Intra-pleural Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Malignant Pleural Effusion: Primary, Metastases and Mesothelioma

October 24, 2024 updated by: Memorial Sloan Kettering Cancer Center

Phase I Study of Intra-pleural Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Malignant Pleural Effusion: Primary, Metastases and Mesothelioma

The purpose of this study is to test the safety of the GL-ONC1 vaccinia virus at different dose levels. The investigators want to find out what effects, good and/or bad, it has on the patient and the malignant pleural effusion. A malignant pleural effusion is a build up of fluid in the chest cavity cause by the cancer.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of histologically or cytologically documented, malignant pleural effusions (primary non-small-cell lung carcinoma, mesothelioma, and other histologies), who have free pleural space (partial or total) that permits the intrapleural drug instillation. This includes cytologically negative pleural effusion in conjunction with histologically proven malignancy involving the pleura.
  • Age must be ≥ 18 years.
  • All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedures must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0) Grade ≤ 1.
  • Any surgery, where general anesthesia was administered, must have occurred at least 14 days prior to study enrollment.
  • Chemotherapy, radiotherapy or immunotherapy must have stopped more than 7 days prior to receiving study drug; however, small field palliative radiotherapy, TKI therapies and hormonal therapies are allowed.
  • Patients with stage IV malignancy (non-mesothelioma) must have had a brain scan (MRI or CT with contrast) showing no evidence of disease progression within 8 weeks of study enrollment.
  • ECOG Zubrod ≤ 2.
  • Required baseline laboratory data include:
  • Absolute neutrophil count (ANC) ≥ 1.5 × 109 [SI units 10^9/L],
  • Platelets ≥ 100 ×10^9 [SI units 10^9/L],
  • Hemoglobin ≥ 9.0 g/dL [SI units gm/L],
  • Serum creatinine ≤ 1.5 × upper limit of normal (ULN),
  • Bilirubin ≤ 1.5 × ULN,
  • AST/ALT ≤ 2.5 × ULN (≤ 5 × ULN in the presence of liver metastases)
  • Negative pregnancy test for females of childbearing potential.

Exclusion Criteria:

  • Pregnant or breast-feeding women.
  • Patients with fever or any active systemic infections, including known HIV, hepatitis B or C.
  • Patients on immunosuppressive therapy or with immune system disorders, including autoimmune diseases.
  • Concurrent steroid use of more than an equivalent of 20 mg/day prednisone (or equivalent).
  • Prior splenectomy.
  • Previous organ transplant.
  • Patients with clinically significant dermatological disorders, e.g., eczema or psoriasis, as judged by the principal investigator, or any unhealed skin wounds or ulcers.
  • Clinically significant cardiac disease (New York Heart Association, Class III or IV).
  • Dementia or altered mental status that would prohibit informed consent.
  • Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality, that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results and, in the judgment of the principal investigator, would make the patient inappropriate for this study.
  • Known allergy to ovalbumin or other egg products.
  • Prior gene therapy treatments or prior therapy with cytolytic virus of any type.
  • Concurrent therapy with any other investigational anticancer agent.
  • Concurrent antiviral agent active against vaccinia virus (e.g. cidofovir, vaccinia immunoglobulin) during the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: GL-ONC1
This is an open-label, dose-escalating, non-randomized, single-center Phase I therapeutic study of GL-ONC1 originally administered intrapleurally as a single dose and now escalating to three consecutive daily doses in patients with a diagnosis (histologically or cytologically documented) of malignant pleural effusions.
Biological: GL-ONC1
Patients will be enrolled in groups of three and individually assessed for safety and dose limiting toxicity (DLT).

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD)
Time Frame: 2 years
MTD is to provide a dosing recommendation for subsequent Phase II studies. Three patients will be enrolled in each cohort at the dose levels shown in the table below in order to determine the Maximum Tolerated Dose (MTD). At the beginning of a new dose level, only one patient will be treated. The first patient in each cohort must be treated and complete 14 days of post-treatment evaluation prior to the treatment of the remaining two patients in that cohort.
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
safety
Time Frame: 2 years
The safety, tolerability and feasibility of GL-ONC1 will be assessed by the evaluation of the type, frequency, and severity of adverse events (AEs), changes in clinical laboratory tests (hematological and chemistry), immunogenicity and physical examination. All AEs and laboratory toxicities will be graded on the CTCAE (version 4).
2 years
detection of virus in body fluids
Time Frame: days 2, 3, 4, & 5. pretreatment
Patients will undergo serial sampling of blood, sputum, urine samples and pleural drainage for evaluation of viral particles by VPA immediately before treatment, and on days 2, 3, 4 and 5 pretreatment.
days 2, 3, 4, & 5. pretreatment
evaluation of viral appearance in tumor
Time Frame: 2-9 days after intrapleural instillation of virus
Unless medically contraindicated, patients will undergo Video-Assisted Thoracic Surgery (VATS) with pleural biopsies to assess for green fluorescent protein (GFP) viral expression in tumor and surrounding tissues, and if appropriate, to perform pleurodesis at 2-7 days after intrapleural instillation of virus. Random pleural biopsies and GFP-directed biopsies will be performed to allow for assessment of viral presence. Viral plaque assays (VPA) will be performed in tumor biopsies. Immunohistochemical (IHC) and beta-glucuronidase assay staining for GL-ONC1 will be performed on both GFP (-) and (+) areas at videothoracoscopy (if applicable).
2-9 days after intrapleural instillation of virus
Therapeutic efficacy
Time Frame: day 60 post treatment (+/-10 days)
Therapeutic efficacy will be investigated with CT scans pretreatment and at Day 60 (+/-10) posttreatment. Response by RECIST criteria (and by modified RECIST - for mesothelioma tumors) will be summarized for each dose level using descriptive statistics.
day 60 post treatment (+/-10 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Memorial Sloan Kettering Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Genelux Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Valerie Rusch, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 24, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 24, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 9, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 9, 2013

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 11, 2013

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 26, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 24, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 12-169

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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