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

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ClinicalTrials.gov Identifier: NCT01766739
Recruitment Status : Active, not recruiting
First Posted : January 11, 2013
Last Update Posted : January 18, 2019
Sponsor:
Collaborator:
Genelux Corporation
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE January 9, 2013
First Posted Date  ICMJE January 11, 2013
Last Update Posted Date January 18, 2019
Study Start Date  ICMJE January 2013
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2013)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 9, 2013)
Maximum Tolerated Dose (MTD) [ Time Frame: 2 years ]
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.
Change History Complete list of historical versions of study NCT01766739 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 7, 2014)
  • 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).
  • 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.
  • 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).
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 9, 2013)
  • 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).
  • detection of virus in body fluids [ Time Frame: days 2 and 3 after treatment ]
    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 and 3 after treatment.
  • evaluation of viral appearance in tumor [ Time Frame: 2-7 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 GFPdirected biopsies will be performed to allow for assessment of viral presence. Viral plaque assays (VPA) will be performed in tumor biopsies and pleural drainage to confirm viral titers. Immunohistochemical (IHC) staining for GL-ONC1 will be performed on both GFP (-) and (+) areas at videothoracoscopy
  • Therapeutic efficacy [ Time Frame: day 60 post treatment ]
    Therapeutic efficacy will be investigated with CT scans pretreatment and at Day 60 posttreatment. Response by RECIST criteria (and by modified RECIST - for mesothelioma tumors) will be summarized for each dose level using descriptive statistics.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intra-pleural Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Malignant Pleural Effusion: Primary, Metastases and Mesothelioma
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lung Cancer
Intervention  ICMJE Biological: GL-ONC1
Patients will be enrolled in groups of three and individually assessed for safety and dose limiting toxicity (DLT).
Study Arms  ICMJE 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.
Intervention: Biological: GL-ONC1
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 27, 2017)
18
Original Estimated Enrollment  ICMJE
 (submitted: January 9, 2013)
54
Estimated Study Completion Date  ICMJE January 2020
Estimated Primary Completion Date January 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01766739
Other Study ID Numbers  ICMJE 12-169
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE Genelux Corporation
Investigators  ICMJE
Principal Investigator: Valerie Rusch, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP