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Safety and Effect of GL-ONC1 Administered IV With or Without Eculizumab Prior to Surgery to Patients With Solid Organ Cancers Undergoing Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by University of California, San Diego
Sponsor:
Collaborator:
Genelux Corporation
Information provided by (Responsible Party):
Kaitlyn Kelly, MD, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT02714374
First received: March 2, 2016
Last updated: June 17, 2016
Last verified: May 2016
  Purpose
The purpose of this study is to evaluate the safety of the investigational product GL-ONC1 in combination with eculizumab. GL-ONC1, a vaccinia virus, has been genetically modified for use as a potential anti-cancer drug to destroy cancer cells. Vaccinia virus has been used successfully in the past as smallpox vaccine in millions of people worldwide. Eculizumab is a type of drug called a monoclonal antibody. This drug is designed to inhibit the activity of a protein called complement. Complement is part of the body's immune system that destroys and removes foreign particles. Evidence from laboratory tests suggest eculizumab may allow GL-ONC1 to stay in the body longer before being cleared by the immune system, which may help destroy more cancer cells.

Condition Intervention Phase
Solid Organ Cancers
Biological: GL-ONC1
Biological: Eculizumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label, Non-randomized Phase 1b Study to Investigate the Safety and Effect of the Oncolytic Virus GL-ONC1 Administered Intravenously With or Without Eculizumab Prior to Surgery to Patients With Solid Organ Cancers Undergoing Surgery for Curative-Intent or Palliative Resection

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Number of participants with treatment-related adverse events as defined by CTCAE v4.03. [ Time Frame: 2.5 years ]

Secondary Outcome Measures:
  • The presence of GL-ONC1 within malignant tumors by examination of the resected surgical specimen. [ Time Frame: 2.5 years ]
  • The maximum concentration (Cmax) of GL-ONC1 in blood after administration [ Time Frame: 2.5 years ]
  • Level of anti-vaccinia neutralizing antibodies in serum [ Time Frame: 2.5 years ]
  • Amount of lymphocyte infiltration in pre-treatment biopsy and post-treatment resected tumor tissue [ Time Frame: 2.5 years ]

Estimated Enrollment: 36
Study Start Date: March 2016
Estimated Study Completion Date: March 2020
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GL-ONC1 + Eculizumab
Cohort 1, 2, 4, and 6
Biological: GL-ONC1

Dose and Regimen:

  1. Single dose group: Cohort 1 dose is 1 × 109 pfu
  2. Multiple dose groups:

    • Cohort 2 dose is 1 × 109 pfu × 5 consecutive days
    • Cohorts 3 and 4 dose is 2 × 109 pfu × 5 consecutive days
    • Cohorts 5 and 6 dose escalates at 2,3,5,5,5 × 109 pfu.

Route: GL-ONC1 is delivered as a bolus IV injection.

Biological: Eculizumab

Dose and Regimen: With the exception of Cohorts 3 and 5, eculizumab is administered as a single dose on Week 1/Day 1 at 900 mg 60-90 minutes prior to GL-ONC1. For patients undergoing surgery > 10 days following completion of virus treatment, an additional, maintenance dose of Eculizumab (600 mg) may be given 14 to 17 days following administration of the initial eculizumab dose.

Route: Eculizumab is administered intravenously.

Other Name: Soliris
Experimental: GL-ONC1
Cohort 3 and 5
Biological: GL-ONC1

Dose and Regimen:

  1. Single dose group: Cohort 1 dose is 1 × 109 pfu
  2. Multiple dose groups:

    • Cohort 2 dose is 1 × 109 pfu × 5 consecutive days
    • Cohorts 3 and 4 dose is 2 × 109 pfu × 5 consecutive days
    • Cohorts 5 and 6 dose escalates at 2,3,5,5,5 × 109 pfu.

Route: GL-ONC1 is delivered as a bolus IV injection.


Detailed Description:

This is an open-label, non-randomized Phase 1b dose escalation study evaluating the safety and effect of the oncolytic virus GL-ONC1 administered intravenously, with or without eculizumab, prior to surgery in patients with advanced solid organ tumors.

GL-ONC1 has been investigated in early stage clinical trials in the United States and Europe via systemic delivery as monotherapy and in combination with other therapies, and via regional delivery as monotherapy. GL-ONC1 treatment was well tolerated across different malignancies, routes of administration, and monotherapy as well as combination therapy protocols. The ability of GL-ONC1 to infect tumor tissue and kill tumor cells was demonstrated. In addition, virus-induced immune activation and elevation of serum markers linking to a favorable antitumor immune response have been observed.

Eculizumab is a monoclonal antibody designed to inhibit the activity of a protein called complement which is part of the body's innate immune system. Evidence from laboratory tests suggest eculizumab may allow GL-ONC1 to stay in the body longer before being cleared by the immune system.

The goals of this study are to evaluate the safety of concurrent systemic administration of eculizumab and GL-ONC1 and to assess the pharmacokinetics and pharmacodynamics profile of GL-ONC1 in vivo.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically-proven diagnosis of advanced (AJCC, 7th Edition: stage III or IV) or aggressive solid organ cancer.
  • Patients must provide written consent for a core needle biopsy sample of tumor tissue (primary or metastatic).
  • Have evidence of measurable disease (according to RECIST Version 1.1: http:// www.recist.com).
  • Have an ECOG Performance Score of 0 to 2.
  • Have a life expectancy of at least 3 months.
  • Have adequate organ and marrow function
  • Negative serum pregnancy test for females of childbearing potential.
  • Have negative test result for HIV and Hepatitis B or C testing.
  • Have baseline anti-vaccinia antibody titer < 10.

Exclusion Criteria:

  • Current or anticipated use of other investigational agents or marketed anticancer agent while on study (from the time of enrollment through the time of surgery).
  • Patients who have received chemotherapy or radiotherapy within 4 weeks prior to entering the study.
  • Small pox vaccination for 4 weeks before study therapy and during study treatment.
  • Have received prior gene therapy or therapy with cytolytic virus of any type.
  • Have clinically significant cardiac disease
  • Oxygen saturation <90% measured by pulse oximetry at rest.
  • Receiving concurrent antiviral agent active against vaccinia virus (e.g., cidofovir, vaccinia immunoglobulin, imatinib, ST-246) during the course of study.
  • Have known allergy to ovalbumin or other egg products.
  • Have clinically significant dermatological disorders (e.g., eczema, psoriasis, or any unhealed skin wounds or ulcers)
  • Have a history of allergy to iodinated contrast media.
  • Patients with known brain metastases
  • Pregnant or nursing
  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: NCT02714374

Contacts
Contact: Julie Lewis, CRC, LVN 858-822-4907 jml111@ucsd.edu
Contact: Shakeela Dad, PhD 858-822-5376 sdad@ucsd.edu

Locations
United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Sponsors and Collaborators
Kaitlyn Kelly, MD
Genelux Corporation
Investigators
Principal Investigator: Kaitlyn Kelly, MD University of California, San Diego
  More Information

Responsible Party: Kaitlyn Kelly, MD, Assistant Clinical Professor, University of California, San Diego
ClinicalTrials.gov Identifier: NCT02714374     History of Changes
Other Study ID Numbers: 151060
Study First Received: March 2, 2016
Last Updated: June 17, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by University of California, San Diego:
Oncolytic Virus
Metastatic melanoma
GL-ONC1
Eculizumab
Solid Organ Cancer
Cancer
Surgery
Soliris
Esophageal and gastric adenocarcinoma (Stage III/IV)
Cholangiocarcinoma
Pancreatic adenocarcinoma
Gallbladder cancer
Colorectal cancer (Stage IV)
High-grade mucinous appendix cancer
High-grade gastrointestinal neuroendocrine cancer
Mesothelioma
High-grade soft tissue sarcoma
Stage III or IV

ClinicalTrials.gov processed this record on May 24, 2017