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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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Genelux Corporation
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01766739
First received: January 9, 2013
Last updated: October 7, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Biological: GL-ONC1
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 34
Study Start Date: January 2013
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01766739

Contacts
Contact: Valerie Rusch, MD 212-639-5873
Contact: Lee Krug, MD 646-888-4201

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Valerie Rusch, MD    212-639-5873      
Contact: Lee Krug, MD    646-888-4201      
Principal Investigator: Valerie Rusch, MD         
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Genelux Corporation
Investigators
Principal Investigator: Valerie Rusch, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01766739     History of Changes
Other Study ID Numbers: 12-169
Study First Received: January 9, 2013
Last Updated: October 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
GL-ONC1
pleural effusion
12-169

Additional relevant MeSH terms:
Mesothelioma
Neoplasms, Mesothelial
Pleural Effusion
Pleural Effusion, Malignant
Vaccinia
Adenoma
DNA Virus Infections
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Pleural Diseases
Pleural Neoplasms
Poxviridae Infections
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Virus Diseases

ClinicalTrials.gov processed this record on November 20, 2014