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

NCT01766739 | Completed Phase 1

• 1 other identifier: 12-169
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer

Keywords

GL-ONC1; pleural effusion; 12-169

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  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 Outcomes (4)

• safety

  2 years

• detection of virus in body fluids

  days 2, 3, 4, & 5. pretreatment

• evaluation of viral appearance in tumor

  2-9 days after intrapleural instillation of virus

• Therapeutic efficacy

  day 60 post treatment (+/-10 days)

Study Arms (1)

GL-ONC1

EXPERIMENTAL

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

Interventions

GL-ONC1 BIOLOGICAL

Patients will be enrolled in groups of three and individually assessed for safety and dose limiting toxicity (DLT).

GL-ONC1

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Genelux Corporation: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• Chintala NK, Choe JK, McGee E, Bellis R, Saini JK, Banerjee S, Moreira AL, Zauderer MG, Adusumilli PS, Rusch VW. Correlative analysis from a phase I clinical trial of intrapleural administration of oncolytic vaccinia virus (Olvi-vec) in patients with malignant pleural mesothelioma. Front Immunol. 2023 Feb 16;14:1112960. doi: 10.3389/fimmu.2023.1112960. eCollection 2023.

  PMID: 36875061 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lung Neoplasms; Pleural Effusion

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pleural Diseases

Study Officials

• Valerie Rusch, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 9, 2013
• First Posted: January 11, 2013
• Study Start: January 1, 2013
• Primary Completion: October 24, 2024
• Study Completion: October 24, 2024
• Last Updated: October 26, 2024

Record last verified: 2024-10

Locations

US (1)