound of similar biologic composition to IRS1-chimeric HSVl.
• Tumor involvement which would require ventricular, brainstem, basal ganglia, or posterior fossa inoculation or would require access through a ventricle in order to deliver treatment.
• Prior history of encephalitis, multiple sclerosis, or other CNS infection.
• Required steroid increase within 2 weeks of scheduled IRS1-chimeric HSV1 administration.
• Active oral herpes lesion.
• Concurrent therapy with any drug active against HSV (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet, cidofovir).
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or any other medical condition that precludes surgery . Also, psychiatric illness/social situations that would limit compliance with study requirements.
• Required steroid increase within 2 weeks of scheduled C134 administration. When possible, the patient should be on a dexamethasone equivalent dose of ≤2mg daily at the time of treatment.
• Known history of allergic reaction to IV contrast material that is not amenable to pre-treatment by UAB protocol.
• Have a pacemaker, ferro-magnetic aneurysm clips, metal infusion pumps, metal or shrapnel fragments, or certain types of stents.
• Received Bevacizumab (Avastin) therapy within 4 weeks of scheduled C134 administration.
• Excluded patient groups
• Pregnant women are excluded from this study because IRS1-chimeric HSV1 is a viral oncolytic therapy with unknown potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with IRS1-chimeric HSV1, breastfeeding should be discontinued if the mother is treated with IRS1-chimeric HSVl.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Gateway for Cancer Research: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Glioma; Glioblastoma; Brain Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: James Markert, MD
• Organization: The University of Alabama at Birmingham

jmarkert@uabmc.edu

2059347171

Study Officials

• James Markert, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Modified continuous reassessment model (mCRM). Using this statistical method, dose changes occur based upon toxicities (or lack thereof) observed after a 24 day observation period for the initial dose level. If toxicities occurring at any dose were acceptable, doses for subsequent cohorts can be increased by up to 1 log until a maximum tolerated dose is reached. If toxicities are unacceptable then dose de-escalation occurs until a safe acceptable maximum tolerated dosage is defined. However, it should be noted that the dose alterations are not predictable and cannot be predefined, they are statistically determined after each patient using mCRM software.

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: September 5, 2018
• Study Start: September 23, 2019
• Primary Completion: October 25, 2024
• Study Completion (Estimated): September 1, 2026
• Last Updated: August 3, 2025
• Results First Posted: July 3, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)