Intra-pleural Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Malignant Pleural Effusion: Primary, Metastases and Mesothelioma
Verified April 2014 by Memorial Sloan-Kettering Cancer Center
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
First received: January 9, 2013
Last updated: April 10, 2014
Last verified: April 2014
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.
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||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
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 and 3 after treatment ] [ 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 and 3 after treatment.
- evaluation of viral appearance in tumor [ Time Frame: 2-7 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) staining for GL-ONC1 will be performed on both GFP (-) and (+) areas at videothoracoscopy (if applicable).
- Therapeutic efficacy [ Time Frame: day 60 post treatment ] [ Designated as safety issue: No ]
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.
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||January 2015 (Final data collection date for primary outcome measure)
This is an open-label, dose-escalating, non-randomized, single-center phase I study to determine the dose recommended for further evaluation of the genetically modified vaccinia virus GL-ONC1 when administered intrapleurally as a single dose to patients with malignant pleural effusion.
Patients will be enrolled in groups of three and individually assessed for safety and dose limiting toxicity (DLT).
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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 anesthesia was administered, must have occurred at least 14 days prior to study enrollment.
- Chemotherapy, radiotherapy or immunotherapy must have stopped more than 14 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.
- 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.
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
|Contact: Valerie Rusch, MD
|Contact: Lee Krug, MD
|Memorial Sloan-Kettering Cancer Center
|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 |
Memorial Sloan-Kettering Cancer Center
||Valerie Rusch, MD
||Memorial Sloan-Kettering Cancer Center
No publications provided
||Memorial Sloan-Kettering Cancer Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||January 9, 2013
||April 10, 2014
||United States: Food and Drug Administration
Keywords provided by Memorial Sloan-Kettering Cancer Center:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 22, 2014
Pleural Effusion, Malignant
Respiratory Tract Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
DNA Virus Infections